Loading...
HomeMy WebLinkAboutDEQ-CFW_00000640DEQ-CFW 00000640 • • EPA • United States Environmental Protection • Agency • • Sponsored by the Office o Adv • @A June 8- Open June 1 U.S. EPA - Researc Auditorium 109 T.W. Alexand Research Triangle M U.S. EPA PFAA DAYS III SYMPOSIUM OVERVIEW Background The Perfluoroalkyl Acids (PFAAs), such as perflurooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental pollutants of considerable interest to the U.S. Environmental Protection Agency (US EPA) as well as the public. The Office of Pollution Prevention and Toxics (OPPT) and the Office of Water (OW) at US EPA have been actively involved in the health risk assessment of these chemicals. In 2006, US EPA initiated the PFOA Stewardship Program in which eight major companies in the industry committed to voluntarily reduce facility emissions and product content of PFOA and related chemicals on both a domestic and a global basis by 95 percent no later than 2010, and to work toward eliminating emissions and product content of these chemicals by 2015 <http://www.epa.gov/oppt/pfoa/pubs/pfoastewardship.htm>. In 2009, provisional health advisories for PFOA and PFOS in drinking water were issued by OW <http://www.epa.gov/waterscience/criteria/drinking/pha-PFOA PFOS.pdf >. In addition, as part of US EPA's comprehensive approach to enhance the Agency's current chemical management program under the Toxic Substances Control Act (TSCA), action plans have been announced for several chemicals, including the long -chain PFAAs<http://www.epa.gov/oppt/existingchemicals>. These action plans outline the risks that each chemical may present and identify the specific steps the Agency is taking to address those concerns. In the coming years, US EPA will seek formal review and comment on the regulatory actions included in the plans as they are proposed. Over the past several years, investigators from the US EPA Office of Research and Development's (ORD's) National Health and Environmental Effects Research Laboratory (NHEERL), National Exposure Research Laboratory (NERL), National Risk Management Research Laboratory (NRMRL), and National Center for Computational Toxicology (NCCT) have developed research programs to characterize the toxicity of PFAAs, to explore their modes of actions, to develop analytical methods for their detection in various media, to investigate the fate and transport of these chemicals in the environment, and to construct computational models to predict their behaviors. Collectively, they have made significant strides in these research areas. In the summer of 2006, a "PFAA Days" workshop was held at the US EPA campus in Research Triangle Park, NC, where scientists and managers from the Agency's Program Offices and Region Offices met with ORD researchers to identify research needs for health risk assessment. The inaugural meeting was followed by "PFAA Days II" symposium held in June 2008, which was open to the public and attracted about 200 participants from EPA, academia, industry and other governmental entities. A special issue devoted to capture the proceedings and presentations of this symposium was subsequently published in Reproductive Toxicology (vol. 27, issues 3-4, 2009). Goals and Logistics Since the 2008 symposium, significant research progress has been made by the ORD and other scientists with PFAAs, and new findings have been reported in the literature at a rapid pace. Hence, it will be timely to organize another biennial conference on these chemicals. The PFAA Days III symposium to be held on June 8-10, 2010, again on the US EPA campus in Research Triangle Park, NC is designed to review the progress of PFAA research and to share the recent new discoveries. Similar to PFAA Days 11, this informal EPA conference is open to all scientists from other federal and state agencies, chemical industry and academia. However, a main focus of the PFAA Days III meeting is to promote interactions among participants that will lend to future research collaboration. Toward that end, only a few platform presentations are planned, primarily to summarize the state -of -science for the topic of interest. All attendees are encouraged to participate actively through open discussion led by session leaders, as well as poster presentations that highlight findings from individual laboratories. Poster presenters should DEQ-CFW 00000642 submit a brief abstract for review by May 21, 2010 (for questions and detailed information, contact Dr. John Rogers <ropers.lo epa.gov>). Abstracts of platform and poster presentation, conference proceedings and report will be submitted to Reproductive Toxicology for consideration of publication. Two special issues on PFAA research are planned for publication in Reproductive Toxicology and Environmental Science and Technology. Interested authors should contact Dr. Chris Lau (lau.christophera.epa.gov, for Reproductive Toxicology) and Dr. Andy Lindstrom (lindstrom.andrew0epa.gov), Dr. Laurence Libelo (libelo.laurencea-epa.gov) or Dr. Mark Strynar (strynar.marka-epa.gov, for ES&T) for details. A separate session on June 11 will be reserved for EPA scientists and managers to discuss the remaining research needs to support PFAA human health risk assessment. Acknowledgments The symposium was organized by a committee composed of the following members. Christopher Lau, NHEERL/ORD (Chair) John Rogers, NHEERL/ORD (Abstract Review) Barbara Abbott, NHEERL/ORD (Abstract Review) Douglas Wolf, NHEERL/ORD Andrew Lindstrom, NERL/ORD Ross Highsmith, NERL/ORD Marc Mills, NRMRL/ORD Carolyn Acheson, NRMRL/ORD Elaine Francis, ORD Jennifer Seed, OPPT/OCSPP Cathy Fehrenbacher, OPPT/OCSPP Laurence Libelo, OPPT/OCSPP Joyce Donohue, OST/OW The organizers wish to thank Teresa Wall of TAD/NHEERL for her enormous efforts in helping to coordinate the activities of this symposium; David Hollandsworth and Douglas Greene for their invaluable Web site support; Keith Tarpley, John Havel, John Barton, Chuck Gaul, and A.J. Righter for their outstanding efforts in preparing the symposium program, and Ronald Hunter, Kerry Hamilton, and Earlene Walker fur staffiny the on -site registration. 2 DEQ-CFW 00000643 U.S. EPA PFAA DAYS III SYMPOSIUM CALL FOR PAPERS FOR PFAA SPECIAL ISSUES The editors and publishers of the Reproductive Toxicology and Environmental Science & Technology publications have both agreed to publish special focus issues that highlight the materials presented at the U.S. EPA's PFAA Days III Symposium held at Research Triangle Park, NC from June 8 - 10, 2010. Any manuscripts related to poster or platform presentations made at this meeting will be considered for publication in one of these special editions. Research papers related to characterization of PFAA toxicity, elucidation of their modes and mechanisms of actions, description of pharmacokinetics and modeling, epidemiology, and human health risk analysis are encouraged to be submitted to Reproductive Toxicology. Papers for the Environmental Science & Technology focus issue should consider topics that involve fate and transport, reactivity, water and wastewater treatment, risk and exposure assessment in the environmental media, ecological toxicity, epidemiology, human and environmental health. At the time of publication the editors may also include other PFAA-related submissions to compliment the topics covered at the PFAA Days III Symposium. When submitting manuscripts to Reproductive Toxicology or Environmental Science & Technology, authors should indicate in their cover letter that it is intended for the PFAA Days III special focus issue. All manuscripts must be submitted by the end of October 2010 for peer review. Manuscripts accepted for publication will be available on line immediately for both journals. The print edition of the PFAA special issues will be released no later than April 2011 for Reproductive Toxicology and October 2011 for Environmental Science & Technology. For information and questions concerning this call for papers, please contact the guest -editors, Christopher Lau (lau.christopherna.epa.aov, 919-541-5097) for Reproductive Toxicology, and Mark Strynar (strynar.markO.epa.gov, 919-541-3706), Andy Lindstrom (lindstrom.andrewa-epa.gov, 919-541-0551) or Laurence Libelo (libelo.laurencen_epa.gov, 202-564-8553) for Environmental Science & Technology. IN DEQ-CFW 00000644 U.S. EPA PFAA DAYS III SYMPOSIUM AGENDA June 8-10, 2010 U.S. EPA, Research Triangle Park, NC Auditorium C-111 June 8, Tuesday 11:00 AM Registration 1:00 - 1:10 PM Introduction — Chris Lau, TAD, NHEERL, ORD 1:10 - 1:20 Welcoming Remarks — Kevin Teichman, ORD 1:20 - 1:30 Charges of Conference — Elaine Francis, US EPA 1:30 - 5:20 PFAAs in the environment — Session Leaders: Andy Lindstrom (US EPA) and Derek Muir (Environment Canada) 1:30 - 2:15 What's new with PFAAs in the environment? — Scott Mabury (University of Toronto) 2:15 - 2:45 NHANES: PFAAs in US general population — Antonia Calafat (CDC) 2:45 - 3:05 Break 3:05 — 3:35 PFAA distribution in source water and their effective treatment technologies — Shuhei Tanaka (Kyoto University) 3:35 — 4:05 PFAAs in wildlife worldwide — Robert Letcher (Environment Canada) 4:05 — 5:30 Open Discussion Reception in Atrium and/or Focus Group I meeting in Auditorium Focus Group I: PFAA Analytical Chemistry — Group Leaders: Mark Strynar (US EPA), Shoji Nakayama (US EPA), David Ehresman (3M), Mary Kaiser (DuPont) To discuss issues concerning the analysis of perfluorinated compounds: minimum requirements of quality assurance and quality control that make data acceptable. Topics will include assessment of accuracy and precision of a method, demonstration of data reliability at low quantitation levels, inclusion of method/matrix blanks, blank 5:30 - 6:45 matrix spike recovery, use of common reference materials or standards for standardization of methods, potential sources of PFC contamination, and interlaboratory precision. In addition, other issues such as strengths and pitfalls of new analytical techniques (TOF/MS, ion chromatography, total fluorine measurement), ability to analyze a growing number of perfluorinated compounds (on-line SPE, high though -put), modification of analytical equipment for the application to PFC analysis (trap column, removal of LC components) will be addressed. 7:00 Dinner I (optional) at local restaurant June 9, Wednesday 7:45 - 8:20 AM Light breakfast and coffee 8:20 - 8:30 Housekeeping — Chris Lau PFAA exposure — Session Leaders: Laurence Libelo (US EPA) and Kerry Dearfield 8:30 - noon (USDA) 8:30 — 8:50 PFAAs in various environmental media — Mark Strynar (US EPA) 8:50 — 9:10 Environmental -Fate Patterns for PFAAs and their Precursors — John Washington (US EPA) 9:10 — 9:30 PFCs in Consumer Articles — Monitoring the Market Trends — Heidi Hubbard (US EPA) 9:30 — 9:50 Break 67 DEQ-CFW 00000645 June 9, Wednesday (contd.) 9:50 —10:10 PFAAs in waste water treatment plants and sludge — James Kelly (Minnesota Department of Health) 10:10 — 10:30 PFAA exposure to farm cattle — Kerry Deerfield (USDA) 10:30 - 10:50 PFAAs in food and migration from food and packaging — Tim Begley (FDA) 10:50 — 12:00 Open Discussion l Noon - 1:45 PM Poster Session I in Atrium — Environmental PFAAs and Exposure (boxed lunch ) � � 1:45 - 5:30 PFAA epidemiology — Session Leaders: Andrea Pfahles-Hutchens (US EPA) and Geary Olsen (3M) 1:45 — 2:00 A brief overview of PFAA epidemiology — Geary Olsen (3M) The C8 Science Panel Program and findings from cross sectional analyses of C8 and 2:00 — 2:25 clinical markers in the Mid -Ohio Valley population — Tony Fletcher (London School of Hygiene and Tropical Medicine) Retrospective Exposure Analysis and Predicted Serum Concentrations of PFOA in the 2:25 — 2:45 Ohio River Valley — P. Barry Ryan (Emory University) 2:45 — 3:00 Open Discussion 3:00 — 3:20 Break PFAAs and C8 study with Type II diabetes, uric acid, and lipids — Kyle Steenland 3:20 — 3:40 (Emory University) PFOA and Heart Disease: Epidemiologic Studies of Occupationally Exposed 3:40 — 4:00 Populations — J. Morel Symons (DuPont) 4:00 — 4:25 Open Discussion on toxicological findings versus epidemiological reports PFAAs and reproductive/developmental endpoints, pregnancy outcomes in C8 and 4:25 — 4:45 other community health studies, methodological considerations and future research — Cheryl Stein (Mount Sinai School of Medicine) PFAAs and pregnancy outcomes in general population studies, methodological considerations, 4:45 — 5:05 physiology of pregnancy considerations and future research — Matthew Longnecker (NIEHS) 5:05 — 5:30 Open Discussion Social Hour in Atrium, and/or Focus Group II meeting in Auditorium Focus Group II: PFAA Issues Among Governmental Agencies — Group Leaders: Andy Lindstrom (US EPA), Tony Krasnic (US EPA), Gail Mitchell (US EPA), Graham White (Health Canada) To provide an informal venue for networking among risk assessors and other specialists from various regulatory agencies in US (Regions, States, local) and other countries concerning issues they currently face with PFAAs. Participants are 5:30 - 6:45 invited to share their experience, questions and research needs relating to: PFAA sources, presence in environmental media, transport between and within media, relationships between various media (e.g. soil to water, surface water to drinking water); organizing environmental monitoring surveys; laboratory analysis options; commercial analytical services; development of toxicological end points for regulation and remediation, remediation approaches, health advisory levels; organizing comprehensive management policies; and emerging issues of interest. 7:00 Dinner Il (optional) at local restaurant June 10, Thursday 7:45 - 8:20 AM Light breakfast and coffee 8:20 - 8:30 Housekeeping — Chris Lau 8:30 - Noon PFAA toxicities — Session Leaders: Jennifer Seed (US EPA) and John Butenhoff (3M) [1 DEQ-CFW 00000646 8:30 — 9:00 An overview of PFAA pharmacokinetics — Harvey Clewell (Hamner Institute) 9:00 — 9:30 Organic anion transporters and PFAA tissue distribution — Bruno Hagenbuch (Univeristy of Kansas) 9:30 — 9:50 Break 9:50 — 10:20 Translating toxicological information on perfluoroalkyls for human risk assessment — John Butenhoff (3M) 10:20 — 10:50 PFAA ecotoxicity — John Newsted (Michigan Sate University) 10:50 — 12:00 Open Discussion Noon -1:45 PM Poster Session II in Atrium — PFAA Toxicity, Modes of Action and Epidemiology (boxed lunch provided) 1:45 - 5:15 Nuclear receptor involvement in PFAA actions — Session Leaders: Chris Corton (US EPA), Cliff Elcombe (CXR Biosciences) 1:45 — 2:00 A brief overview of PFAA modes of action — Chris Corton (US EPA) 2:00 — 2:30 PPAR involvement in PFAA development toxicity — Barbara Abbott (US EPA) 2:30 — 3:00 Nuclear receptor involvement in PFAA-induced metabolic changes — Mitch Rosen (US L''�) 3:00 = 3 20 EPA) Break 3:20 — 3:50 PPAR involvement in PFAA immunotoxicity — Jaime DeWitt (East Carolina University) 3:50 — 5:15 Open Discussion on PFAA toxicity and modes of action, and their relevance to epidemiological findings 5:15 - 5:30 Closing remarks — Elaine Francis (US EPA) 5:30 Conference adjourned 7 DEQ-CFW 00000647 U.S. EPA PFAA DAYS III SYMPOSIUM BIOGRAPHICAL SKETCHES Barbara Abbott Barbara Abbott is a Senior Researcher in the Developmental Toxicology Branch of the Toxicity Assessment Division, of the National Health and Environmental Effects Research Laboratory of the US Environmental Protection Agency. She received a Ph.D. and M.S. in Toxicology at NC State University in 1985 and was a post -doctoral fellow at NIEHS. Dr. Abbott studies the mechanisms of developmental toxicity with particular emphasis on receptor -mediated pathways. Dr. Abbott has an extensive publication record and has received five EPA Scientific and Technological Achievement Awards. Dr. Abbott is a member of the Teratology Society and the Society of Toxicology. She served as President of the North Carolina Chapter of the SOT in 2002 and as Councilor for the Reproductive and Developmental Specialty Section of the SOT. Dr. Abbott is an Associate Editor for Toxicological Sciences. Timothy H. Begley Tim Begley is currently the Chief of the Methods Development Branch, Division Analytical Chemistry, Office of Regulatory Science, CFSAN, US Food and Drug Administration. As Chief of the Methods Development Branch at FDA, he over sees the research of 15 scientists working on analytical methods development for determining direct food additives, migration from food packaging, chemical contaminants such as pesticides in food and food adulteration. Tim Begley has been a research manager and researcher with FDA for 26 years in the area of developing analytical methods for chemical contaminants and additives in foods. He is the author or coauthor of over 40 publications and book chapters. John L. Butenhoff John Butenhoff is a Corporate Scientist in Toxicology within the Medical Department of 3M Company. He has led toxicological and toxicokinetic research, as well as health risk assessment programs associated with fluorochemicals produced by 3M. He received his A.B. in Biology from Franklin and Marshall College, Lancaster, PA and his M.S. in Occupational Health and Ph.D in Toxicology from the University of Minnesota. Dr. Butenhoff is currently an adjunct professor in the graduate program in Toxicology at the University of Minnesota and holds professional board certifications by the American Board of Toxicology and the American Academy of Industrial Hygiene. He has contributed to over fifty papers and numerous presentations on the toxicology of perfluoroalkyl acids. Antonia Calafat Antonia Calafat serves as Chief of the Personal Care Products Laboratory at the Division of Laboratory Sciences, National Center for Environmental Health (NCEH) of the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. She earned her Bachelor, Masters and Doctoral degrees in Chemistry from the University of the Balearic Islands in Spain. Prior to her career at CDC, she was a Fulbright Scholar and a Research Associate at Emory University. Since starting her tenure at CDC in 1996, Dr. Calafat has been involved in developing, validating, and applying analytical methods for measuring, in biological matrices, environmental chemicals including volatile organic compounds, disinfection - byproducts, chemical warfare agents, and phytoestrogens. She currently leads several active research programs for assessing human exposure to chemicals added to consumer and personal -care products such as phthalates, environmental phenols (e.g., bisphenol A, triclosan, parabens), and polyfluoroalkyl compounds. Dr. Calafat has developed and maintained extensive collaborative research with leading scientists in the fields of exposure science, epidemiology, toxicology and health assessment, and has authored or co-authored over 150 peer -reviewed publications. Her research has made relevant contributions to CDC's biomonitoring program including the CDC's National Reports on Human Exposure to Environmental Chemicals. E DEQ-CFW 00000648 Harvey Clewell Harvey Clewell is the Director of the Center for Human Health Assessment at the Hamner Institutes for Health Sciences. He is a leading expert on the use of tissue dosimetry and mode -of -action information in chemical safety and risk assessment. He has gained an international reputation for his research on the application of Physiologically Based Pharmacokinetic (PBPK) modeling to chemical risk assessment and pharmaceutical safety assessment, having played a major role in the first uses of PBPK modeling by FDA, ATSDR, OSHA, and EPA. He has developed PBPK models for a wide variety of applications, including both environmental compounds and drugs. He has a Masters in Chemistry from Washington University, St. Louis, and a PhD in Toxicology from the University of Utrecht. His current research focuses on the application of PBPK modeling for in vitro to in vivo extrapolation of cell -based toxicity assays, the incorporation of genomic dose -response information in quantitative risk assessment, and the application of systems biology methods to understand drug induced liver toxicity. Chris Corton Chris Corton is a Senior Research Biologist in the Systems Biology Branch of the Integrated Systems Toxicology Division within the National Health and Environmental Effects Research Laboratory, under the Office of Research and Development of the U.S Environmental Protection Agency. He received his Ph.D. degree in Biochemistry from University of Kansas Medical Center followed by a post -doctoral research fellowship at Duke University. His main area of research is nuclear receptor mode of action. He is currently the NHEERL leader of the EPA Virtual Liver project directed towards mode of action prediction and quantitative models of liver toxicity after exposure to environmentally -relevant chemicals including perfluorinated compounds. His research interests also include predicting life stage susceptibility and the use of toxicogenomics to predict mode of action and human relevance. Kerry Dearfield Kerry Dearfield is currently the Scientific Advisor for Risk Assessment in the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). There in the Office of Public Health Science, he develops policies, guidance, and directions for risk assessments and advises on environmental and microbial risk assessments for food safety. Dr. Dearfield has published extensively in numerous peer reviewed publications on genetic toxicology of chemicals, genotoxicity in regulatory decisions and guidelines, peer review and risk assessment practices, and science policy issues. His scientific interests include the development of science policy and guidance; health risk assessments of environmental and microbial food contaminants; modes of action for toxicity (including mutational, physiological and pharmacological mechanisms); use of genotoxicity data in regulatory decisions (heritable risk, carcinogenicity, general toxicity); health effects testing guidelines (e.g., carcinogenicity, mutagenicity); development and use of peer review; and, risk assessment, risk management, and risk communication issues. Prior to his current position, Dr. Dearfield worked for over two decades at the Environmental Protection Agency as a risk assessor and Senior Scientist for Science Policy. He earned his BS degree (Biology) from the College of William and Mary, his MS degree (Cell Biology) from the University of Pittsburgh, and his doctorate (Pharmacology) from the George Washington University Medical Center. Jamie DeWitt Jamie DeWitt received her B.S. degree in Biology and Environmental Science from Michigan State University and her Ph.D. in Environmental Science and Neural Science from Indiana University - Bloomington. She completed a brief postdoc in wildlife cardiotoxicology at Indiana University and then moved to North Carolina for a postdoc in immunotoxicology at the U.S., Environmental Protection Agency through a cooperative training agreement with the University of North Carolina. Jamie is currently an assistant professor in the Department of Pharmacology and Toxicology at the Brody School of Medicine at East Carolina University. Her current research focus is on developmental neuroimmunotoxicological effects of environmental agents and her laboratory is concentrating on the role of immunopathogenesis in neurodevelopmental diseases. 10 DEQ-CFW 00000649 Cliff Elcombe Cliff Elcombe is co-founder and Technical Director of CXR Biosciences, as well as a Senior Lecturer in the Biomedical Research Centre, University of Dundee Medical School. Prior to founding CXR, Cliff joined the University of Dundee in February 1997 after an 18-year career at Zeneca's (formerly Imperial Chemical Industries) Central Toxicology Laboratory in Cheshire, England, where he was a Senior Scientist in Investigative Toxicology. Dr. Elcombe's research interests are focused on understanding mechanisms of target organ toxicity thereby facilitating scientifically -based risk assessment. Dr. Elcombe received his BSc and PhD in biochemistry from the University of Surrey and was awarded the European Society of Toxicology's young scientist award in 1984. Dr Elcombe is the author or co-author of over 100 peer -reviewed publications and has served on several national and international advisory committees. Tony Fletcher Tony Fletcher is Senior Lecturer in Environmental Epidemiology at the Department of Social and Environmental Health Research in the London School of Hygiene & Tropical Medicine (LSHTM) and Adjunct Research Professor in Environmental Health in the School of Public Health, Boston University, Massachusetts, USA. He has worked in environmental and occupational epidemiology and risk assessment for 30 years, including several years at the International Agency for Research on Cancer in Lyon, France. He was President of the International Society for Environmental Epidemiology for the years 2004-5, he has managed major European research grants and is a Member of the "C8 Science Panel" responsible for designing and implementing a study of potential health effects of drinking water exposure to Perfluorooctanoic acid (PFOA or C8), in West Virginia and Ohio, USA. Elaine Francis Elaine Francis is the National Program Director for the U.S. Environmental Protection Agency's Pesticides and Toxics Research Program. She coordinates the development and implementation of multi -million dollar intramural and extramural research programs, working with scientists from across EPA, other federal agencies, governments of other countries, academia, and the regulated scientific community. The research programs she oversees include those on endocrine disruptors, agricultural biotechnology, and the development of testing, risk assessment, and risk management approaches for pesticides and toxic substances — including perfluorinated chemicals. Elaine has been at EPA for almost 30 years. She spent 1991 as a legislative fellow to Senator Joseph Lieberman of Connecticut working on pesticides, lead, and children's issues. She received her doctorate in Anatomy from Thomas Jefferson University in Philadelphia, from which she received the Distinguished Alumni Award in 2001. Dr. Francis is the recipient of numerous awards at EPA, including one gold, one silver, and twelve bronze medals. Bruno Hagenbuch Bruno Hagenbuch (Professor) earned his Ph.D. from the Federal Institute of Technology in Zurich in 1986, did a postdoctoral fellowship at UCLA, and returned to Zurich. During his work in the Division of Clinical Pharmacology and Toxicology at the University Hospital he discovered the bile acid uptake transporter (NTCP) and was involved in the identification and characterization of organic anion transporting polypeptides (OATPs), important drug uptake transporters of hepatocytes. He joined the University of Kansas Medical Center in 2005 as a full professor and is conducting research examining the roles of NTCP and OATPs in the hepatic uptake of drugs and environmentally persistent polyfluorinated compounds. He has a NIH-R01 grant, and has published 96 peer -reviewed manuscripts and reviews. Heidi Hubbard Heidi Hubbard is a researcher at the US Environmental Protection Agency in the National Risk Management Research Laboratory. Her research is focused on measuring perfluorinated compounds in consumer products and indoor environments to develop realistic exposure scenarios. Before coming to NRMRL, Dr. Hubbard worked as a post-doc in EPA's National Exposure Research Laboratory developing analytical methods to measure endogenous human biomarkers for the purpose of exposure reconstruction. Prior to working at the EPA, Dr. Hubbard received a Bachelor's degree from Purdue University and a Masters and PhD in environmental engineering from the University of Texas with a focus on indoor air chemistry. 11 DEQ-CFW 00000650 James Kelly James Kelly received a Bachelor of Science degree in environmental and public health from the University of Wisconsin -Eau Claire in 1987, and a master of science in environmental health from the University of Minnesota in 1989. He is currently a research scientist at the Minnesota Department of Health, Environmental Health Division, Site Assessment & Consultation Unit. His responsibilities include preparing public health assessments and health consultations on state and federal Superfund sites, dump sites, and industrial facilities. Other duties include researching the health effects from exposure to hazardous chemicals in the environment, with a current emphasis on perfluorochemicals. Another focus of his work has been assessing the health risks from environmental exposure to subsurface vapors. Christopher Lau Christopher Lau is Lead Research Biologist and Acting Chief in the Developmental Toxicology Branch of Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, under the Office of Research and Development of the U.S, Environmental Protection Agency. He received his Ph.D. in Pharmacology from Duke University. He is an active member of the Society for Neuroscience, Society of Toxicology, Teratology Society, and International Society for Developmental Origins of Heath and Diseases. His research interests include developmental toxicology, teratology, and risk assessment modeling. Robert Letcher Robert Letcher is Research Scientist and Head of Environmental and Analytical Chemistry Research at the National Wildlife Research Center, Toxicology and Disease Division, Wildlife Landscape and Science Directorate, Science and Technology Branch of Environment Canada. Presently, he is Adjunct Professor of Chemistry and Biochemistry at Carleton University, Adjunct Professor of Great Lakes Institute for Environmental Research at University of Windsor, Associate Research Faculty of Environmental Biology at University of Guelph, Associate Coordinator of Ottawa -Carleton Chemical and Environmental Toxicology Program, and Vice -President of International Association of Great lakes Research. He received his B.Sc. in Chemistry from University of Toronto, M.Sc. in Chemistry and Ph.D. in Environmental Chemistry and Ecotoxicology from Carleton University. His research interests encompass environmental and analytical chemistry, spatial and temporal trend biomonitoring, toxicology (e.g., both endocrine and immune related), and the effects of anthropogenic chemicals in the environment. Research activities focus on persistent and bio-accumulative organohalogens as well as other established and emerging organic chemicals of concern in aquatic environments. Examples of emerging contaminants of concern include brominated flame retardants, perfluorinated alkyl substances, pesticides, herbicides, pharmaceuticals, and personal care products. Laurence Libelo Dr. Libelo is a Senior Environmental Engineer in the EPA's Exposure Assessment Branch in the Office of Chemical Safety and Pollution Prevention where he works on environmental fate and transport and exposure issues for new and existing chemicals. Prior to joining EPA he conducted basic and applied research on environmental contamination and remediation in groundwater and surface water at the U.S. Air Force Research Laboratory. He has been involved in trying to understand PFC occurrence and behavior since the mid 1990s. He holds a degree in Geology from the University of Maryland, A M.S. in Environmental Science and Engineering from Virginia Tech and a Ph. D. in Marine Science with an emphasis on contaminant geochemistry and groundwater/surface water interactions from the College of William and Mary. 12 DEQ-CFW 00000651 Andrew B. Lindstrom Andrew B. Lindstrom is an environmental scientist with the United States Environmental Protection Agency's (USEPA) National Exposure Research Laboratory (NERL) in Research Triangle Park, North Carolina. He is currently conducting methods development research for the Exposure Measurements and Analysis Branch where his areas of expertise include: measurement of persistent perfluorinated compounds (PFCs), use of protein adducts as indicators of exposure to carcinogens, and analysis of exhaled alveolar breath to determine exposure and dose of volatile organic compounds (VOCs). He has considerable experience with gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) analysis to measure trace level contaminants in biological and environmental media. Matthew P. Longnecker Matthew P. Longnecker is a Senior Investigator in the Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, U.S.A. Dr. Longnecker graduated from Antioch College and Dartmouth Medical School, completed a residency in internal medicine at Temple University Hospital, and then got a doctorate in epidemiology from Harvard School of Public Health. He was an Assistant Professor of Epidemiology at UCLA School of Public Health before joining NIEHS in 1995. He has authored over 145 articles in peer -reviewed journals, and is on the editorial board of the American Journal of Epidemiology, Epidemiology, and Environmental Research. He has served as a Deputy Editor and is now a member of the Advisory Board of Environmental Health Perspectives. Dr. Longnecker's research program at present is focused on the health effects of early -life exposure to environmental contaminants. He has ongoing projects to examine the effects of DDT, bisphenol A, and organophosphate pesticides. These projects are being conducted in Africa, Mexico, the Netherlands, and Norway. Scott A. Mabury Scott Mabury received his undergraduate degree in chemistry from Northland College in 1984, after which he spent a few years as a Peace Corps Volunteer on the island of Mindoro in the Philippines. He received his Ph.D. in Environmental Chemistry from the University of California -Davis in 1993 under the mentorship of Dr. Donald Crosby. He joined the faculty in chemistry at the University of Toronto in 1995 and rose to the rank of Professor in 2005. He has served as Associate Chair for Undergraduate (2002- 2003), Chair of Chemistry (2003 to 2009) and Vice -Provost Academic Operations (2009-present) at the University of Toronto; as well as Visiting Professor at University of the Philippines-Diliman (2002). He has been honored with four teaching awards, a Premier's Research Excellence Award and an Alumni Award from his alma mater. Dr. Mabury's research has focused on the role the fluorine atom plays in the fate, disposition, and persistence of fluorinated pesticides, pharmaceuticals, consumer and industrial products. Derek Muir Derek Muir is Senior Research Scientist at Environment Canada (EC) and Chief of the Priority Substances Exposure (PSEx) Section within the Aquatic Ecosystem Protection Research Division, Science and Technology Branch of Environment Canada. His major research interests center on understanding bioaccumulation and bioavailability of persistent chemicals in the aquatic and terrestrial environments under field and laboratory conditions with special emphasis on food chain transfer. As Senior Scientist, Dr. Muir's role also includes leading projects under EC's Chemical Management Plan and Clean Air Regulatory Agenda involving PSEx scientists, EC scientists from other Directorates, and University collaborators. Dr. Muir provides advice and data to the Science and Risk Assessment Directorate of EC on new and existing chemicals and on pesticides to the Pesticide Management Review Agency of Health Canada. For the past 15+ years, he has a major role in leading the preparation of assessments of spatial and temporal trends of contaminants in the Canadian Arctic for Indian and Northern Affairs Canada and in the circumpolar Arctic for the Arctic Monitoring and Assessment Program. He ha also contributed to Great Lakes State of the Environment assessments. Dr. Muir received his B.Sc. in Chemistry, M.Sc. and Ph.D. in Agricultural Chemistry from McGill University. He is currently Adjunct Professor of Environmental Biology at University of Guelph, Adjunct Professor of Chemistry at University of Toronto and Editor for Environmental Toxicology and Chemistry. 13 DEQ-CFW 00000652 John Newsted John Newsted is a Senior Project Scientist at Entrix, Inc and an Adjunct Professor in the Department of Animal Science at Michigan State University. Dr. Newsted received his PhD. In Environmental Toxicology (1991) from Michigan State University; his M.S., Biology (1985) from Michigan Technological University; and his B.S., Limnology (1978) from Michigan State University. Dr. Newsted has over 15 years of experience and has worked in academia, industry and as a consultant in ecotoxicology. Dr. Newsted's expertise is in studing the fate and effects of organic and inorganic chemicals in aquatic and terrestrial environments. He is active in the development of biochemical and molecular indicators of exposure, effect and susceptibility in aquatic and terrestiral organisms and in the conduct of environmental risk and hazard assessment. He has conducted research to evaluate the fate and effect of persistent, chlorinated chemicals including polychlorinated biphenyls, dioxins and organochlorine pesticides on aquatic and terrestrial organisms. His current research interests include the development and validation of in vitro and in vivo model systems to identify and classify potential endocrine disrupting chemicals, the development and validation of an avian dioxin sensitivity model for dioxin -like compounds, the development and use of a unique jaw lesion as a biomarker of effect for Ah receptor agonists in mink. He is also actively involved in the study of the distribution, fate, and effect of fluorochemicals in aquatic and terrestrial systems. Newsted has published more than 80 papers and review articles in his field of expertise. Geary W. Olsen Geary Olsen is a staff scientist in the Medical Department at the 3M Company (St. Paul, MN). He has a D.V.M. from the University of Illinois, College of Veterinary Medicine and a Ph.D. in epidemiology from the University of Minnesota, School of Public Health. His major research areas have involved epidemiologic investigations of 3M perfluorochemical manufacturing employees and a series of biomonitoring studies of 3M workers and American Red Cross adult blood donors. He is an author or co-author of more than 30 perfluorochemical-related publications in the scientific literature. Andrea Pfahles-Hutchens Andrea Pfahles-Hutchens is an Epidemiologist in the Risk Assessment Division of the Office of Chemical Safety and Pollution Prevention of the U.S. Environmental Protection Agency in Washington, DC. She has been employed by EPA for over 15 years and has been working on issues related to perfluorochemicals for over 10 years. Andrea also provides technical support to EPA on epidemiology issues related to chemicals such as lead, formaldehyde, diisocyanates, and polybrominated diphenyl ethers and is the Office point of contact for biomonitoring issues. She holds a bachelor's degree from The Pennsylvania State University and a master's of science degree in Epidemiology from the University of Cincinnati. Mitchell Rosen Mitchell Rosen is Research Biologist with the U.S. Environmental Protection Agency in the Research Triangle Park, North Carolina. His position is affiliated with the Systems Biology Branch of the Integrated Systems Biology Division, part of the National Health and Environmental Effects Research Laboratory under the Office of Research and Development. He received his Ph.D. degree in Physiology from North Carolina State University. He is a member of the Society of Toxicology and the Society of Developmental Biology. His research involves the use of molecular techniques to evaluate mechanisms associated with reproductive toxicants. 14 DEQ-CFW 00000653 Barry Ryan P. Barry Ryan is Professor of Exposure Assessment and Environmental Chemistry in the Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University. He is jointly appointed in the Department of Chemistry at Emory University as well. Prior to joining the faculty at Emory he was on the faculty at Harvard School of Public Health. He received a BS in Chemistry from the University of Massachusetts, an MS in Physical Chemistry from the University of Chicago, and doctorate in Computational Chemistry from Wesleyan University. He has been active in the exposure assessment field for 30 years publishing in excess of 95 peer -reviewed manuscripts and book chapters. His work has included both cross -sectional and longitudinal studies of community -based exposure for multiple pollutants in multiple media. Dr. Ryan serves on the Federal Advisory Committee for the National Children's Study being undertaken by the National Institutes of Health. Jennifer Seed Jennifer Seed is Deputy Division Director of the Risk Assessment Division within the Office of Chemical Safety and Pollution Prevention of the U.S. EPA. She has been the lead for the Agency's hazard and risk assessment activities of PFOA and other perfluorinated compounds for the last 11 years. She has also been the lead for the international assessments of PFOS and PFOA under the auspices of the OECD. In addition, she is a member of the Agency's Risk Assessment Forum, and has been involved in numerous risk assessment activities both domestically and internationally. Dr. Seed received a PhD in developmental biology from the University of Washington. Kyle Steenland Kyle Steenland is an epidemiologist, and a Professor in the Dept of Environmental Health at the Rollins School of Public Health at Emory U, where he has worked since 2002. Prior to that time he worked for 20 years for NIOSH doing occupational epidemiology. He is part of a three -person C8 Science Panel which is conducting a series of studies in the mid -Ohio valley to determine whether PFOA (or C8) is linked to any disease. The Science Panel was created pursuant to a 2004 settlement of a lawsuit between community residents and Dupont, and is independent of either party to that lawsuit. Cheryl R. Stein Cheryl R. Stein, PhD is a perinatal epidemiologist at Mount Sinai School of Medicine in New York, NY. Since 2007 she has been working with Dr. David Savitz, a member of the C8 Science Panel, on the reproductive and child development studies of the C8 Health Project. The C8 Science Panel is conducting a series of studies in the Mid -Ohio Valley to determine whether PFOA (aka C8) is linked to any disease. The Science Panel was created pursuant to a 2004 settlement of a lawsuit between community residents and DuPont, and is independent of either parry to that lawsuit. Mark Strynar Mark Strynar is a Physical Scientist in the Methods Development and Application Branch of the Human Exposure and Atmospheric Sciences Division, within the National Exposure Research Laboratory, under the Office of Research and Development of the U.S, Environmental Protection Agency. He received his Ph.D. degree in Soil Science from The Pennsylvania State University, his Masters degree from Texas A&M University and his Bachelors degree from The University of Rhode Island. His research interests include analytical chemistry and the fate and transport of perfluorinated compounds environmental media. 15 DEQ-CFW 00000654 J. Morel Symons J. Morel Symons holds a bachelor's degree in biology from the University of Virginia, a Master of Public Health from Emory University, and a doctorate in epidemiology from Johns Hopkins University. He completed his dissertation under the supervision of Dr. Jonathan Samet. His research focused on the adverse health effects of fine particulate matter air pollution for persons with congestive heart failure. During his doctoral studies, he was a research analyst for projects evaluating the health impact of the 1990 Gulf War, air pollutant exposures at the World Trade Center disaster site, respiratory illnesses and symptoms in children in North Dakota, and has contributed to the design and conduct of epidemiologic and exposure studies of air pollutants in Baltimore, Maryland. He is a visiting professor of epidemiology and environmental health risk assessment at the University of Pretoria, South Africa, and has been a visiting lecturer in epidemiology at the American University in Armenia. Currently, he is an epidemiologist at the DuPont Haskell Global Centers for Health and Environmental Sciences where he researches occupational and community health associated with the manufacturing facilities and processes of E.I. du Pont de Nemours Company. Shuhei Tanaka Shuhei Tanaka received a doctoral degree in engineering from Ritsumeikan University (Kyoto) in 2003, and went on to do post -doctoral work at the Kyoto University's Research Center for Environmental Control. He soon became an assistant professor at Kyoto University's Research Center for Environmental Management, and has recently advanced to associate professor with the University's Graduate School of Global Environmental Studies. Dr Tanaka's current research is focused on the transport, fate, and control of PFAAs in aquatic systems. His research has mainly been conducted in the developing Southeast Asia region, but he has also traveled and worked in Europe and North America. In addition to his research on the perfluorinated compounds, he has done extensive work with the Lake Biwa region of Japan, investigating engineering and phytoremediation strategies to preserve and rehabilitate the fragile freshwater resources of central Japan. Kevin Teichman Kevin Teichman is the Deputy Assistant Administrator for Science in the Office of Research and Development (ORD). He served as the Acting Science Advisor to the EPA from January through December of 2009. He previously served as the Director of the Office of Science Policy (OSP) within ORD. In this capacity, he coordinated ORD participation in EPA's policymaking in all media (air, water, waste, pesticides and toxic substances) to ensure these policies reflected sound science. In addition, he helped lead the planning of EPA's research program, striving to ensure the research program responded to the needs of EPA's Program and Regional Offices and maintained its leadership role in the environmental research community. Dr. Teichman has B.S. and M.S. degrees from the Massachusetts Institute of Technology and a Ph.D. degree from the University of California at Berkeley, all in Mechanical Engineering. John Washington John Washington received a Ph.D. in geochemistry at Penn State. He worked for about ten years in a geological consulting firm in State College, PA, first as a Senior Geochemist and finishing at the firm as a vice president. John then moved to the USEPA National Exposure Research Laboratory in Athens, GA where he conducts research as a Research Chemist. For several years, he conducted research on controls on redox processes in environmental systems. For the last few years, John has conduced research primarily on synthetic fluorinated compounds. At the EPA/Athens laboratory, John collaborates on this research with Dr. Jackson Ellington, Dr. Tom Jenkins, Dr. Hoon Yoo and Dr. John Evans who passed away recently. John is married and has two children, a rising high-school senior and a rising University of Georgia freshman. 16 DEQ-CFW 00000655 U.S. EPA PFAA DAYS III SYMPOSIUM ABSTRACTS 01—What's New with PFAAs in the Environment? Scott A. Mabury Department of Chemistry, University of Toronto, Ontario, Canada It's been recognized for —10 years that perfluorinated acids (PFAs including carboxylates/sulfonates) are widely disseminated in the global environment and appear at high concentrations in humans and in Arctic mammals; a newly recognized PFA is the perfl uorophos phonic acid or PFPAs, were recently discovered in our lab. Earlier work indicated residual fluoro-alcohols were significant (a few %) in fluorinated Il,o- polymers and surfactants (food contact paper coatings) and likely contributed significantly to F O_ the historical burden globally of PFAs. These fluoroalcohols are also readily found in the F F atmosphere and have been shown to undergo atmospheric transport and OH driven F F transformation reactions to yield the observed perfluorinated acids. Model studies suggest F F significant production of these acids in remote Arctic regions have been confirmed by flux F F measurements into the ice cap. Overall, extensive work indicates essentially any perfluorinated F alyl group containing a reactive functionality appears to yield PFCAs through atmospheric F reaction and processing. Some chemicals are surprising sources of PFCAs including the ketone F F shown which will readily photolyze to form PFPA (not surprising) but will also hydrolyze, in the F F dark, to form the same PFA (surprising to us anyway). Recent experiments have shown the F F ester and phosphate esters of FTOH based monomers and surfactants are readily hydrolyzed through microbial and mammalian metabolism. We have discovered relatively high CF3 concentrations of diPAPs, a phosphate based polyfluorinated surfactant, in CF2� �c F human blood. The building block fluoro-alcohols and the surfactants F3C C \ themselves are readily metabolized, via reactive intermediates, to the 11 CF3 resulting PFCAs. Some of these intermediates have been shown to be highly toxic to D. O Magna (ie 10:2 FTCA) or readily react with GSH (the acrylic aldehydes). Human contamination is suggestive of an indirect source of exposure through metabolism of the fluorinated alcohols, which would indicate attention to the reactive intermediates is prudent. Of significant interest is whether the large production volume fluorinated polymers themselves are a source of PFA; recent success in overcoming the inherent analytical challenges of probing the fluorinated polymers themselves indicates they are labile under typical environmental conditions. 02—Serum Concentrations of Polyfluoroalkyl Chemicals in the General U.S. Population: Data from the National Health and Nutrition Examination Survey (NHANES) Calafat AM, Kato K, Kuklenyik Z, Wong L-Y, Caudill SP, and Needham LL Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA Polyfluoroalkyl chemicals (PFCs) have been used worldwide for more than 50 years in the production of polymers that provide fire resistance and oil, stain, grease, and water repellency. These polymers are used in the textile, automotive, building/construction, chemical processing, aerospace, electronics, and semiconductors industries. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are two widely studied PFCs. The interest in PFOS and PFOA stems from their known animal toxicity, their bioaccumulative potential and global presence, and their persistence in humans, wildlife, and the environment. Biomonitoring programs are useful for investigating human exposure to PFCs and other environmental chemicals. One of these programs, the National Health and Nutrition Examination Survey (NHANES), conducted annually in the United States by the Centers for Disease Control and Prevention, is designed to collect data on the health and nutritional status of the noninstitutionalized, civilian U.S. population. We have analyzed serum from participants of several NHANES by on-line solid -phase 17 DEQ-CFW 00000656 extraction coupled to isotope dilution -high performance liquid chromatography -tandem mass spectrometry to assess exposure to PFOS, PFOA, and other PFCs in the U.S. general population. We will discuss the usefulness of biomonitoring, using NHANES as example, to provide evidence of exposure and absorption of PFCs in humans and to assess temporal changes in internal dose as a result of changes in manufacturing practices, including the phase -out of PFOS and related materials based on perfluorooctanesulfonyl fluoride in 2000-2002. 03—PFAA Distribution in Source Water and Their Effective Treatment Technologies Shuhei Tanaka,' Shigeo Fujii,' Chinagarn Kunacheva,' Stm/d. Senevirathna, I Koji Kimura,' and Norimitsu Saito' 'Graduate School of Global Environmental Studies, Kyoto University; 2 RIEP of Iwate Prefecture, Japan Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) distribution are reported in source water of 25 cities in 10 countries (i.e., Japan, Singapore, Thailand, Malaysia, China, Vietnam, Taiwan, Sweden, Turkey and Canada). More than 1,300 samples were collected in different water environments (e.g., river, lake, wetland, reservoir, wastewater treatment plant, residence, and sea) from Nov. 2004 to Dec. 2009. The main conclusions obtained in this study are as follows: 1) The average concentration of PFOS in the surface water of rivers was more than 10.0 ng/L in Osaka. The average concentration of PFOS in residential tap water was more than 10.0 ng/L in Bangkok and Taipei. 2) The average concentration of PFOA in the surface water of rivers was more than 1,000 ng/L (median : 48.6 ng/L) in Osaka, and it was more than 15 ng/L in Kyoto, Shenzhen, Khon Kaen, and Singapore. The average concentration of PFOA in residential tap water was more than 10 ng/L in Osaka and Okayama in Japan. 3) The number of cities where the difference between river water and tap water was less than 1.0 ng/L in the median concentrations of dissolved PFOS and PFOA was 16 for PFOS and 11 for PFOA, respectively. 4) The dissolved PFOS and PFOA concentrations in effluent were higher than those in influent of most wastewater treatment plants (16/19 for PFOS, 38/45 for PFOA). Combined coagulation / filtration technologies were applied for PFAAs removal from wastewater. Three conventional inorganic coagulants and six cationic organic coagulants were tested by a series of jar tests. It was determined that relatively high coagulant dose of 200 pL/L of organic coagulant was needed for the optimum elimination of PFAAs at 10 pg/L. Jar test results with PFOA showed that polymer type cationic organic coagulates were 40 % better than conventional inorganic coagulants. Jar test with mixture of PFAAs showed that long chain PFAAs can be easily coagulated than short chain PFAAs. The optimum molecular weight of cationic organic polymer for PFAAs elimination was identified as 100,000 Da. Jar test results with PFAAs spiked wastewater showed that other organic matters encourages PFAAs coagulation by organic coagulants for long chain and medium chain PFAAs. 04—Perfluoroalkyl Acids (PFAAs) in Wildlife and Fish Worldwide Robert J. Letcher Wildlife Toxicology Research Section, Ecotoxicology and Wildlife Health Division, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario, Canada Various perfluoroalkyl acids (PFAAs) and their polyfluorinated precursor compounds have been industrially manufactured for over 50 years, although what is actually produced has been in a state of flux in recent years, e.g. recent phase -outs of PFAA chemistries with C8 chain lengths. Regardless, the global production of various PFAAs is in the order of thousands of tons per year. PFAAs are used in various industrial and consumer products such as fluorinated polymers, surfactants, insecticides, and aqueous fire -fighting foams. Numerous PFAAs are considered to be terminal products with respect to degradation, shown to be bioaccumulative contaminants, and continue to be a global environmental issue. Perfluorinated sulfonates (PFSAs) and carboxylic acids (PFCAs), and their precursors have been reported in tissues or eggs of various (global) populations of wildlife, including birds and mammals as well as in fish. PFCAs and PFSAs have bioaccumulative properties and biomagnify in the aquatic food web, resulting in the highest exposure in top predator species. Over the last decades, concentrations of PFSAs (and in particular perfluorooctane sulfonates (PFOS)) and PFCAs have been changing in higher trophic W DEQ-CFW 00000657 level wildlife and fish species, e.g. fish -eating birds and fish from the Laurentian Great Lakes and Arctic, and Arctic mammals such as seals, beluga and polar bears. Recent studies on PFAA trends, mainly of PFOS and PFCAs and detectable precursors, have shown differences in concentrations and patterns in wildlife and fish samples collected from urban versus more non -urbanized areas. For example, guillemot eggs collected in northwest Europe, skipjack tuna collected off -shore and in open -ocean in eastern Asia, and bottlenose dolphins collected in South Carolina all showed higher concentrations of PFCs in the samples that were collected closer to industrialized/urban areas. Very recently wildlife and fish studies have been reported on PFAA isomers of e.g. PFOS. This presentation will take a broad overview perspective and summarize on the current state of knowledge of bioaccumulative PFAAs in wildlife and fish worldwide, and with consideration of emerging PFAAs such as perfluorinated phosphonic acids (PFPAs). 05—PFAAs in Environmental and Biological Media Mark Strynar,' Andy Lindstrom,' Phillip Bost,2 Larry McMillan,3 Shoji Nakayama,4 and Amy Delinsky' 'U.S. Environmental Protection Agency, NERL, Research Triangle Park, NC; 2Student Services Contractor to the U.S. Environmental Protection Agency, NERL, Research Triangle Park, NC; 3National Caucus and Center on Black Aged Inc., Washington DC; 4U.S. Environmental Protection Agency, NRMRL, Cincinnati, OH Perfluorinated Alkyl Acids (PFAAs) are a globally distributed class of compounds that are found in humans, wildlife, and environmental samples. Occurrence measurements for PFAAs in environmental media is a first step in assessing baseline concentrations for the evaluation of transport and fate issues and to help characterize sources that may lead to human exposures. This data, coupled with human biomarker measurements and classical toxicology studies helps to inform the risk assessment process. To ensure adequate confidence in resulting data and study conclusions, it is necessary to establish robust methods with well defined performance characteristics. Our laboratory has developed a wide range of PFAA methods that have been used in a number of different studies. In general, PFAAs are extracted from environmental media (surface water, soil, house -dust) or biological media (fish, dosed rodent tissues, wildlife serum) using an organic solvent suitable for each specific application. Primary extractions are then generally followed by an optimized solid phase extraction (SPE) cleanup process prior to analysis by LC-MS/MS or LC-TOFMS. To obtain optimal assay performance, standard curves and QA/QC samples are prepared in matrix -matched blank material when available. Current methods being used for selected environmental and biological media will be discussed and results from recent studies will be presented. 06—Environmental -Fate Patterns for Perfluoroalkylates and their Precursors John W. Washington,' Peter J. Lasier,2 Hoon Yoo,31 J. Jackson Ellington,' and Thomas M. Jenkins41 'Ecosystems Research Division, National Exposure Research Laboratory, Office of Research and Development, Environmental Protection Agency, Athens, GA; 2U.S. Geological Survey, Patuxent Wildlife Research Center, Warnell School of Forestry and Natural Resources, The University of Georgia, Athens, GA; 3National Research Council (NRC); 4Senior Service America (SSA) Two sites with elevated concentrations of perfluoroalkylates (PFAs) and fluorotelomer alcohols (FTOHs) were studied: 1) agricultural fields near Decatur, AL on which sewage sludge had been applied; and 2) the Conasauga River system near Dalton, GA where treated sewage effluent is sprayed on land abutting the river. The sewage -treatment facilities at both sites received waste streams from industries that used fluorinated compounds. Decatur samples of surface soil, subsurface soil, and plants have been characterized for PFCs and FTOHs. Conasauga River water and sediments, collected from near Dalton, upstream and downstream, were characterized for PFAs. Additionally, oligochaetes (sediment -dwelling worms) exposed to the Conasauga sediments were analyzed for PFAs. For the Decatur study: 1) surface -soil perfluorocarboxylic acids (PFCAs) are statistically related to secondary FTOHs which are related to primary FTOHs suggesting sequential degradation is active in the soil; 2) PFAs are detected in subsurface soils and plants suggesting that leaching and plant uptake are active processes for PFAs in soils; 3) FTOHs are not detected in significant concentrations in subsurface soil or plants; 4) deep-soil/surface-soil PFCA ratios are greatest for short -chains and decrease with 19 DEQ-CFW 00000658 greater chain lengths suggesting higher mobility through the soil column for short chains; 5) disappearance half-lives for surface -soil PFCAs range from 1-5 y and increase with increasing chain length; and 6) disappearance half-lives for surface -soil FTOHs generally are about a year and do not trend with chain length. For the Dalton study: 1) C6 through C10 PFCAs and perfluorosulfonates (PFSAs) were detected in river water at Dalton and all sites down -river as far as Rome, GA; 2) C6 through C14 PFCAs and PFSAs were detected in river sediments at all sites albeit at higher levels from Dalton to Rome; 3) PFA levels that we detected in water and sediments appear to be lower than in samples collected in the past; and 4) oligochaetes grown in the PFA-rich sediments accumulated PFAs in their whole -body tissues. Taking Decatur and Dalton as model terrestrial and aquatic systems, respectively, patterns in PFA bioaccumulation factors for basal trophic levels, plant from soil for Decatur and oligochaete from detritus for Dalton, are compared. 07—Perfluorinated Chemicals in Consumer Articles —Monitoring the Market Trends Heidi Hubbard,' Zhishi Guo, Xiaoyu Liu,' Kenneth Krebs,' Nancy Roache,2 and Corey Mocka2 'U.S. EPA National Risk Management Research Laboratory, Research Triangle Park, NC; 2Arcadis, Research Triangle Park, NC Perfluorinated chemicals (PFCs), including perfluorooctanoic acid (PFOA) and other perfluoroalkyl acids (PFAAs), are of interest due to their associated negative health effects, including developmental toxicity in laboratory animals, and because of their widespread detection in humans, wildlife, and environmental media. Recent studies in Japan, Canada, and United States found elevated levels of perfluorooctanoic acid (PFOA), perfluorooctanoic sulfonate (PFOS), and other PFCs in house dust. Not only do these findings suggest the presence of indoor sources, but also suggest that inhalation of house dust could be one of the exposure pathways for these compounds. It is known that articles of commerce (AOCs) made from, or treated with, perfluoropolymers and perfluorotelomers may contain PFCs and are regarded as potential indoor PFC sources. The U.S. Environmental Protection Agency (EPA) launched the PFOA Stewardship Program in 2006 in which eight major companies in the fluorochemical industry committed voluntarily to reduce facility emissions and product content of 44 perfluorinated chemicals on a global basis by 95 percent no later than 2010 and to work toward eliminating emissions and product content of these chemicals by 2015. The ongoing market trend monitoring project is aimed to investigate the long-term trend for PFC content in AOCs and determine the origins of ADCs with high PFC content. It is anticipated the PFC content in AOCs will show an overall downward trend as the fluorochemical industry reformulates their PFC products. This study provides a means to independently check the degree of success of EPA's PFOA Stewardship Program. Sample collection and analyses are on -going for 12 product categories. Preliminary observations show a significant reduction of PFAA content in mill -treated stain -resistant carpeting. Similar reduction was observed for some, but not all, commercial carpet treatment products. Other product categories show mixed trends. An interim report will be published in late 2011. 08—PFAAs in Wastewater Treatment Plants and Sludge James Kelly' and Laura Solem2 'Minnesota Department of Health, St. Paul, MN; 2Minnesota Pollution Control Agency, Duluth, MN Perfluoroalkyl Acids (PFAAs) have been detected in the influent, effluent, and sludge of wastewater treatment plants (WWTPs) around the world, suggesting WWTPs are a significant source of PFAAs to the aquatic environment. PFAAs are discharged to WWTPs from residential, commercial and industrial sources where they are found in common consumer products and/or they are used in specific industrial applications ("point sources"). While PFAAs are not effectively treated or removed through typical WWTP practices, some degradation of PFAA precursors does occur, which can result in higher levels of PFAAs in the effluent and sludge compared to the influent. 20 DEQ-CFW 00000659 Since 2007, the Minnesota Pollution Control Agency (MPCA) has surveyed PFAA levels in WWTPs located across the state representing a variety of primary source loads and treatment technologies. This statewide assessment has identified several facilities as "outliers" indicative of a point source of PFAAs to the WWTP. A follow-up investigation in one case identified a chrome plating operation as a major source of perfluorooctane sulfonate (PFOS) to the Brainerd WWTP, described in a 2008 report by the Minnesota Department of Health (MDH). Broader implications of the release of PFAAs from WWTPs are only now coming into focus. Direct discharge of PFAAs into the aquatic environment can result in contamination of fish and other wildlife. Of perhaps greater concern is the direct use of contaminated WWTP sludge as a soil amendment on agricultural land or, in some cases, the composting of sludge for subsequent sale to individuals and businesses for use in home and commercial gardens. Several studies have shown that some PFAAs can be taken up by plants in a concentration dependent manner, introducing another pathway by which people and wildlife may be exposed to PFAAs. To address environmental and public health risks associated with PFOS in the aquatic environment, the MPCA has derived a surface water quality standard of 7 ng/L for Pool 2 of the Mississippi River, and the MDH has developed health -based exposure advice for fish consumption of >40 ng/g (1 meal/week) and >200 ng/g (1 meal/month). Fish from the Mississippi River from northern Minnesota to near the Iowa border have been tested for PFAAs; MDH has issued consumption advice ranging from unrestricted to 1 meal per month based on PFOS concentrations. Limited testing has also been done in the Minnesota and St. Croix rivers. To date, MPCA and MDH have tested fish from 127 lakes in Minnesota for PFAAs. MDH has issued fish consumption advisories for 34 Minnesota lakes based on PFOS; the vast majority of these lakes are in the Twin Cities metro area. The specific source(s) of PFOS at many of these lakes remains unknown. While much has been accomplished in Minnesota, much work remains to be done. Future activities will focus on continued monitoring of PFAAs at WWTPs, possible follow-up investigations to identify point sources to WWTPs, a study of PFAA exposures through other pathways such as plant uptake from impacted soil and water, and working towards a better understanding of the distribution of PFCs in surface waters, fish and wildlife. 09—PFAA Exposure to Farm Cattle Kerry L. Dearfield USDA/FSIS/OPHS, Washington, DC Perfluoro-compounds (PFCs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are used in the manufacture of plastics, electronics, non-stick coatings and stain repellents. PFOS and PFOA are environmentally stable and have the potential to be exposed to wildlife and livestock. Toxicity studies indicate potential adverse effects associated with exposure to PFCs and include developmental effects, liver hypertrophy, elevated hormone levels and lipoprotein abnormalities. In the southeastern USA, bio-sludge generated from waste treatment found to contain PFOS and PFOA was applied to agricultural fields. Cattle are likely to be exposed to these compounds via vegetation which grew on bio-sludge treated soils as well as waters treated at waste treatment plants. The US Department of Agriculture's Food Safety and Inspection Service (USDA/FSIS) is concerned about possible adverse public health effects associated with human dietary PFOS and PFOA exposure from beef derived from these cattle. Data were initially limited to site -specific concentrations of PFOS and PFOA in soil and water. Using this information, USDA/FSIS developed a quantitative model that considers environmental fate of these compounds, pharmacokinetics and distribution of these chemicals in food animal tissues, and dietary patterns of U.S. consumers. This model provides estimates of the potential exposure to PFOA and PFOS, and subsequent public health risk to consumers of these cattle. This information is being used to inform food safety risk management activities at USDA/FSIS. 21 DEQ-CFW 00000660 010—PFAAs in Food and Migration from Food Packaging Timothy H. Begley Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Regulatory Science, College Park, MD Perfluorochemicals because of their stability and chemical resistance are widely used in the manufacturing and processing of a vast array of consumer goods, including electrical wiring, medical devices, clothing, household, and automotive products. Furthermore, relatively small quantities of perfluorochemicals are also used in the manufacturing of food contact substances (FCS) which represent potential sources of oral exposure to these chemicals. The most consumer recognizable food contact materials containing perfluorochemicals are non-stick cookware coatings made of polytetrafluoroethylene (PTFE). Additionally, perfluorochemicals are used in paper coatings for oil and moisture resistance in the fast food industry. Recent epidemiology studies have demonstrated the presence of two particular perfluorochemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human serum at very low part per billion (ppb) levels. These perfluorochemicals are biopersistent and are the subject of numerous studies investigating the many possible sources of human exposure. Because of this potential for biopersistence, FDA is evaluating the migration characteristics of perfluorochemicals from food contact materials and determining their presence in some foods. In this presentation, the types of perfluorochemicals used in food contact materials will be illustrated, along with methods for their determination. Additionally, research will be presented on the amounts of PFOA and fluorochemicals in food contact materials and the migration of these chemicals into foods or food simulating liquids. Results from migration tests show that fluorochemicals from food packaging can transfer to food at ppb to low ppm levels. Additionally results will be presented on the recent analysis of raw and retail milk for perfluorochemicals. 011—A Brief Overview of PFAA Epidemiology Geary W. Olsen Medical Department, 3M Company, St. Paul, MN The number of epidemiology literature papers published on a few perfluorinated alkyl acids (PFAA) has increased considerably in the last five years, although the number of papers is still modest in absolute terms. The epidemiology research has focused on populations with measured serum or plasma concentrations of the dissociated anions perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) over a wide range of concentrations. These populations include: 1) occupationally exposed workers from past and present manufacturers of PFOA and PFOS; 2) a mid -Ohio River Valley community exposed to PFOA through contaminated drinking water; and 3) general populations whether they are identified as statistically representative samples (e.g., NHANES), cohorts that were originally established for other research reasons (e.g., Danish Diet and Health Study), or self -described study populations. In addition, numerous biomonitoring assessments have also been published of general populations in North America, Europe, and Asia, although most lack any epidemiologic component. The majority of the epidemiologic studies have employed cross -sectional study designs but a few longitudinal assessments of clinical and self -reported outcomes, several occupational cohort mortality studies, and one general population case -cohort study are found in the literature. Although a wide breadth of health endpoints have been evaluated with PFAAs, this body of literature is deepest in a few areas that have been the subject of targeted research hypotheses that were based on toxicological evidence from laboratory animal studies. Rather than surveying the breadth of the literature, the co-chairs of the PFAA Days III epidemiology session thought a more focused presentation and discussion should occur with these in-depth data. This would offer meeting registrants the greatest opportunity for enhanced understanding of this information and its methodological underpinnings and uncertainties. To meet this objective, three research areas were selected for presentation and discussion. The first series of presentations involve an overview of the C8 Science Panel, its cross -sectional investigations, and the ongoing reconstruction of exposure assessment activities in the mid -Ohio River Valley with prediction of PFOA serum levels. The second set of presentations will review the epidemiologic evidence related to serum lipids (and associated conditions DEQ-CFW 00000661 including heart disease and type II diabetes) with exposure to PFOA and PFOS from both the non - occupational and occupational perspectives. Positive associations between serum concentrations of non - high density lipoprotein cholesterol and serum concentrations of PFOA and PFOS have been reported. However, the magnitude of these associations cannot be extrapolated across substantively different PFOA and PFOS exposure levels, and are contrary to the toxicological findings that have observed either a decrease or no change in serum lipids and serum cholesterol and/or triglycerides in laboratory animals, including cynomolgus monkeys. The final set of presentations will review and offer insights into the epidemiology associations that have been reported from community and general population studies regarding human fetal development endpoints (e.g., birth weight, duration of gestation) with measured maternal and/or cord blood PFOA and PFOS concentrations. Physiologic considerations that occur during pregnancy will be discussed in light of some of the associations reported between PFOA and/or PFOS concentrations with lower birth weight, that, nevertheless, remain well within the normal birth weight range. 012—The C8 Science Panel Program and Findings from Cross Sectional Analyses of C8 and Clinical Markers in the Mid -Ohio Valley Population Tony Fletcher Department of Social and Environmental Health Research (formerly the Public and Environmental Health Research Unit), London School of Hygiene and Tropical Medicine, London, UK In the mid -Ohio valley in the USA, drinking water in six water districts has been contaminated for approximately 50 years with PFOA ((perfluorooctanoic acid, also known as C8), which was released by a nearby Teflon manufacturing facility. The exposure of a community to this compound led to litigation against the polluting company. Part of the settlement was the establishment of the4 3 members of the C8 Science Panel who are conducting a comprehensive epidemiological program assessing potential health effects in the exposed population, to provide essential dato to assist the Panel in its primary role: to assess if there are any "probable links" between PFOA exposure and disease. This presentation will introduce the C8 Science Panel's role and research program, and present some findings. The Panel's work is described in detail on our website: (www.c8sciencepanel.org). Different components of the research program are led by different science panel members and their research collaborators, and several complementary talks at this meeting will present our findings. In this presentation I shall present some results from our studies of clinical markers of immune and endocrine function. Immunoglobulins (IgA, IgE, IgG, IgM) , antinuclear antibodies (ANA) and C-reactive protein inflammatory marker (CRP), were all measured in a baseline survey of 69,030 community residents conducted in 2005/6. We have investigated their relationship to serum levels of both PFOA and PFOS measured at the same time. Significant associations do not necessarily imply causal relationships, especially in large cross sectional studies with small magnitudes of effect, so associations that show some consistency across gender, compound and high vs. low exposure area, provide more persuasive evidence. The associations between PFOA or PFOS and IgA and CRP yielded the most significant and consistent findings. We are currently collecting blood in a sample of 800 adults who participated in the 2005/6 survey and repeating the panel of clinical markers which will enable us to assess any trends in relation to the falling trend of PFOA in the same population. In addition we have done a comparison of assays on free thyroxin (fT4). Some experimental work in rodent studies of PFOS on thyroid function suggested that the more common measure of total or free T4 the "analogue method", can be underestimated in the presence of PFOS, but the equilibrium dialysis method was immune to this bias. Whether this was the case in human serum, at much lower concentrations and also for PFOA was not known. We have measured fT4 by both methods in a sample of 50 participants and we have found no evidence of a PFOA or PFOS dose -related difference between the two methods. 23 DEQ-CFW 00000662 014—PFAAs and C8 Study with Type II Diabetes, Uric Acid, and Lipids Kyle Steenland Emory University, Atlanta, GA Data will be presented from a 2005-2006 cross -sectional study of 69,000 residents of Ohio and W. Virginia, who were exposed to drinking water contaminated with PFOA. The mean and median PFOA serum levels for these residents was 83 ng/ml and 28 ng/ml, respectively, compared to about 4-5 ng/ml serum levels for the general US population. PFOS levels in this population were similar to the US population; PFOS and PFOA were positively correlated (Spearman correlation coefficient 0.32). Outcomes of interest included cholesterol, uric acid, and self -reported diabetes; there is some prior evidence in the literature associating these outcomes with PFOA. In our population, total cholesterol was positively associated with increasing levels of PFOA as well as PFOS. The odds ratios for high cholesterol (>240 mg/dL), by increasing quartile of PFOA, were 1.00, 1.21 (95% confidence interval (Cl): 1.12, 1.31), 1.33 (95% Cl: 1.23, 1.43), and 1.40 (95% C1:1.29, 1.51) and were similar for PFOS quartiles. LDL and triglycerides were also each positively associated with PFOA, while HDL was not. For uric acid, again associations were found with both PFOA and PFOS. Hyperuricemia risk increased modestly with increasing PFOA; the odds ratios by quintile of PFOA were 1.00, 1.33 [95% confidence interval (CI), 1.24- 1.43], 1.35 (95% Cl, 1.26-1.45), 1.47 (95% Cl, 1.37-1.58), and 1.47 (95% Cl, 1.37-1.58), with similar but slightly weaker trend for PFOS quartiles. Neither self -reported Type II diabetes, medically validated Type II diabetes, nor fasting glucose showed any trend with PFOA measured in 2005-2006. Restriction of the population to long term residents, for whom serum PFOA in 2005 would be expected to reflect long term exposure, did not change these results for diabetes. All results from this population should be interpreted with caution due to the cross -sectional nature of these data, which generally precludes knowing whether exposure preceded outcome. 015—PFOA and Heart Disease: Epidemiologic Studies of Occupationally Exposed Populations J. Morel Symons DuPont Epidemiology Program, Newark, DE Perfluorooctanoic acid (PFOA) is a biopersistent compound of public health interest due to its detection in environmental media and blood samples from humans and wild animals. Clinical and toxicologic effects evaluated for exposure to PFOA have been described by a wide variety of research studies. The focus of this presentation will be on the methods and results of epidemiologic studies of occupational exposure to PFOA. Biomonitoring for PFOA in whole blood and serum samples has been conducted for several decades. Published results from observational cohort studies include more than 12,000 workers located primarily in the United States. Cross -sectional and longitudinal examinations have assessed PFOA levels and potential associations with lipids, metabolic products, and liver enzymes for various groups of these workers. Follow-up studies have evaluated disease -specific morbidity and mortality outcomes among site - based cohorts with varying degrees of occupational exposure. Workers have higher potential for exposure relative to other identified populations, primarily through the production and use of the ammonium salt of PFOA. Median estimates of serum PFOA for employee groups range from 0.1 to 5 parts -per -million (ppm). Most occupationally exposed persons have serum PFOA levels that are several orders of magnitude higher than the median estimates for general populations and for residents of two locales primarily exposed to contaminated water supplies. Results from two of three occupational cohorts have indicated positive relationships between serum PFOA and total cholesterol (notably low -density lipoproteins) and uric acid. Other clinical chemistry results show inconsistent associations among all exposed workers. Increased lipids are an established risk factor for cardiovascular disease. The relationship between increased uric acid levels and cardiovascular disease is less certain with regard to its status as an independent risk factor. In the case of total cholesterol, the magnitude of estimated change among non -occupationally exposed persons is relatively higher at lower exposure levels. This may indicate a non -linear exposure -response 24 DEQ-CFW 00000663 relationship. Reported absolute changes in total cholesterol for both occupational and non -occupational groups are approximately similar regardless of the magnitude of change in PFOA serum levels. Moreover, the observation of increased total cholesterol in humans contrasts with toxicologic studies which report hypolipidemia in rodents and no response among nonhuman primates. Epidemiologic studies of workers published to date have reported few positive associations with morbidity and mortality from cardiovascular and related diseases. Follow-up studies for two occupational cohorts have shown no association with ischemic heart disease (IHD) mortality and inconsistent associations with cerebrovascular disease mortality based on general population reference rates. Observed diabetes mortality was increased among 3M workers classified as having probable PFOA exposure relative to expected deaths based on Minnesota population rates. The study reported no diabetes deaths among more highly exposed workers classified as having definite PFOA exposure. A study of DuPont workers reported decreased diabetes mortality compared to general United States and West Virginia population rates and an increase in diabetes mortality relative to rates for regional DuPont employees. Results from mortality comparisons should be interpreted with caution due to limitations in ascertainment of diabetes as a cause of death. A separate analysis of incident diabetes among persons without occupational exposure found significant decreases of 20 to 40% in diabetes risk among persons with serum PFOA levels above 0.008 ppm. A study of DuPont fluoropolymer production workers showed no excess risk for myocardial infarction incidence and coronary heart disease mortality based on rates for national DuPont employees. A later study expanded the size and follow-up period for the cohort. Standardized mortality ratios were significantly decreased for IHD mortality compared to general United States and West Virginia population rates with a slight positive association relative to regional DuPont employee rates. A subsequent analysis evaluated IHD mortality risk for five cumulative exposure periods at multiple lagged intervals. The results of this study indicated no statistically significant association between IHD mortality and occupational exposure to PFOA. The practice of epidemiology is of continuing importance for examining human health and PFOA exposure. Possible confounding related to heterogeneity within and between studied populations may influence the interpretation of analyses of PFOA and clinical chemistries. Differential distributions of risk factors such as diabetes prevalence could affect measured serum PFOA, lipids, and uric acid levels. The indication of non -linear exposure -response relationships characterized by steeper regression slopes at lower PFOA serum levels should also be investigated. In conclusion, based on current epidemiologic results from occupationally exposed populations, PFOA does not appear to be associated with cardiovascular disease. A study of incident heart disease is currently being conducted to further assess this relationship. 016—Epidemiology of Reproductive and Developmental Health Effects of PFAAs Cheryl R. Stein Mount Sinai School of Medicine in New York, NY Experimental studies have suggested perfluoroalkyl acids (PFAAs) may be associated with reproductive toxicity, and there is some epidemiologic support for a small effect on infant size at birth. We reviewed the basis for a concern with reproductive toxicity as well as the epidemiological literature on the reproductive and developmental health effects of PFAAs. Additionally, using data from the C8 Health Project, we examined the association of serum perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with self -reported pregnancy outcome in Mid -Ohio Valley residents (2000-2006) highly exposed to PFOA. Data on 1,845 pregnancies within the 5 years preceding exposure measurement were analyzed for PFOA, and data on 5,262 pregnancies were analyzed for PFOS. Generalized estimating equations were used to calculate adjusted odds ratios and 95% confidence intervals. Neither PFOA nor PFOS showed any association with miscarriage or preterm birth. Preeclampsia was weakly associated with PFOA (adjusted odds ratio 1.3, 95% confidence interval: 0.9, 1.9) and PFOS (adjusted odds ratio 1.3, 95% confidence interval: 1.1, 1.7) exposures above the median. PFOA was not associated with an increase in low birthweight, but PFOS showed an increased risk above the median 25 DEQ-CFW 00000664 (adjusted odds ratio 1.5, 95% confidence interval: 1.1, 1.9) and a dose -response gradient. Birth defects were weakly associated with PFOA exposures above the 90th percentile (adjusted odds ratio 1.7, 95% confidence interval: 0.8, 3.6). This study identified modest associations of PFOA with preeclampsia and birth defects, and of PFOS with preeclampsia and low birthweight, but associations were small, limited in precision, and based solely on self -reported health outcomes. 017—PFAAS and Pregnancy Outcomes in General Population Studies, Methodological Considerations, Physiology of Pregnancy Considerations, and Future Research Matthew P. Longnecker Epidemiology Branch, National Institute of Environmental Health Sciences NIH, DHHS, Research Triangle Park, NC In general population studies, the plasma or serum concentration of certain perfluorinated alkyl acids (PFAA) in pregnant women or cord blood has been associated with lower birthweight, albeit inconsistently. Furthermore, the concentration of plasma PFAA ([PFAA]) in pregnant women has been associated with an increased time -to -pregnancy in one general population study. In this presentation, the author will consider whether physiologic aspects of pregnancy and lactation might account for the observed associations, in the absence of a causal effect of PFAA on birthweight or fecundability. A reduction in maternal plasma PFAA level during pregnancy and during lactation has been documented. Several of the normal changes and processes that take place during pregnancy and lactation affect the concentration of maternal plasma PFAAs, and the correlated levels in cord blood. The proportion of the overall change in PFAA levels during pregnancy due to specific aspects of physiology is unknown. However, certain predictions regarding magnitude and direction of effect are possible. Maternal plasma volume increases during pregnancy, and this increase is proportionally greater than the overall weight gain during pregnancy. If the ratio of concentration of PFAAs in the intravascular and extravascular compartments remains constant during pregnancy, the increase in plasma volume would cause a slight decrease in plasma PFAA level. The plasma volume expansion during pregnancy is proportional to the weight of the infant delivered. Using realistic assumptions, this relationship is of a magnitude sufficient to cause a 1-2% difference in plasma PFAA levels between infants born small -for - gestational age (SGA) and those born normal weight for gestational age (higher [PFAA] for SGA). Furthermore, the increased plasma volume would increase renal perfusion and the glomerular filtration rate. Because some PFAA is eliminated via urine, the increased filtration could result in greater loss of PFAA, giving a second reason for lower [PFAA] in pregnancies ending with normal weight infants compared with SGA infants. A large proportion of PFAA in plasma is bound to albumin, and the concentration of albumin in plasma decreases during pregnancy. This decrease in [albumin], however, appears to be unrelated to birthweight, and thus while it may contribute to a decrease in plasma [PFAA], the phenomenon probably does not account for an association of [PFAA] with birthweight. During pregnancy, some of the mother's body burden of PFAA is transferred to the fetus. After pregnancy, additional PFAA is transferred to the infant, via lactation. For a woman breastfeeding for 6 months, the overall effect of pregnancy and lactation on her plasma [PFAA] would be a substantial decrease. Given the long half life in plasma of the major PFAAs, after lactation ends, a slow rise in [PFAA], towards the pre -pregnancy level, would be expected. During that period of rising [PFAA], the woman may attempt another pregnancy. The longer it takes her to become pregnant, the longer she has for her [PFAA] to increase. On this basis, measurement of plasma [PFAA] during pregnancy in parous women would be expected to show higher levels among those who took longer to get pregnant. Preliminary data on plasma PFAA levels during pregnancy in relation to birthweight of the offspring, as well as time -to -pregnancy from the Norwegian Mother and Child Cohort Study (MoBa) will be presented. The results will be compared with findings from other studies, and all will be discussed in the context of associations predicted based on the phenomenon described above. A poster presented by Dr. Kristi Whitworth et al. at the conference will present a more detailed analysis on the time -to -pregnancy association. 26 DEQ-CFW 00000665 With respect to implications of the phenomena described above, the following are offered. For prospective studies of PFAAs and birthweight, and for retrospective studies of pregnancy PFAAs and fecundability, studies based on measurements of blood levels during pregnancy may show inverse associations because of pharmacokinetics, in the absence of causality. If PFAA were measured before pregnancy and related to birthweight, the types of bias discussed would not be an issue. Similarly, if PFAA were measured before attempting pregnancy and related to time -to -pregnancy, the bias discussed would not be an issue. Such prepregnancy studies, however, while possible, are challenging and few have been done to date. Retrospective time -to -pregnancy studies may be informative if limited to nulliparous women. Reference: Olsen GW, Butenhoff JL, Zobel LR. Perfluoroalkyl chemicals and human fetal development: an epidemiologic review with clinical and toxicological perspectives. Reprod Toxicol. 2009;27(3-4):212-30 018—An Overview of PFAA Pharmacokinetics Harvey Clewell, Anne Loccisano, and Melvin Andersen The Hamner Institutes for Health Sciences, Research Triangle Park, NC Determining the relationship between exposure to PFAAs and measured concentrations in plasma has been hindered by the lack of pharmacokinetic data in humans. For convenience, the pharmacokinetics of PFAAs have been described with one -compartment, first -order models; however, the observed kinetics in animals is clearly more complicated. During studies with daily oral dosing and extended post -exposure observation periods, cynomolgus monkeys have a rapid approach to steady-state plasma concentrations together with a very much slower terminal half-life. Moreover, changes in apparent elimination rates with increasing dose suggest that capacity -limited, saturable processes must be involved in the kinetic behavior of these compounds. We have developed PBPK models for PFOA and PFOS in the monkey and rat, and have performed an initial extrapolation of these models to the human. This presentation will describe the alternative approaches for modeling PFAAs (simple and biologically motivated) and discuss their relative strengths and weaknesses for estimating the exposures likely to be associated with blood levels of PFOA measured in a population, and for comparing these exposures with health benchmarks from animal studies. 019—Organic Anion Transporters and PFAA Tissue Distribution Yi M. Weaver,' David J. Ehresman,2 Shu-Ching Chang,2 John L. Butenhoff,2 and Bruno Hagenbuch' 'Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS; 2Medical Department, 3M Center, St. Paul, MN Renal elimination and liver accumulation of perfluoroalkyl acids (PFAAs) is dependent on their chain length, isomeric structure, species, and sometimes gender within a species. In general, shorter chain length PFAAs are eliminated more efficiently by the kidneys whereas the longer chain length PFAAs preferentially accumulate in the liver. It was hypothesized that the underlying mechanism for the different handling of PFAAs could be explained by transport proteins expressed in a tissue and gender specific way. It has been shown that the more hydrophilic organic anions with lower molecular weights are mainly transported by members of the organic anion transporters (OAT; SLC22A family), transporters that are preferentially expressed in the kidneys. The more hydrophobic organic anions with larger molecular weights are preferentially transported by members of the organic anion transporting polypeptides (OATP; SLCO family) that are mainly expressed in hepatocytes. Inhibition experiments have demonstrated that transport by the rat renal Oat1 and Oat3 was maximally inhibited by the shorter perfluorohexanoate (C6), perfluoroheptanoate (C7) and perfluorooctanoate (C8), while transport mediated by the liver expressed Oatp1al was maximally inhibited by perfluorononanoate (C9), perfluorodecanoate (C10) and perfluoroundecanoate (C11). Direct uptake measurements revealed that C7 to C8 were transported with higher affinities by Oat1 and Oat3 while C9 and C10 were transported with higher affinities by Oatp1 al. Similar results were found for some of the human OATPs. The liver specific OATP1 B1 and OATP1 B3 transported C8 to C10 better than C7, suggesting that liver accumulation of the longer chain PFAAs may indeed be due to the fact that these compounds are better substrates for OATPs as compared to OATs. In conclusion, the available experimental data support the hypothesis that the observed PFAA distribution DEQ-CFW 00000666 to the kidneys and the liver is due to the preferential expression of kidney and/or liver specific transporters. 020—Translating Toxicological Information on Perfluoroalkyls for Human Risk Assessment John L. Butenhoff 3M Company, Medical Department, St. Paul, MN Since the confirmation of the widespread presence of perfluoroalkyls in biological samples from non - occupationally exposed human populations and wildlife in the late 1990s, significant advancements have been made in our understanding of the biological interactions of many of these related compounds. While perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) have been the anchor points for investigation, the range of perfluoroalkyls and polyfluoroalkyls that have come under study has continued to increase. Moreover, the number and global distribution of investigators has increased correspondingly, resulting in rapid growth of the scientific literature related to the toxicological and human health implications of exposure to per- and poly- fluoroalkyls. Lest movement over this sea of data toward a clear understanding be influenced overly by the winds, tides, and storms of data, it becomes prudent to take a bearing from time to time on our position and chart our course forward. In doing so, it is important to attempt to take a broad view of all the information available in order to synthesize the whole from the pieces. For example, it is clear today that differences observed in type of responses and dose -response patterns between the various compounds studied and, for a compound under study, between species, can be better understood by studying transport processes and biological interactions at a molecular level. It is also important to establish clear lines of communication between the various specialty fields, and in particular, between those of Epidemiology and Toxicology. Although the number of studies being reported continues to increase, areas of major focus in Toxicology have resolved into the following: oncogenesis; hepatotoxicity; metabolic function; immune function; reproduction; development; hormonal changes; neurological effects. The status of research with perfluoroalkyls in each of these areas is briefly discussed. With respect to toxicological studies providing insight on cancer risk, a combination of genotuxicity studies, chronic bioassays, and mechanistic studies is presently available. Perfluoroalkyls do not possess the chemical/physical properties typically associated with directly genotoxic agents. At the present time, we have four Sprague Dawley rat dietary toxicological studies available that inform us about the oncogenic potential of perfluoroalkyls: two for PFOA (as ammonium salt); one for PFOS; one for N-ethyl- N-(2-ethoxy)-perfluorooctanesulfonate (N-EtFOSE, which generates PFOS as a metabolite). None of these studies has shown a statistically significant increase in any type of malignant tumor. An increase in benign liver tumors was observed in one PFOA study and with PFOS and N-EtFOSE. Based on several mechanistic studies, the origin of liver tumors from exposure of rats to PFOA and PFOS is currently believed to be the result of a combined activation of the xenosensor nuclear receptors, PPARa, CAR, and PXR. Recent advances in our understanding of differences between rodents and humans with respect to the proliferative response to activation of these receptors allows valuable perspective for human risk assessment in that human PPARa and CAR/PXR support the hepatic hypertrophic response but not the hepatic hyperplastic response, which is necessary for tumor formation. Pancreatic acinar cell tumors were also increased in one PFOA study, and testicular Leydig cell tumors were increased in both PFOA studies. Insights have been gained as to the etiology of these two additional tumor types. It has been reported in secondary sources that female rat mammary tumors were increased by PFOA; however, this was not the conclusion of the study authors, and the lack of an increase in mammary tumors has been confirmed after a complete audit of the study followed by a pathology working group review. N-EtFOSE increased thyroid follicular cell tumors in male rats, as did PFOS, but PFOS did so only in males for whom dosing was suspended after one year and not for males dosed for two years. Treatment of rodents with several of the perfluoroalkyls has resulted in hepatomegaly and hepatocellular hypertrophy, often without evidence of overt hepatotoxicity. These effects have also been observed in 19 DEQ-CFW 00000667 monkeys. The hepatic hypertrophic response is now believed to be due, in large part, to activation of PPARa and CAR/PXR. PFOA has also been found to increase proliferation of mitochondria. Activation of xenosensor nuclear receptors PPARa and CAR/PXR as well as potential mitochondria) interactions have potential metabolic implications. For those perfluoroalkyls which have been studied in toxicological systems, decreased serum/plasma cholesterol and and/or triglycerides are frequently observed clinical chemistry findings in toxicological studies. Changes in the lipid content of hepatocytes have also been noted. The roles of PPARa and CAR/PXR in mediating these changes have become clearer in recent years. For example, the hypolipidemic effects of perfluorohexanesulfonate (PFHxS) and PFOS can be ascribed to PPARa and PXR mediated changes in the formation and clearance of lipoproteins. A number of rodent immunotoxicology studies have been published on PFOA and PFOS. In general, these studies have provided evidence of effects on inflammatory responses, production of proteins involved in immune responses, lymphoid organ weights, and antibody synthesis. Reported findings have been somewhat inconsistent, and have varied with dose, strain, and dosing methodology. Although observed responses have been shown to be driven, in part, by PPARa, the need to study also the role of PPARa-independent processes and other factors that may affect the nature of observed responses has become clear. Several perfluoroalkyls have been studied for their potential to disturb reproduction in rats. Overt effects on reproductive function in male and female rats generally have not been observed. Increased early full - liter resorption is one effect noted in female rodents dosed with PFOA during gestation. This may be more the result of an effect on the maintenance of pregnancy in the rodent than an embryotoxic effect. Because there are significant differences between humans and rodents in the maintenance of pregnancy, it is important to develop a better understanding of this observation. Since the first observation of perinatal mortality in a multi -generation study of PFOS in rats, there have been numerous developmental studies undertaken to increase understanding of the potential developmental toxicity of perfluoroalkyls. The prenatal developmental effects of these compounds largely are unremarkable. Postnatal mortality, developmental delays, and stunting of development of mammary tissue have been a major focus of research. A principal role for PPARa in mediating the developmental effects of PFOA in mice has been discovered. How this finding translates to potential human relevance requires additional insight and discussion. In the case of PFOS, post -natal developmental effects appear to be either not mediated by PPARa or at least largely independent of PPARa. Potential interference with the functional properties of pulmonary surfactant at birth has been and continues to be a leading hypothesis for the basis of PFOS postnatal developmental effects. Hormonal investigations have focused primarily on the etiology of PFOS-induced hypothyroxinemia in toxicology studies and investigation of changes in sex hormones for PFOS and PFOA. PFOS-induced hypothyroxinemia in rats appears to be the result of increased displacement from serum carrier proteins and increased uptake and elimination by the liver and kidney. Although PFOA has been shown to increase serum estradiol in male rats, PFOS and PFOA decreased serum estradiol in monkeys at relatively high doses. The increase in estradiol in male rats may be the result of a PPARa-mediated induction of aromatase. Most of the responses observed with perfluoroalkyls, either as early responses occurring during the course of repeat dosing or as responses occurring at lower doses, do not suggest the nervous system as a primary site of action. It is perhaps for this reason that fewer neurotoxicological investigations have been undertaken. Even after lethal or sub -lethal doses, there has not been compelling evidence of neurotoxicological damage at doses relevant to risk assessment. In summary, in navigating the vast sea of data on the biological interactions of perfluoroalkyls, it appears we should set our sights on expanding our understanding of the molecular biological, metabolic, and physiological bases of responses observed in laboratory toxicology studies. Even more important, however, is incorporating an understanding of epidemiological investigations as we try to gain perspective on the toxicological data. Translating understanding from toxicological systems into a human context will improve our collective ability to understand potential human -health risk from environmental levels of exposures to these agents. DEQ-CFW 00000668 021—PFAA Ecotoxicology John L. Newsted Entrix, Okemos, MI; Michigan State University, East Lansing, MI Perfluorinated compounds (PFCs) have been manufactured for over 50 yr and, due to their unique properties of repelling both water and oil, have been used in numerous products that have resulted in their release into the environment. Since 2001 when Giesy and Kannan reported on the global distribution and bioaccumulation of several PFCs in fish, birds and mammalian wildlife, significant effort has been put measurement of these compounds to better characterize their distribution in biotic and abiotic matrices. In addition, development of improved analytical methods has allowed researchers to identify additional perfluorinated compounds and classes in the environment such as the fluorotelomer alcohols and perfluorophosphate surfactants. While analytical methodology has allowed the detection of these compounds at ever decreasing levels, the ecotoxicological significance of these compounds remains largely unknown. Of the perfluorinated chemicals tested to date, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have been the most extensively studied in ecologically relevant species. As a result, this presentation will focus principally on PFOS with several objectives in mind: (1) to provide an up-to-date overview of currently available toxicological data for aquatic and terrestrial species, (2) to put these data into context relative to establishing toxicity reference values and water quality criteria for aquatic species and wildlife, (3) to identify data gaps that will need to be addressed reduce the uncertainties in the hazard assessments of this compounds, and (4) draw comparisons between what is know about ecotoxicological effects of PFOS to other PFCs such as PFOA and fluorotelomer alcohols to provide some insight Into potential hazard to ecological systems. 022—A Brief Overview of PFAA Modes of Action Chris Corton Integrated Systems Toxicology Division, National Health and Environmental Effects Research Lab, U.S. EPA, Research Triangle Park, NC Several putative modes of action have been suggested to account for the adverse effects induced by perfluorinated alkyl acids (PFAAs). These will be briefly summarized. In particular, in mouse and rat Ilver PFAAs including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) elicit transcriptional and phenotypic effects similar to peroxisome proliferator chemicals (PPC) that work through the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa). Recent studies indicate that along with PPARa, other nuclear receptors are required for transcriptional changes in the liver after PFAA exposure including the constitutive activated receptor (CAR) and other PPAR family members. This session will focus on examining the role of these and other nuclear receptors in toxicities in the liver or extra -hepatic tissues including developmental toxicity, immunotoxicity, and metabolic changes that may be linked to metabolic syndrome. 023—PPAR Involvement in PFAA Developmental Toxicity Barbara D. Abbott Developmental Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC. Perfluoroalkyl acids (PFAAs) are found in the environment and in serum of wildlife and humans. Perfluorooctanoic acid. (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) are developmentally toxic in rodents. The effects of in utero exposure include increased neonatal death, developmental delay, and deficits in postnatal growth. Members of the PFAA family of compounds were shown to activate peroxisome proliferator-activated receptor -alpha (PPAR(x) in a transfected Cos-1 cell model. PPARa, PPAR(3/5 and PPARV, are expressed in human and rodent embryos with tissue and developmental stage -specific expression patterns. PPARs have significant physiological roles, regulating energy homeostasis, adipogenesis, lipid metabolism, inflammatory responses, and hematopoiesis. Studies in PPARa knockout (KO) mice revealed a role for PPARa in the induction of developmental toxicity by PFOA and PFNA, but not PFOS. The induction of postnatal lethality by PFOS may be related 30 DEQ-CFW 00000669 to effects on lung function. In fetal lung and liver, PFOA and PFOS altered gene expression and in fetal liver both compounds produced profiles typical of PPARa activation. Activation of some genes in liver persisted to PND63. Fetal and neonatal heart also showed altered gene expression after exposure to PFOA. Effects in heart differed from liver and were found at least to PND28. Although it is not clear exactly how changes in gene expression are related to the effects on neonatal survival and growth, perturbation of PPARa-regulated lipid and glucose homeostasis potentially impact energy availability and utilization. The absence of developmental toxicity in the PPARa KO mouse and alterations in gene expression typical of PPARa activation in the wild type mouse, support a role for PPARa in mediating the developmental toxicity of PFOA and PFNA. The primary cause of PFOS-induced developmental toxicity is PPARa-independent and may be an effect on lung function. However, PFOS altered gene expression in a manner similar to PFOA and if effects on PPARa-regulated genes are responsible for developmental toxicity, then it is expected that PFOS would still produce developmental toxicity even in absence of an effect on lung function. This abstract does not necessarily reflect US EPA policy. 024—Nuclear Receptor Involvement in PPAR-Induced Metabolic Changes Mitch B. Rosen Integrated Systems Biology, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC It has been proposed that certain xenobiotics commonly identified in biomonitoring studies may play a role in the incidence of obesity and metabolic syndrome in the United States and other countries. The list of potential "environmental obesogens" includes endocrine disrupting compounds such as Diethylstilbesterol and Bisphenol A, as well as chemicals that present a variety of toxicities in mammals such as the organotins. Interestingly, perfluoroalkyl acids (PFAAs) have also been mentioned as possible environmental obesogens because of their ability to alter energy homeostasis. While it may not be clear how compounds that function as peroxisome proliferator activated receptor alpha (PPARa) ligands could induce obesity, the biological activity of PFAAs is not limited to activation of PPARa. Many of these compounds also activate the constitutive androstane receptor (CAR) and it is now recognized that CAR influences not only xenobiotic metabolism but also certain aspects of energy metabolism as well. Chronic exposure to PPARa agonists also has the potential to alter energy metabolism in ways that are only first beginning to be understood. For example, chemical or metabolic challenge during gestation could result in PPARa-dependent epigenetic modifications which result in persistent alterations in phenotype. This talk will consider the potential effects of chronic PFAA exposure on nuclear receptor regulated energy metabolism. (This abstract does not necessarily reflect EPA policy.) 025—PPAR Involvement in PFAA Immunotoxicity JC DeWitt,' MM Peden -Adams, 2 DE Keil, 2 and SE Anderson 'Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC; 2Clinical Laboratory Sciences, University of Nevada, Las Vegas, NV; 3Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV When immune endpoints are evaluated in experimental animals exposed to PFAAs, alterations in antibody synthesis, inflammatory responses, cytokine production, lymphocyte cellularity, and lymphoid organ weights are reported. These alterations indicate that exposure to PFAAs results in immunomodulation. The mechanisms by which immunomodulation occur have not been elucidated, although ligation of PPAR-alpha, and to some extent PPAR-gamma, is assumed to explain some of the immune changes associated with PFAA exposure. However, increasing experimental evidence suggests that while PPAR-alpha receptor activation is important for mediation of inflammatory responses and many non -immune parameters, several immune endpoints are affected by PFAA exposure whether or not a functional PPAR-alpha is present. In addition, host phenotype also may impact the effects of PFAA exposure on immune responses. Two strains of PPAR-alpha knockout mice are generally available; one is on a 129 background and the other is on a B6 background. Initial studies with the 129 strain indicate that attenuation of antibody synthesis and decreases in lymphocyte cellularity and lymphoid organ weights observed in wild -type animals do not occur to the same degree in the knockouts. However, the 129 strain appears to be relatively insensitive to the effects of PFAAs, specifically perfluorooctanoic acid, on antibody synthesis and lymphoid organ weights. Therefore, PPAR-alpha involvement in PFAA- 31 DEQ-CFW 00000670 mediated reductions in antibody synthesis or lymphoid organ weights is suspect in this strain of mouse. Studies with the B6 strain, a strain that seems very sensitive to effects of PFAAs on antibody synthesis, indicate that similar levels of antibody suppression occur in the wild -type and PPAR-alpha knockouts. Therefore, PPAR-alpha involvement in PFAA-mediated reductions in antibody production and lymphoid organ weights in the B6 strain of mouse suggests that a functional PPAR-alpha receptor is not necessary. The role of PPAR-alpha in PFAA-induced immnomodulation indicates that while adaptive immunity is susceptible PFAA exposure, the mechanism may not include mediation by receptor activation and may be modulated by host phenotype. 32 DEQ-CFW 00000671 U.S. EPA PFAA DAYS III SYMPOSIUM POSTERS P1—Nomenclature and Acronyms for Highly Fluorinated Substances Polymers and Chemicals R.C. Buck,' J. Franklin,2 and many very helpful collaborators 'E.I. du Pont De Nemours & Co., Inc, Wilmington, DE; 2CLF-Chem Consulting SPRL, Grez-Doiceau, Belgium The discovery of fluorinated substances such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in the environment has prompted an expansive increase in research and publications on these and related substances. Concomitantly, authors have created new words and acronyms to describe these and like substances. Unfortunately this has resulted in multiple terms and acronyms that describe the same substances and broad terms to describe a wide array of substances that may in fact not really be like one another. For example, what does the term "PFC" describe? As a result, an effort has been undertaken by a workgroup within Plastics Europe in collaboration with a number of academic and government researchers to agree upon the definition and use of terms and acronyms that clearly and specifically describe highly fluorinated substances of many types. The goal of this effort is adoption and use of these terms and acronyms. The poster will present this work in its current form and solicit input and reflection from the conference participants. P2—EcoTox and PK Findings for Ammonium Perfluorohexanoate (APFHx) Hiroyuki lwai Daikin Industries, Ltd., Nishi Hitotsuya, Settu, Osaka, Japan Fish, Early Life Stage Toxicity Test to Oncorhynchus mykiss (Rainbow Trout) The objective of the study was to establish the effect of ammonium perfluorohexanoate (APFHx) on the growth and development of embryos and larvae of the freshwater fish species Oncorhynchus mykiss (Rainbow trout) in a Fish Early -Life Stage Toxicity Test. The test was conducted with a flow -through test design. The validity criterion for hatching success was satisfied. The NOEC and LOEC for hatching success, post -hatch larval survival, total fish length and fish weight were 9.96 and >9.96 mg/L respectively. There were no dose related abnormalities recorded during the test. The Excretion and Tissue Distribution of [14C]- APFHx in the Mouse and the Rat Following a Single and Multiple Oral Administration at 50 mg/kg. The objective of this study was to examine excretion patterns and rates for APFHx following single and multiple (14 day) oral doses at 50 mg/kg to male and female mice and rats. The test substance was a [14C]-labeled version of APFHx. Tier.1 Single oral dose Irrespective of gender or species, following a single oral administration, total radioactivity excretion was rapid, with mean recoveries of over 90% of the dose at 24 h post dose. The major route of elimination was via the urine (percentage means between 73.0-90.2% of the dose), followed by the feces (percentage means between 7.0-15.5% of the dose). Elimination via expired air was negligible. Tier.2 Multiple (14 daily doses) oral dose A multiple (13 daily doses) oral administration of APFHx was followed by a single oral administration of [14C]- APFHx. Irrespective of gender or species, total radioactivity excretion was rapid, with mean recoveries of over 90% of the dose administered (and with mean values >95% of the ultimately recovered material) at 24 h post dose. The major route of elimination was via the urine (percentage means between 77.8-83.4% of the dose), followed by the feces (percentage means between 9.6-12.9% of the dose). 33 DEQ-CFW 00000672 P3-Inter-laboratory Comparison Update: Perfluorinated Contaminants in NIST Standard Reference Materials Jessica L. Reiner,' Jennifer M. Keller' Craig M. Butt,2 Scott Mabury,2Jeff Smal1,3 Derek Muir,3 Amy Delinsky 4 Mark Strynar4 Rania Farag,5 Sathi Selliah,5 William K. Reagen,6 Michelle Malinsky,6 Christiaan Kwadijk,� Dale Hoover, John W. Washington,9 and Michele M. Schantz10 'Analytical Chemistry Division, National Institute of Standards and Technology, Charleston, SC; 2University of Toronto, Toronto, ON, Canada; 3Water Science and Technology Directorate, Environment Canada, Burlington, ON, Canada; 4US Environmental Protection Agency, Research Triangle Park, NC; 5Ontario Ministry of the Environment, Toronto, ON, Canada; 6Environmental Laboratory, 3M Company, St. Paul, MN; 7Wageningen IMARES, Ijmuiden, The Netherlands; 6Axys Analytical Services Ltd., Sidney, BC, Canada; 9US Environmental Protection Agency, Athens, GA; 90Analytical Chemistry Division, National Institute of Standards and Technology, Gaithersburg, MD Standard Reference Materials (SRMs) are homogeneous, well -characterized materials that are used to validate measurements and improve the quality of analytical data. The National Institute of Standards and Technology (NIST) has a wide range of Standard Reference Materials (SRMs) that have values assigned for legacy organic pollutants. These SRMs can serve as target materials for method development and measurement for contaminants of emerging concern. Since inter -laboratory comparison studies have shown considerable disagreements when measuring perfluorinated compounds (PFCs), future analytical measurements will benefit from the characterization of PFCs in SRMs. NIST and 11 collaborating laboratories have been measuring PFCs in a variety of SRMs, including human serum (SRMs 1957, 1958), human milk (SRMs 1953, 1954), bovine liver (SRM 1577c), fish tissue (SRMs 1946, 1947), mussel tissue (SRM 2974a, 1974b), sediment (SRMs 1941 b, 1944), sludge (SRM 2781), soil (SRM 2586) and dust (SRMs 1648a, 1649b, 2786, 2787, 2585) with the goal of eventually assigning reference or certified concentrations. As part of this informal inter -laboratory comparison study, SRMs 1957 and 1958 have recently been assigned reference values for seven and four PFCs, respectively. Inter -laboratory measurements for other SRMs are ongoing. Preliminary measurements in SRMs show an array of PFCs, with perfluorooctane sulfonate (PFOS) being the most frequently detected. Preliminary average PFOS concentrations (along with RSD, and number of labs reporting) are 5.07 ng/g dry mass (RSD = 10%, n=3) for SRM 1577c; 2.91 ng/g wet mass (RSD = 51%, n=6) for SRM 1946; 6.94 ng/g wet mass (RSD = 46%, n=6) for SRM 1947; 2.73 ng/g dry mass (RSD = 40%, n=2 plus one lab reporting <1.6 ng/g dry mass) for SRM 2974a; below detection (n=2) for SRM 1974b; 0.75 ng/g dry mass (RSD = 44%, n=5 plus one lab reporting <0.8 ng/g dry mass) for SRM 1941 b, 2.62 ng/g dry mass (RSD = 34%, n=5 plus one lab reporting <0.5 ng/g dry mass) for SRM 1944; 4.44 ng/g dry mass (RSD = 31 %, n=3) for SRMs 2586; 274 ng/g dry mass (RSD= 31 %, n=3) for SRM 2781; 1843 ng/g dry mass (RSD = N/A, n=1) for SRM 2583, respectively. PFOS measurements are quite variable among labs, suggesting method improvements are needed prior to assigning reference values in NIST SRMs. These reference materials are needed to provide quality assurance measurements for various laboratories throughout the world and work is ongoing to provide reliable measurements. P4-Distribution of PFCs in Wildlife in China and Toxicology of PFCs Hongxia Zhang, Jianshe Wang, and Jiayin Dai Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, P. R. China PFCs have garnered intense scientific and regulatory interest due to their extraordinary environmental persistence and bioaccumulation tendencies. Our research interests focus on its distribution, and sources, as well as the toxic effects and mechanism on wildlife and humans. 1. The pattern of PFCs in wildlife species Discharge of municipal wastewater treatment plants (WWTPs) may be an important source of organic contaminants such as PFCs in aquatic environments. PFCs were measured in zooplankton and five fish species collected from Gaobeidian Lake, which receives discharge from a WWTP in Beijing, China. PFOS occurred at the greatest concentrations in five fish species detected. PFDA was the second dominant PFC in fish samples. A positive linear relationship was observed between PFOS concentrations and 34 DEQ-CFW 00000673 trophic level (Environ. Pollut., 2008, 156, 1298-1303). We analyzed blood PFC levels in Amur tigers, giant pandas, and red pandas from different captive centers situated in industrialized and nonindustrialized regions of China (Environ. Sci. Technol., 2006, 40, 5647-5652). PFC concentrations were significantly higher in tigers from the industrial areas than those from non -industrialized regions. PFOS was the predominant compound in all samples measured, and the levels of PFOS increased with age in the tigers regardless of the industrial/non-industrial background (Environ. Sci. Technol., 2008, 42, 7078-7083; Chemosphere, 2008, 73, 1649-1653). These results confirm our hypothesis that captivity in industrialized areas increases PFC levels in endangered species. These data also suggest that PFC accumulation persists and even increase with continued use of PFCs in China. 2. The toxicological effects of PFCs (1) Hepatic effects of PFCs We found that acute PFC exposure induced oxidative stress and alteration of mitochondrial function in the livers of female zebrafish. In addition, this exposure led to swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis in the liver in these fish. These results demonstrated that turbulence of fatty acid beta -oxidation and oxidative stress responses were involved in the PFC-induced hepatotoxicity. Furthermore, PFC exposure also altered the transcriptional expression of CYPs, such as CYP1A and CYP3A (Aquatic toxicology, 2008, 88, 183-190; 89, 242-250; Comp. Biochem. Phys., C, 2009, 150, 57-64 ). To further assess the effects of PFC in fish and identify the mode of action of the observed toxicity, a custom cDNA microarray was applied to hepatic gene expression profile analysis in male and female rare minnows. In addition, two-dimensional electrophoresis coupled with mass spectrometry was used to identify proteins differentially expressed in the livers following PFCs exposure. The results from these toxicogenomic and toxicoproteomic approaches suggested that the mechanism of action of PFCs may involve interfering with intracellular fatty acid transport and oxidative stress pathways (Toxicol. Appl. Pharmacol., 2008, 226, 285-297; J. Proteome Res., 2008, 7, 1729-1739). Since the metabolic network is downstream of both gene expression and protein synthesis, metabonomics technology has shown great promise for understanding toxin -induced endogenous metabolic responses and identifying novel toxicity biomarkers. Thus, NMR-based metabonomics were employed to investigate dose -dependent alterations in the metabolic profiles of serum, intact liver, and liver extracts in rats exposed PFDoA. PFDoA exposure led to hepatic lipidosis, which was characterized by a severe elevation in hepatic triglycerides and a decline in serum lipoprotein levels. The identified transcriptomic changes in fatty acid homeostasis corroborated these results (J. Proteome Res., 2009, 9, 2882-2991). (2) Immunological effects of PFCs Exposure to PFCs led to a decrease in the weight of the lymphoid organs. Both cell cycle arrest and apoptosis were observed in the spleen and thymus in rodents. In the thymus, PFCs mostly modulated CD4+CD8+ thymocytes, whereas the F4/80+, CD11 c+, and CD49b+ cells were the major targets in the spleen. The production of interleukin (IL)-4 and interferon-y by splenic lymphocytes was impaired dramatically (Toxicol. Sci., 2008, 105, 312-321). The levels of cortisol and adrenocorticotrophic hormone in sera were increased. Together, these results suggested that PFNA exerted toxic effects on lymphoid organs and these effects may result from the activation of PPARa and PPARy, and the hypothalamic - pituitary -adrenal axis. Histopathological examination revealed dose -dependent increases in thymocyte apoptosis. Phospho-p38 was significantly enhanced, whereas phospho-IKBa remained consistent (Toxicol. Sci., 2009, 108, 367-376). (3) Reproductive effects of PFCs In teleosts, circulating sex steroid levels can be affected significantly by exposure to compounds that interfere with the endocrine system. When the freshwater teleost rare minnow was exposed in PFOA, the ovaries of females underwent degeneration, similar to that reported for other fish species exposed to environmental estrogens. The development of oocytes in testes exposed to PFOA also provided evidence of estrogenic activity in males. A significant increase of vitellogenin (VTG) expression was observed in the livers of both mature males and females following exposure to PFOA (Environ. Toxicol. Chem., 2007, 26, 2440-2447). To address the effects of PFCs exposure on male reproduction, testes ultrastructure, testosterone levels, and steroidogenic gene expression were investigated in rats exposed to PFDoA. Absolute testis weight was diminished, while the relative testes weight was markedly increased. 35 DEQ-CFW 00000674 Luteinizing hormone and testosterone were significantly decreased in these exposed animals. Leydig cells, Sertoli cells, and spermatogenic cells exhibited apoptotic features, and PFCs exposure resulted in significant declines in mRNA expression of several genes involved in cholesterol transport and steroid biosynthesis (Toxicol. Sci., 2007, 98, 206-215; Toxicol. Lett., 2009, 188, 192-200). Furthermore, we also demonstrated that PFDoA inhibit steroidogenic acute regulatory protein (StAR) expression at the mRNA and protein levels but failed to affect the mRNA levels of PBR, P450scc, or 3(3-HSD in vitro. In female, PFCs did not affect the endocrine status of pubertal rats, however, at higher doses, this exposure impacted estradiol production and the expression of some key genes responsible for estrogen synthesis (Reprod. Toxicol., 2009, 27, 352-359). In addition, PFCs exposure led to spermatogenic cell apoptosis in rat testis and caused a dose -dependent increase of apoptotic cell numbers. Expression of Fas and Bax mRNA levels were upregulated significantly, and Bcl-2 mRNA level was downregulated markedly following exposure to PFCs. A dose -dependent increase in active caspase-8 was observed, although no significant changes to active caspase-9 were observed (Toxicol. Lett., 2009, 190, 224-230). Thus, the apoptosis observed in spermatogenic cells following PFC exposure in rats was probably associated with the Fas death receptor -dependent apoptotic pathway. P5—Simultaneous Monitoring of Matrix Interferents During the Analysis of Perfluorinated Compounds in Tissue with a Novel Dual Scan-Mrm Approach Peter Hancock,' Paul Silcock,' Anna Karrman,2 Keith Worrall,'Bert van Bavel,2and Joe Romano3 Waters Corporation, Manchester, UK. 2MTM Research Centre, School of Science and Technology, Orebro University, Orebro, Sweden; 3 Waters Corporation, Milford, MA Perfluorinated compounds (PFCs) have been determined over the last ten years in an array of matrices by various techniques including liquid chromatography tandem quadrupole mass spectrometry (LC/MS/MS).1 More recently UltraPerformance LC (UPLC) has been introduced as a technique utilized in the analysis of PFCs and has offered rapid analysis whilst preserving separations.2 The ability of laboratories to successfully measure PFCs in various matrices has improved greatly, with some of the success attributed to the continuous improvement in data quality with advances in instrumental technology. Advances in LC/MS/MS instrumental performance have largely been focussed on the sensitivity of Multiple Reaction Monitoring (MRM) mode to satisfy the need for increasingly lower detection limits. While this is clearly a priority for this type of instrumentation there has previously been limitations in acquiring important qualitative information from a sample in a single injection. This information can be of high value when analysing ultra trace level contaminants in difficult sample matrices such as tissues when trying to further improve the quality of methods. The potential of a novel acquisition mode, Dual Scan-MRM, in LC/MS/MS instrumentation applied to the analysis of PFCs will be discussed. Full scan background matrix data was simultaneously acquired with quantitative MRM data using Dual Scan-MRM. This was utilised in combination with rapid 5 minute UPLC separation for the analysis of salmon liver from unknown locations in Norway. Dual Scan-MRM acquisitions allowed correlations between background matrix components and analytical problems to be observed, particularly for indigenous bile acids in salmon liver. Additional evidence for these compounds were obtained using product ion scanning which indicated the presence of deoxytaurocholate isomers co -eluting with PFOS. Further work is required to manage the negative effects of matrix in PFC analysis but continuously monitoring sample background using a Dual -Scan MRM approach can lead to more information about the challenges posed by each individual sample. This is a novel intra-sample quality control (QC) check that has the potential to help improve quality within PFC analysis and is made possible by next generation instrumentation. 1. Jahne A., Berger U. J. Chrom. A 2009;1216:410-421 2. Jenkins T., Eilor N., Twohig., Worrall K., Kearney G., 2005;Organohalogen Compounds 76 244-247 3. LindstrOm G., Karrman A,. van Bavel B. J. Chrom. A 2009;1216:394-400 4. van Leeuwen S.P.J, Swart C.P, van der veen I., de Boer J. J. Chrom. A 2009;1216:401-409 36 DEQ-CFW 00000675 P6—Measurements of Perfluorinated Compounds in Plasma of Northern Fur Seals (Callorhinus ursinus) and a Preliminary Assessment of Their Relationship to Peroxisome Proliferation and Blood Chemistry Parameters F/anary, Jocelyn R., Reiner, Jessica L., He/ke, Kristi L., Kucklick, John R., Gulland, Frances M. D., and Becker, Paul R. National Institute of Standards and Technology/Medical University of South Carolina, Charleston, SC Perfluorinated compounds (PFCs) are known to exhibit toxicological effects in laboratory animals and may pose a risk of adverse effects in marine mammals. In northern fur seals (Callorhinus ursinus) only perfluorooctane sulfonate (PFOS) has been analyzed. In this study we report concentrations of thirteen perfluorinated compounds measured in northern fur seal plasma from animals harvested on St. Paul Island, Alaska in 2006 and 2007. Liquid chromatography/tandem mass spectroscopy (LC/MS/MS) was used to perform the analysis. Perfluoroundecanoic acid (PFUnA) was the most abundant compound with a median concentration of 5.5 ng/g ranging from 1.2 to 16.8 ng/g, followed by perfluorononanoic acid (PFNA) at 3.3 ng/g (1.3 to 9.6 ng/g) and PFOS at 3.0 ng/g (0.9 to 18.6 ng/g). Interestingly, PFOS is not the most abundant compound as it is in most environmental studies, suggesting a different source or preferential metabolism of the C11 and C9 carboxylic acid compounds. The results reported here demonstrate that several perfluorinated compounds are at measurable quantities in the northern fur seal, with some PFCs being measured for the first time in this species. We also determined that peroxisome counts and blood chemistry parameters were not significantly correlated to concentrations of perfluorinated compounds measured in the plasma. This suggests the levels of PFCs in this population are too low to induce peroxisome proliferation or to affect other blood chemistry markers. Currently, analyses are being performed on liver and kidney samples from the same animals as the plasma to help understand the body distribution of PFCs in northern fur seals. P7—Determination of Perfluorochemicals in Milk Using Liquid Chromatography — Tandem Mass Spectrometry Wendy M. Heiserman, Gregory O. Noonan, Paul South, Timothy H. Begley, and Gregory W. Diachenko Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD Perfluorochemicals (PFCs) are used in the manufacturing of and applied to a large array of industrial and consumer products including cookware, upholstery, clothing, and food packaging. This wide scale industrial use of PFCs has led to their global distribution in the environment, flora and fauna. A number of epidemiological studies have detected PFCs in the blood, urine and breast milk of the general population; however the routes of exposure have not been well quantified or characterized. While foods are clearly a source of human exposure to PFCs, it is unclear what role food packaging and processing plays in altering the PFC concentrations in foods. The quantification of PFCs in raw foods is the first step in understanding the role of food processing and packaging in human exposure to PFCs. This presentation will discuss method development and validation for the detection of PFCs in milk sampled over a large geographical range of the United States. Values determined by liquid chromatography -tandem mass spectrometry will be reported for PFC concentrations in raw and processed milk. Analytical method development investigated different method issues including but not limited to the difference between acid and base processing of the milk, and separation of perfluoroctane sulfonate isomers and taurodeoxycholic acid. Findings will be compared with other investigations of PFC exposure from food sources. P8—Genotoxicity of Perfluoro Carboxylates (C5-C12) Detected by Comet Assay Shuji Tsuda,I Itaru Sato,' Kosuke Kawamoto,', Haruna Goto,' Kazunori Oami,2 Me Jin,3 Norimitsu Saito,4 and Shuhei Tanaka5 5Iwate University, ZUniversity of Tsukuba, 3Dalian University of Technology, 4RIEP of Iwate Prefecture, Kyoto University Genotoxicity of perfluoro carboxylates (PFCA, C5-C12) was studied using in vivo comet assay in paramecia and mice in relation to intracellular reactive oxygen species (ROS), 8-hydroxydeoxyguanosine 37 DEQ-CFW 00000676 (80H-dG) and PPAR alpha. All the PFCAs tested caused DNA damage detected by alkaline (pH 13) comet assay in paramecia after 24 hr incubation. PFCAs with carbons 5-8 and 9-12 showed DNA damage at no less than 100 and 10 micro M, respectively. In mouse alkaline comet assay, PFOA (C8) at the maximum tolerated dose ( MTD) of 120 mg/kg showed DNA damage in the liver after 3 day consecutive oral administration, but neither PFHA (C6 ) at the same dose (120 mg /kg)) nor PFNA( C9 ) at its MTD (40 mg /kg) caused DNA damage. The PFOA-induced DNA damage was detected in alkaline (pH 13) comet assay, but not at pH 12.1, suggesting that the DNA damage consists of alkaline labile sites (such as AP site) but not strand breaks. The PFOA-induced DNA damage was accompanied by increase in ROS, but not in 80H-dG. Incubation with glutathione (GSH) at 100 micro M abolished the PFOA-induced DNA damage, while leaving the DNA damage still present. Incubation with GW6471 (PPAR alpha antagonist) at 3 micro M abolished the PFOA-induced DNA damage. In conclusion, PFCAs even with shorter carbon chains of C6 or less have genotoxicity. PFOA-induced DNA damage might not be directly caused by intracellular ROS, but related to PPAR alpha agonistic mode of action. P9—Statistically-Based Sampling and Analysis of Fish Tissue for Perfluorinated Compounds in U.S. Urban River Segments and Great Lakes Waters Leanne Stahl,' John Wathen,' Tony Olsen,2 Blaine Snyder,3 and Chip McCarty4 'U.S. EPA, Office of Water, Office of Science and Technology, Washington, DC; 2U.S. EPA, Office of Research and Development, Western Ecology Division, Corvallis, OR; TetraTech Inc., Fairfax, VA; 4CSC, Inc., Alexandria, VA Fish tissue is an effective integrator of the presence of a variety of persistent contaminants that occur in water. Many such substances both organic and inorganic (e.g. Hg and PCBs), have been observed to bioaccumulate in fish tissue to concentrations many orders of magnitude higher than their respective water column concentrations. In separate studies of 1) —150 U.S. river segments randomly -selected in urban areas and 2) —150 randomly- selected U.S. Great Lakes locations (30/lake) within 10 km of WWTP outfalls, samples consisting of fillets from 3-5 fish of controlled uniform species and length are being analyzed for a suite of 13 perfluorinatcd compounds including PFOS, PFOA, and other PFCs of various carbon -chain lengths, along with total mercury. Other analytes variously include pharmaceuticals, synthetic musks, PBDEs, and PCBs and selected pesticides (rivers only). The studies are collaborations between EPA's Office of Water, Office of Research and Development, and Great Lakes National Program Office (Great Lakes study) and supporting contractors as part of the Office of Water's continuing National Aquatic Resource Surveys. P10—Comparisons Between Free Thyroxine Levels Measured by Analogue and Equilibrium Dialysis Methods, in the Presence of PFOS and PFOA Tony Fletcher, Maria -Jose Lopez -Espinosa, Nicola Fitz -Simon, and Ben Armstrong Department of Social and Environmental Health Research (formerly the Public and Environmental Health Research Unit), London School of Hygiene and Tropical Medicine, London, UK Background. It has been suggested that some polyfluorinated compounds (PFCs) may alter thyroid function. However, a study in rats highly exposed to pert] uorooctanesulfonic acid (PFOS) reported that apparent associations may be due to negative bias in analogue methods, since free thyroxine (FT4) and labelled FT4 analogues may be displaced from the serum and assay binding proteins in the presence of PFOS; and the use of dialysis instead of analogue methods has been recommended, to determine FT4 levels in presence of PFOS [1]. This observation has led to concern that this phenomenon may lead to bias in reported associations between PFOS or PFOA (perfluorooctanoic acid) and thyroxine. Objectives. The objectives of the present study were: 1) to estimate the degree to which any differences in human FT4 measurements by dialysis and analogue methods were associated with PFOS or PFOA; and 2) to estimate bias in the relationship between analogue FT4 and PFOS in humans that would follow from any such association or that found in the study with rats. M DEQ-CFW 00000677 Methods. Serum from 50 participants from the C8 Science Panel Study was measured for FT4 by ele ctrochemi luminescence immunoassay [ECLIA] (an analogue method) and high pressure liquid chromatography/mass spectrometry [HPLC/MS] (a direct dialysis mass spectrometry method). PFOA and PFOS were measured in serum using liquid chromatography separation with detection by tandem mass spectrometry. We fit linear regression models to estimate the difference between analogue and dialysis measurements in relation to PFOS and PFOA in the 50 participants; and the difference between analogue and dialysis methods in relation to PFOS in treated and control rats. Results. In the sample of 50 individuals, mean (sd) levels of PFOA and PFOS were 117.44 (307.16) ng/mL and 10.50 (6.19) ng/mL. Mean FT4 was 1.23 (0.20) ng/dL by analogue and 1.24 (0.27) by dialysis. Regressing the difference between FT4 measures on either PFOA or PFOS yielded slopes close to zero. Using the rat data, the analogue measurement underestimated the dialysis measurement by-0.0004 (CI: -0.0002,-0.0006) for a change of 20 ng/mL PFOS. This is a trivial difference (<0.05% of the mean) and would be in effect impossible to detect. Conclusion. These findings do not suggest a PFC exposure related difference between the two methods used to measure FT4 at exposure levels in this population. [1] Chang et al. Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS).Toxicology. 2007;234(1-2):21-33. P11—Investigation of Pfcs Pollution in the Terrestrial Environment of Japan Using Dragonfly as Biomonitoring Tool Mitsuha Yoshikane ,' Sumiko Komori,', Miyako Kobayashi,' Miyuki Yanai,1 Tetsuyuki Ueda ,2 Takeshi Nakano,3 and Yasuyuki Shibata' 'Time Capsule Team, Environmental Chemistry Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan; 21shikawa Prefectural University, Nonoichi, Ishikawa, Japan; 3Hyogo Prefectural Institute of Environmental Sciences, Kobe, Hyogo, Japan Over the past few years, we have studied the potential of dragonflies as a tool for monitoring of perfluorinated compounds (PFCs) pollution in terrestrial environment. We found that mature male of several common species apparently showed comparable data each other, suggesting that combined use of them will be appropriate for the terrestrial monitoring. In order to reveal the PFCs pollution status in terrestrial environment, PFCs levels in several species of dragonfly collected from 100 sites in more than half of the prefectures of Japan were analyzed. The collected dragonfly was analyzed by strong alkaline digestion method combined with LCMSMS. (Yoshikane et al., Organohalogen Compounds, 68, 2063 (2006)) The PFCs, including perfluorooctane sulfonate (PFOS) and perfluoroalkylcaboxylic acids (PFCAs) (C8—C12), were analyzed by using 13C- labeled surrogates as Internal Standards. Elevated levels of PFCs were found in densely populated / industrialized areas, i.e., Kanto and Kinki. In addition, relatively higher concentrations of PFCs were detected in some areas, such as Hokuriku, where known or suspected sources of PFCs are present. On the other hand, there are differences in PFCs compositions between Kanto and Kinki areas; i.e., PFOS is dominant in dragonfly caught in many sites in Kanto, while dragonfly caught in Kinki area accumulated PFCAs with longer chain (such as PFuDA and PFdDA) as major compounds. There differences coincide well with the results of river water analysis, supporting our view that dragonfly is a useful tool for biomonitoring terrestrial environment. 39 DEQ-CFW 00000678 P12—Male Reproductive System Parameters in a Two -Generation Reproduction Study of Ammonium Perfluorooctanoate in Rats and Human Relevance Raymond G. York,' Gerald L. Kennedy, Jr.,2 Geary W. Olsen ,3 and John L. Butenhoff3 1WIL Research Laboratories, Ashland, OH; 'DuPont Company, Wilmington, DE; 33M Company, St. Paul, MN Ammonium perfluorooctanoate (ammonium PFOA) is an industrial surfactant that has been used primarily as a processing aid in the manufacture of fluoropolymers. The environmental and metabolic stability of PFOA, together with its presence in human blood and long elimination half-life, have led to extensive toxicological study in laboratory animals. Two recent publications based on observations from the Danish general population have reported: 1) a negative association between serum concentrations of PFOA in young adult males and their sperm counts; and 2) a positive association among women with time to pregnancy. A two -generation reproduction study in rats was previously published (2004) in which no effects on functional reproduction were observed at doses up to 30 mg ammonium PFOA/kg body weight. The article contained the simple statement: "In males, fertility was normal as were all sperm parameters". In order to place the recent human epidemiological data in perspective, herein are provided the detailed male reproductive parameters from that study, including sperm quality and testicular histopathology. Sperm parameters in rats from the two -generation study in all ammonium PFOA treatment groups were unaffected by treatment with ammonium PFOA. These observations reflected the normal fertility observations in these males. No evidence of altered testicular and sperm structure and function was observed in ammonium PFOA-treated rats whose mean group serum PFOA concentrations ranged up to approximately 50,000 ng/mL. Given that median serum PFOA in the Danish cohorts was approximately 5 ng/mL, it seems unlikely that concentrations observed in the general population, including those recently reported in Danish general population, could be associated causally with a real decrement in sperm number and quality. P13—Perfluoroalkyl Compounds in the Eggs of Four Species of Gulls (Larids) from Breeding Sites Spanning Atlantic to Pacific Canada Wouter A. Gebbink,',Z Neil Burgess,3 Louise Champoux,4 John E. Elliott,5 Craig E. Hebcrt,1 Pamela Martin,e Mark Wayland,' D.V. Chip Weseloh,8 Laurie Wilson,5 and Robert J. Letcher' 2 'National Wildlife Research Centre, Science and Technology Branch, Environment Canada, Carleton University, Ottawa, ON, Canada; 2Department of Chemistry, Carleton University, Ottawa, Ontario, Canada; 3Environment Canada, Science and Technology Branch, Mount Pearl, Newfoundland, Canada; 4Environment Canada, Science and Technology Branch, Quebec City, Quebec, Canada; 5Pacific Wildlife Research Centre, Science and Technology Branch, Environment Canada, Delta, British Columbia, Canada; 6Environment Canada, Science and Technology Branch, Burlington, Ontario, Canada; Prairie and Northern Wildlife Research Centre, Environment Canada, Science and Technology Branch, Saskatoon, Saskatchewan, Canada; 8Canadian Wildlife Service, Environment Canada, Downsview, Ontario, Canada In the present study we investigated the Pan -Canadian spatial distribution of perfluoroalkyl compounds in the eggs of several species of gulls. Eggs from Glaucous -winged gull, California gull, Ring -billed gull or Herring gull (n=10 eggs for each location)) were collected in 2008 from urban sites (e.g. colonies near Victoria, BC; Calgary, AB; Toronto, ON; Montreal, QC; Quebec City, QC; St John's, NL) and non -urban sites (e.g. colonies on Lake Winnipeg, MB; Lake Superior, ON; Gulf of St. Lawrence, QC and Sable Island, NS). The perfluorosulfonate (PFSA) pattern consisted of the C6, C8, CIO chain lengths and was dominated by PFOS (>90% of FPFSA concentration) regardless of collection location or gull species. Depending on the species and location, C6 to C15 perfluorocarboxylic acids (PFCAs) were detected in the eggs with the longer chain length PFCAs (CtO - C14) dominating the pattern in all cases. The highest ZPFSA and ZPFCA concentrations were found in herring gull eggs collected in southern Ontario (Toronto) and western Quebec (Montreal) compared to the other locations and gull species. Of the eggs from the maritime province locations, the highest levels of FPFSA and FPFCA were found on remote Sable Island in the Atlantic Ocean relative to the colonies near St John's, Newfoundland and Saint John, New Brunswick. Perfluorosulfonamide (PFOSA), a possible PFOS precursor was infrequently detected at low concentrations without any apparent trend. Fluorotelomer unsaturated carboxylic acids (6:2, 8:2 and all DEQ-CFW 00000679 10:2 FTUCAs) were also found at low concentrations, suggesting that these compounds were possible precursors to PFCAs of corresponding chain length. In general, these results showed that relative to more remote locations, 7_PFSA and ZPFCA concentrations were higher in gull eggs from colonies near urbanized areas. This reflected the importance of urban sources in regulating the degree of PFC contamination of aquatic and terrestrial food webs used by gulls. P14—Histopathologic Changes in the Uterus, Cervix and Vagina of Immature CD- 1 Mice Exposed to Low Doses of Perfluorooctanoic Acid (PFOA) in the Uterotrophic Assay D. Dixon," A.B. Moore, 'a E. Wallace' la E.P. Hines, 2 E.A. Gibbs-Flournoy,3 J. Stanko, la R. Newbold, lb W. Jefferson,'° and S.E. Fenton la la Cellular and Molecular Pathology Branch, NTP, 'bLaboratory of Molecular Toxicology, NTP and the 'OLaboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC; 2Environmental Media Assessment Group, NCEA, NHEERL, ORD, U.S. EPA, RTP, NC; 3SSB Program, University of North Carolina, Chapel Hill, NC PFOA is a synthetic perflourinated compound that does not occur naturally in the environment, yet is a global contamination problem and a public health concern. Recent studies reported that PFOA increased the activity of estrogen -responsive genes in fish, and that PFOA treatment upregulated protein levels of estrogen receptor alpha (ERa) and proliferating cell nuclear antigen (PCNA) in the mammary glands of wild -type C57B1/6 and peroxisome proliferator—activated receptor a (PPARa knock -out mice. Because of these findings, and the fact that PFOA induced developmental mammary gland delays at low doses, we were interested in assessing the estrogenic or anti -estrogenic potential of PFOA on the immature mouse uterus using a standardized uterotrophic assay and evaluating the histomorphology of the uterus, cervix and vagina following treatment. Timed -pregnant CD-1 dams (N=17) delivered litters that were equalized to 10 female pups within 18 hr of birth. Early on postnatal day (PND) 18, pups were weaned, weighed, and assigned to treatment groups of equal weight. That same day, pups were treated by oral gavage with PFOA (0, 0.01, 0.1, or 1 mg PFOA/kg body weight (BW) with or without 17-R estradiol in corn oil (E2, 500 pg/kg, s.c.). All mice not administered E2 received a corn oil vehicle s.c. injection. Mice were necropsied 24 hr after the third dose (on PND 21). Uteri were removed at the utero-cervical junction, weighed, and fixed in 10% neutral buffered formalin and routinely paraffin embedded. In a second block of the study, identical to the first, the entire reproductive tract of the females was removed and fixed as stated. Five pm sections were cut, stained with hematoxylin and eosin and observed for histolopathologic changes using light microscopy. Reproductive organs of the E2-treated mice showed several characteristic changes, such as edema of the endometrium, increased epithelial layers of the uterine and vaginal lumens and glands, and keratinization of the vaginal and cervical epithelium. No anti -estrogenic effects were found by co -administration of PFOA with E2. However, PFOA-animals showed minimal increases in endometrial stromal cells and glandular epithelium with mild endometrial edema in addition to focal vaginal mucification, but not keratinization. A special stain to evaluate collagen deposition in the uterus, cervix and vagina after PFOA treatment is underway. Also, immunostains for PCNA and ERa/ERR and the progesterone receptor (PR) are in progress to confirm increases in endometrial stromal cells and glandular epithelium in the PFOA-animals, and to assess PFOA's regulation of steroid hormone receptors, respectively. This abstract does not necessarily reflect NIEHS policy. P15—Environmental Fate and Transport Modeling for Perfluorooctanoic Acid (PFOA) Emitted from the Washington Works Facility Hyeong-Moo Shin,' Veronica Vieira,2 P. Barry Ryan,3 Russell Detwiler,' Brett Sanders,' Kyle Steenland,34 and Scott Bartell' 'University of California -Irvine, Irvine, CA; 2Boston University, Boston, MA; 3Emory University, Atlanta, GA; 4C8 Science Panel, Atlanta, GA Background/Aims: Perfluorooctanoic acid has been found in environmental samples near the Washington Works facility in Ohio and West Virginia. This contamination is believed to have resulted primary from perfluorooctanoic acid emissions from the facility to the Ohio River and to the air, and from subsequent deposition and percolation of the particles through the vadose zone into the saturated zone. Pumping by 41 DEQ-CFW 00000680 industrial and municipal wells near the contaminated Ohio River and/or contaminated groundwater are thought to explain elevated well water concentrations observed in six municipal water districts. Our objective is to produce retrospective predictions for local air, surface water, and groundwater concentrations based on estimates of historic emission rates from the facility, physiochemical properties of PFOA, and local geologic and meteorologic characteristics. Methods: We relied on annual PFOA emission rates for air and the Ohio River from Washington Works for the period of 1951- 2008, and linked several environmental fate and transport models including AERMOD, PRZM3, BREZO, MODFLOW, and MT3D to simultaneously model PFOA air dispersion, transit through the unsaturated soil zone, surface water transport, and groundwater flow and transport. Many environmental samples are available since about 2000, including measurements of PFOA in groundwater, soil, and limited samples in surface water and air. We calibrated our linked fate and transport model to observed groundwater concentrations because those result from long-term transport and are less likely to be influenced by variations in short-term emission rates. Separate calibration constants ((p) were computed for each water district j by minimizing the least squared error, after choosing the best organic carbon partition coefficient (K,,) for all water districts from 9 different runs. Results: The value of Ko, that best predicted the observed well water concentrations was 0.845 L/kg. Comparing predicted and recently observed concentrations, the predicted water concentrations were within 2.1 times the average observed water concentrations for all six municipal water districts. The calibration constants (cps) for Belpre, Little Hocking, Old Lubeck, New Lubeck, Tuppers Plains, Mason County, and Pomeroy were 1.35, 2.00, 2.10, 1.65, 2.00, 0.55, and 0.70, respectively. Conclusion: Our linked fate and transport models predict recently observed municipal water concentrations reasonably well, and will be used to produce individualized retrospective exposure estimates for a variety of epidemiologic studies being conducted in this region. Keywords: Perfluorooctanoic Acid (PFOA), Environmental fate and transport models, Groundwater concentrations P16 Developmental Exposure of CD-1 Mice to PFOA Identifies the Mammary Gland as a Low Dose Target Tissue Madisa B. Macon,' Jason P. Stanko,2.3 and Suzanne E. Fenton2.3 'University of North Carolina Toxicology Curriculum, Chapel Hill, NC; 2US EPA, Toxicity Assessment Division, RTP, NC; 3NIEHS/NTP, Cellular and Molecular Pathology Branch, RTP, NC The surfactant perfluorooctanoic acid (PFOA) has become an environmental contaminant due to its widespread industrial applications. Previous studies by our laboratory indicated that exposure to 5 PFOA mg/kg/d during gestation delayed mammary gland development in exposed female offspring. To investigate the effects of low -dose PFOA exposure on the mammary gland, timed -pregnant CD-1 mice were orally dosed with 0.0, 0.01, 0.1, or 1.0 mg PFOA/kg body weight on gestation days (GD) 10-17. Litter size was equalized at birth and mammary glands were removed from pups on postnatal (PND) 1, 4, 7, 14, and 21 at each necropsy. When compared to controls, all exposed litters displayed aberrant mammary gland development. These effects were most prominent on PND 21 when all treatment groups were significantly different compared to controls for mammary gland score. At PND 21, the pups in the highest exposure group (1.0 mg/kg) displayed the most impaired mammary gland growth, with low mammary gland scores, low longitudinal and lateral epithelial growth, fewer visible branch points, and fewer visible terminal end buds. Although there was no effect on body weight due to treatment at any age evaluated, there was a difference in liver:body weight ratios in the 1.0 mg/kg dose group compared to controls evident from PND 4 to 14, which was likely due to significantly greater liver weights at PND 4 and 7 in the 1.0 mg/kg exposed pups. These data suggest that the lowest observable effect level of late gestational exposure to PFOA on liver:body weight ratio is 1.0 mg/kg, but is 0.01 mg/kg for mammary growth and developmental effects. The residual tissues from this study are currently being analyzed to determine the mechanistic pathways of low -dose PFOA toxicity in the mammary gland. This abstract does not necessarily reflect NIEHS policy. 42 DEQ-CFW 00000681 ONE HUNDRED-AND-FIFTITH MEETING OF THE SCIENCE ADVISORY BOARD (NCSAB) ON TOXIC AIR POLLUTANTS Proceedings of the April 28, 2010 Teleconference Dr. Starr called the meeting to order at 2:04PM. NCSAB members Drs. Thomas Starr, Woodhall Stopford, James Gibson, Man -Sung Yim, Elaina Kenyon, Wayne Spoo and Ivan Rusyn were in attendance. Connie Brower, DWQ; Larry Stanley, DWM; Drs. Jeff Engel and Doug Campbell, DHHS; Tom Mather, DAQ; Dr. Perry Cohn, NJ Consumer and Environmental Health Service; Dr. Gloria Post, NJ Dept. of Environmental Protection; and Dr. Gerry Kennedy and Michael Johnson, DuPont, were also in attendance. PFOA Literature Review Zhao et. al. (2010) — Abstract only - Dr. Spoo The study examined the underlying mechanism, independent of PPAR-a, resulting from exposure to PFOA in PPAR knockout and wild -type C5713I/6 mice. Mice were dosed at a level of 5 mg/kg. Exposure to "PFOA significantly increased serum progesterone levels in ovary -intact mice and also enhanced mouse mammary gland responses to exogenous estradiol." The results indicate that PFOA stimulates mammary gland development in C57BI/6 mice by promoting steroid hormone production in ovaries and increasing the levels of a number of growth factors (epidermal growth factor receptor, estrogen receptor, amphiregulin, hepatocyte growth factor, cyclin D1, and proliferating cell nuclear antigen) in mammary glands. Dr. Spoo was uncertain if an ovariectomized group was included in the study and will review the published paper. Dr. Starr asked if this study would have an impact on the draft risk assessment and Dr. Spoo responded that it should not. Additionally, Dr. Spoo could not recall reviewing any studies that observed impacts on estrogen or progesterone from exposure to PFOA in humans. Dr. Kennedy noted that Olsen's occupationally exposed cohort study examined impacts on hormones (e.g. estrogen, testosterone) from exposures to PFOA. The results indicated that there were no changes in hormone levels; however the study group was entirely male. Macon et.al. (poster presented at SOT 2010) — Dr. Kenyon This study investigated the effects of low -dose exposures to PFOA on mammary gland development in CD-1 mice. The mice were orally dosed on GD 10-17 with 0.0, 0.01, 0.1, or 1 mg/kg PFOA. Mammary glands were removed from pups on PND 1, 4, 7, 14, and 21. Aberrant mammary gland development was present in all litters with the most prominent effects on PND 21 for the highest exposure group. The authors report that "these data suggest that the lowest observable effect level of late gestational exposure to PFOA on liver: body weight ratio is 1.0 mg/kg, but is 0.01 mg/kg for mammary growth and developmental effects." Dr. Kenyon noted that this study could have implications regarding the draft risk assessment because it suggests a new LOAEL for developmental effects. The exposures in Lau et.al. (2006) ranged from 1 to 40 mg/kg PFOA for GD 1-17 in CD-1 mice and the results were delayed ossification of fetal forelimb and hindlimb phalanges (LOAEL = 1 mg/kg-day). Dr. Rusyn noted that this is a significant POD and may have an impact on the draft risk assessment, however, the study has not been published nor has it been peer reviewed and therefore should not be used at this time. He recommends using Lau et.al. (2006) POD. A NOAEL was not established for either study. Dr. Rusyn quoted an email from Dr. Fenton (4/16/10): "the serum concentrations are present on Macon's poster. At 0.01 mg/kg PFOA for the second half of pregnancy, we observed abnormal mammary gland development and the corresponding serum PFOA at the time shown is 16.5 ng/mL, but was nearly 300 ng/mL on PND 1 (24-hr after the dosing ceased). We used liver: body wt ratios within this study to confirm that we rcpoated work by others (Lau and Abbott) and we suggest that the. mammary gland is a more sensitive target tissue than the liver." He notes that the control level for Lau et.al. (2006) was 510 ng/mL, which is a 10-20 fold difference from that reported by Dr. Fenton. Dr. Kenyon voiced concerns regarding the differences in control levels and stated that this issue needs to be reconciled. Dr. Starr remarked that the serum levels presented by Macon et.al. may not have been corrected for background. Hines (2009) extrapolation to PFOA serum levels — Drs. Rusyn and Kenyon In an email from Dr. Kenyon (4/27/10) she states: "The basic question asked was what serum level of PFOA would correspond to the identified lower LOAEL of 0.01 mg/kg BW developmental exposure (for DEQ-CFW 00000682 GD 1-17) for various endpoints in female offspring, e.g. increased body weight gain, elevated serum leptin and serum insulin levels at mid-life (published manuscript). Also note abstract identifying same maternal LOAEL exposure level for GD 10-17 dosing for impaired mammary gland growth in female offspring (SOT 2010 abstract)." To elaborate on this question, the following issues become critical: (1) The appropriate serum dose metric for PFOA, i.e. what serum level and when, e.g. a. maternal average concentration (including when or over what interval)? b. fetal average concentration (including when or over what interval)? This comes down to the basic issue of what does the scientific evidence at hand suggest to us regarding the serum level of PFOA that is most closely related to driving the relevant biological events. (2) What do the data that we do have tell us? a. There is litter data for PFOA in serum in one of the posters for 0.01, 0.1 and 1.0 mg/kg maternal dose at PND 1, 4, 7, 14 and 21. It steadily declines in a linear manner with maternal dose after about Day 7 between dose groups for a given time point. I his is for a maternal exposure of GD10- GD17. b. Fenton et.al. (2009) gives dam serum PFOA for doses of 0.1, 1, and 5 mg/kg BW given on GD17 (single acute dose) at time points of GD18, PND1, PND4, PND8 and PND18, as well as levels in urine, mammary gland, and milk. In addition there are data on pup serum PFOA for PND 1, 4, 8,18 and whole pup PFOA on GD18 and PND1, 4,8 and 18. i. The trend is the same across doses for maternal serum PFOA (Fig 3A), i.e. increase through PND1, then decline through PND8, then increase at PND18. This U-shape is probably a function of hydrodilution, associated with increased blood and milk volumes. ii. Pups have a much higher serum PFOA on PND1 compared to dams (placental transfer), e.g. —225 vs. —325 for 0.1 mg/kg, —2000 vs. 3500 for 1.0 mg/kg and —10,000 vs. 16,000 for 5.0 mg/kg. Numbers are approximate because I am reading them off graphs and units are ng/mL serum. iii. Note that pup body burden increases through PND 8, probably as a function of lactational transfer. Dr. Starr asked if the effects are postnatal then would it be reasonable to think that the interactions are occurring during gestation? Dr. Kenyon acknowledged that the interactions were occurring during gestation but noted that lactational transfer was also occurring after birth that has not been quantified and should be considered as a source of uncertainty. Also, some of the effects observed are occurring in the female offspring at midlife. Dr. Kenyon notes that this study has a similar LOAEL (0.01 mg/kg) as Macon et.al. but the endpoint is different. Dr. Rusyn's summary of Hines et.al. (2009) from the March 31, 2010 NCSAB meeting states in part: "The authors report that the lowest exposures (0.01-0.3 mg/kg) significantly increased body weight, and serum insulin and /eptin (0.01-0.1 mg/kg) in mid-life after developmental exposure." Dr. Rusyn noted that in the Fenton et.al. (2009) paper the authors speculated that there was not only placental transfer but also lactational transfer occurring. Dr. Starr wondered if the doses were different from background exposures. Dr. Kennedy stated that he thought Dr. Lau's group was working on enhancing the study design to more clearly separate out the background concentrations. They are also investigating reproducibility and dosimetry. Dr. Kenyon noted that she also had questions regarding cross -species concordance. Dr. Kennedy went on to say that the endpoints observed in both studies seemed to be contradicting one another. The Zhao et.a/. study reports mammary gland and growth factor stimulation while the Macon et.al. study reports deficits in mammary gland development. Both agreed that the results of these studies required additional investigation, but Dr. Rusyn was not convinced that the effects were quantitative, or could be reproduced in an independent study; whereas Dr. Kenyon was not ready to pass judgment without further examination. Dr. Gibson echoed Dr. Rusyn's comments concerning the ambiguity of these studies and the lack of relevance to human exposures. DEQ-CFW 00000683 Dr. Starr requested that a meeting between him and Drs. Lau, Fenton, Kenyon, Rusyn, Spoo, and Kennedy, regarding the LOAEL and differing endpoints be set up prior to the next SAB meeting. Dr. Kenyon agreed intimating that key questions should be itemized prior to the meeting. PFOA tvz— Dr. Starr Dr. Starr reported that Dr. Clewell used the half-life of 3.8 years as reported in Olsen et.al. (2007). There is no half-life parameter in his PBPK model; instead there are binding constants for a transporter protein in the blood (Vmax and km). What Dr. Clewell did was to adjust the km in the human model to yield an equivalent VmaX over km effective rate constant that was proportional to the reciprocal of the human half- life. A half-life of 2.5 years (Bartell et.al. 2010) would make the NCSAB estimate less conservative. In other words a shorter half-life leads to lower serum levels at the same intake rate, so the NCSAB assessment with the longer half-life is conservative. Vote on publishing draft risk assessment for PFOA on the website for public comment Dr. Starr moved to publish the draft risk assessment for PFOA on the website (http://daci.state.nc.us/toxics/risk/sab/ra/). The proposed Maximum Allowable Level (MAC) for PFOA in groundwater ranges from 0.9 — 1.6 pg/L (ppbv). All members agreed. Dr. Kenyon asked that the language regarding chronic and subchronic studies in the Uncertainty factors table be clarified prior to posting. The public comment period will be for 30 days after posting. Public Forum Connie Brower, Division of Water Quality (DWQ) thanked the NCSAB for their efforts regarding research and development of the MAC for PFOA for the DWQ. Other Business The minutes from the 1491h meeting were approved as amended. Agenda for the Next NCSAB Meeting Review of Zhao et.al. — Dr. Spoo Report of alternative POD with Drs. Lau and Fenton — Dr. Starr Discussion of impact of Fenton/Lau teleconference on draft risk assessment The next meeting of the NCSAB will be held at 2:OOPM on WEDNESDAY, May 26, 2010 via teleconference. The call -in number is (919) 733-2441. The meeting was adjourned at 3:23PM. Respectfully submitted, Reginald C. Jordan, Ph.D., CIH Liaison, Science Advisory Board These minutes were accepted as written at the 151 sr SAB meeting, May 26, 2010. References Macon et. al. 2010. Poster Board 435. Developmental Exposure of CD-1 Mice to PFOA Identifies the Mammary Gland as a Low Dose Target Tissue. M. B. Macon; J. P. Stanko; S. E. Fenton presented at the Society of Toxicology Annual Meeting, March 2010. DEQ-CFW 00000684 Zhao et.al. 2010. Perfluorooctanoic acid effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57131/6 mice. ToxSci Advance Access published January 29, 2010 Olsen et.al. 2007. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ. Health Perspect., 115(9), 1298-1305. Bartell et.al. 2010. Rate of Decline in Serum PFOA Concentrations after Granular Activated Carbon Filtration at Two Public Water Systems in Ohio and West Virginia. Environ Health Perspect. 2010 Feb;118(2):222-8. Lau et.al. 2006. Effects of perfuorooctanoic acid exposure during pregnancy in the mouse. Toxicol Sci, 90(2), 510-518. Fenton et.al. 2009. Analysis of PFOA in Dosed CD-1 Mice Part 2: Disposition of PFOA in tissues and fluids from pregnant and lactating mice and their pups. Reprod Toxicol 27:365-372. Recent Advances in Perfluoroalkyl Acid Research doi:10.1016/j.reprotox.2009.02.012 Hines et.al. 2009. Phenotypic Dichotomy Following Developmental Exposure to Perfluorooctanoic Acid (PFOA) in Female CD-1 Mice: Low Doses Induce Elevated Serum Leptin and Insulin, and Overweight in Mid-life. Mol Cell Endocrinol 304:97-105. doi:10.1016/j.mce.2009.02.021 Hines et.al., 2009b. Testing the uterotrophic activity of perfluorooctanoic acid (PFOA) in the immature CD-1 mouse, Toxicologist 108 (2009), p. 297. 4 DEQ-CFW 00000685 P17—Perfluorinated Compounds in the Ohio River Basin Shoji F. Nakayama,' Erich Emery,2 Marc A. Mills,' and John Spaeth 'U.S. Environmental Protection Agency, National Risk Management Research Laboratory, Cincinnati, OH; 2Ohio River Valley Water Sanitation Commission, Cincinnati, OH Contaminants of emerging concern (CECs) in waterways include pharmaceuticals and personal care products (PPCPs), akylphenols, endocrine disrupting chemicals (EDCs) and perfluorinated alkyl compounds (PFCs). Their distributions and persistence in the aquatic environment remain poorly defined and public awareness and concern about these materials is increasing. Among these compounds, the PFCs have been studied in a small number of U.S. watersheds, with data describing their longitudinal occurrence and concentration In large river systems still being very scarce. Because the Ohio River and its tributaries provide drinking water, irrigation, and recreation for 25 million people living in this basin, it is essential to determine the occurrence and concentration of the various PFCs in the surface water resources of this region. To meet this need, in the fall of 2009, the Ohio River Valley Water Sanitation Commission (ORSANCO) collaborated with U.S EPA to collect single grab samples from 22 locations on the Ohio River and some selected tributaries. The primary focus of this study was to document the occurrence and concentrations of CECs, including PFCs. Resulting data for the PFCs will be presented. P18—Adjuvancy and Immunosuppression: Mechanisms of Immunomodulation Following Dermal Exposure to PFOA in Mice Jennifer Franko, Laurel G. Jackson, B. J. Meade, H. Fred Frasch, Antonia M. Calafat, Kayoko Kato, and Stacey E. Anderson National Institute for Occupational Safety and Health, Morgantown, WV, and CDC, Atlanta, GA The majority of investigations into the immunotoxic effects of perfluoroalkyl acids have focused on immunosuppression following the oral route of exposure. The potential for dermal exposure, however, also exists during the manufacturing process of products, reformulations and in use of end products such as fire -retardants. Serum perfluorooctanoic acid (PFOA) levels were analyzed following four days of dermal exposure in Balb/c mice (total administered dose 100 mg/kg PFOA) and were found to be similar (188+/-16 pg/ml) to those documented after oral exposure to similar doses of PFOA (168+/-8 pg/ml). In addition, preliminary data from skin penetration studies also suggest that there are similar amounts of PFOA penetration and absorption between human and mouse skin further supporting this as a valid route of human exposure. Recent immunotoxicological studies have demonstrated that oral dosing and dermal exposure (1-2%) result in qualitatively similar immunosuppressive effects including decreased spleen and thymus weight, increased liver weight, and a 62% decrease in the IgM response to SRBC when evaluated in a murine model. Additionally, we have shown that while not allergenic itself, dermal application of PFOA, at concentrations up to 1.5%, simultaneously with exposure to a respiratory allergen augments the allergic response to that allergen. Observed changes in mice include elevations in total and antigen -specific IgE and IgG1, increased airway hyperreactivity, and increased IL-4 and IL-5 production compared to mice exposed to allergen alone. This presentation will discuss the modulation of immune related markers following PFOA exposure, helping to explain the reciprocal relationship between the mechanisms governing immune suppression and augmentation of IgE-mediated hypersensitivity, as well as demonstrate absorption and penetration of PFOA through human and mouse skin. P19—Concentrations of Per -fluorinated Compounds in River Water in Tokyo Tetsuji Nishimura' and Toshinad Suzuki2 'Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan; 2Division of Water Quality, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan The presence of per -fluorinated compounds (PFCs) in the aquatic environment, as well as their toxicity and bioaccumulation potential, causes concern for the aquatic ecosystem and human health. In Tokyo, urban river water and ground water are used as drinking water source. First, the analytical method for PFCs in water samples by solid -phase extraction (SPE) and liquid chromatography -tandem mass spectrometry (LC-MS/MS) was confirmed in order to clarify the presence of PFCs in the river water in Tokyo. Per-fluorocarboxylic acids (PFCAs) with carbon chain lengths from five to fourteen carbons and 43 DEQ-CFW 00000686 per-fluorosulfonic acids (PFCSs) with carbon chain lengths from four to ten carbons were completely separated by ODS analytical column with ammonium acetate-acetonitrile as mobile phase. The tandem mass spectrometry condition was operated under multiple reaction monitoring (MRM) mode, and the parameters were optimized for transmission of the [M-K]- or [M-H]-ions. The limits of qualification on this system was 0.05 to 0.2 micro-g/L. The effective reduction of PFCs contamination in the laboratory was done by removing Teflon products, washing SIDE cartridge and glass ware with methanol, and using PFCs free water. SPE cartridges prepared by polymer -based sorbent were suitable for the extraction of PFCs with shorter chain lengths in water samples rather than that prepared by silica gel -based sorbent. The recoveries of PFCs from several water samples by the present method ranged from76 to 103%, except for less than 50% of PFCAs which have carbon chain lengths shorter than six carbons. The monitoring of PFCs in river water was performed at Tama River and Naka River basins in Tokyo. These rivers are suitable to observe pollution from human activity. Because, the six sewage treatment plants exist around the Tama River basin, and serve to about 2.2 million populations. PFCs were detected from every water samples receiving the load of the drainage from swage treatment plants. The average of the total concentrations was 33.4 ng/L for PFCAs and 75.2 ng/L for PFCSs in 2008. The high abundant compounds in PFCAs were perfluoronanoic acid (PFNA, 42%), perfluorooctanoic acid (PFOA, 32%), and perfluorohexanoic acid (PFHxA, 14%). The high abundant compounds in PFCSs were perfluorooctan sulfonic acid (PFOS, 80%), perfluorohexane sulfonic acid (PFHxS, 16%), and pefluorobutane sulfonic acid (PFBS, 3%). PFHxA was detected in samples collected since May, 2008. It might be due to the use of the replacement of PFDA. A little amount of PFOA and PFOS existed in suspended solid in water samples. As for Naka River basin, the frequency and the ratio of PFCs were similar to those of Tama River basin. The average of total amount of PFCAs and PFCSs in the downstream sites in Tama River basin was estimated 80 g/day and 90 g/day, respectively. The discharge of PFCs from six swage treatment plants was estimated 59 g/day and 67 g/day, respectively. These results indicated that a major pollution source of PFCs for the river water was the effluent of swage treatment plants. 1320—The Toxicokinetics of Various Perfluorinated Alkyl Chemicals in the Harlan Spraque-Dawley Rat Chad R. Blystone, Veronica G. Robinson, Cynthia S. Smith, Ron L. Melnick, Kris A. Thayer, and Michael J. De Vito National Toxicology Program, NIEHS, Research Triangle Park, NC The toxicokinetic properties of perfluorinated alkyl chemicals vary greatly due to differences in elimination rates across species, sexes, and chain length, which makes comparative toxicity and risk assessments across the class difficult when using external dose metrics. The National Toxicology Program is undertaking a toxicity evaluation of the perfluorinated chemicals class and conducted toxicokinetic studies of perfluorobutane sulfonate potassium salt (PFBS), perfluorohexane sulfonate potassium salt (PFHxS), perfluorooctane sulfonate (PFOS), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), and perfluorodecanoic acid (PFDA) in male and female Harlan Sprague Dawley Rats (8-9 wks old) to characterize the kinetics in this animal model. A single IV or oral dose (three concentrations) was administered in deionized water with 2% Tween 80. At varying time points plasma concentrations (n = 3/time point) were determined by chromatography with mass spectroscopy (LC-MS/MS). Data sets were evaluated using one or two compartmental models (WinNonlin). As expected, the half life and elimination rates was shorter and faster respectively in female rats for PFOA. PFHxA, PFBS, and PFHxS also displayed a similar sex difference pattern while PFOS and PFDA did not. In both sexes, the shorter chained PFBS and PFHxS were eliminated quickly (hours) while PFOS and PFDA had much longer (weeks) half lives. In female rats, PFHxA displayed biphasic elimination. The bioavailability for these chemicals was generally around 100%. These data will provide guidance for dose selection in the NTP class toxicity evaluation and assist the risk assessment for this chemical class. ME DEQ-CFW 00000687 P21—Assessment, Remediation and Risk Assessment of Perfluorinated Chemicals at 2 Former Fire Training Areas Ian Chatwell Transport Canada, Vancouver, British Columbia, Canada Transport Canada historically operated two former fire training areas (FTAs) in central British Columbia, Canada. FTA 1 and 2 were used for fire-fighter training between 1972 and 1992. Each FTA formerly included an aircraft mockup (comprised of culvert sections), a fuelling station (above ground fuel storage and pump) and fuel distribution lines. The fire training exercises consisted of flooding the aircraft mockups with fuel, igniting the fuel and conducting fire training exercises using fire suppression products such as Aqueous Film Forming Foam (AFFF), Super K and Purple K. It has been estimated that at least 2,000 litres (L) and 2,700 L of AFFF were consumed annually at FTA 1 and FTA 2, respectively. According to various Material Safety Data Sheets (MSDS), AFFF products are reported to contain a variety of substances including water (65-85%), urea (3-7%), diethylene glycol butyl ether (10-20%), alkyl sulphate salts (1-5%), perfluoroalkyl sulfonate salts (0.1-1%), triethanolamine (0.1- 1 %), fluoroalkylamides (2%) and residual organic fluorochemicals (<1 %). Assuming that at least 1 % of the applied AFFF consists of PFCs (Hekster et al., 2002), it is anticipated that at least 470 L of PFCs may have been deposited at the FTAs over the periods of the fire training activities. Environmental investigations of perfluorinated chemicals (PFCs) at the FTAs commenced in 2006. Between November 2006 and July 2009, samples of soil, groundwater, soil invertebrate and plant tissue, and small mammal tissue were collected from the Site and analyzed for PFCs. In addition to characterizing and delineating PFCs contamination, site -specific risk based soil and groundwater remedial targets were derived for PFOS and other PFCs. A soil leaching study was completed in 2009. A Vacuum Enhanced Multi -phase Extraction System has been operating at the site since 2005 to remove free -phase hydrocarbons, the effectiveness of the system to remediate PFCs has been evaluated. The poster would summarize findings of our work. P22—Comparative Pharmacokinetics of Perfluorohexanesulfonate (PFHxS) in Rats and Monkeys Maria Sundstrom,' Shu-Ching Chang,2 David J. Ehresman,2 Patricia E. Noker,3 Geary W. Olsen,2 Gregory S. Gorman,' Jill A. Hart,2 Trina N. John,4 Ake Bergman,' and John L. Butenhoff 'Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden; 23M Company, St. Paul, MN; 3Southern Research Institute, Birmingham, AL; 4Pace Analytical Services, Minneapolis, MN Perfluorohexanesulfonate (PFHxS) has been found in biological samples from wildlife and humans. The geometric mean half-life of serum elimination of PFHxS in humans has been estimated to be 7.3 years (95% Cl 5.8-9.2 years). A series of studies was undertaken to establish pharmacokinetic parameters in non -human species. Male (M) and female (F) monkeys were given a single intravenous (IV) dose of K+PFHxS and serum and urine PFHxS concentrations were followed for 171 d. M and F rats were given single oral doses of 1, 10, or 100 mg/kg K+PFHxS and urine and feces were collected over 96 h and serum and liver collected at 96 h. Jugular-cannulated M and F rats were given either IV or oral single 10 mg/kg doses of K+PFHxS and serum concentrations of PFHxS were followed for 24 h. M and F rats were given a single IV dose of 10 mg/kg, and serum, feces, and urine were collected weekly for 10 weeks. All PFHxS analyses utilized LC-MS\MS methods. Pharmacokinetic parameters were determined by WinNonlin® software. Volumes of distribution indicated predominant extracellular distribution. Mean serum elimination half-lives were 141 and 87 d for M and F monkeys and ca. 30 and 1.5 d for M and F rats. 45 DEQ-CFW 00000688 P23—Investigation of Waste Incineration of Fluorotelomer-Based Polymers and Fluoropolymers as a Potential Source of PFOA in the Environment P. H. Taylor,' T. Yamada,' R. C. Striebich,' J. L. Graham,' and R. J. Giraud2 'University of Dayton Research Institute, Environmental Engineering Group, Dayton, OH; 2DuPont Engineering Research and Technology, Wilmington, DE In light of the widespread presence of perfluorooctanoic acid (PFOA) in the environment, two comprehensive laboratory -scale studies have developed data requested by U.S. EPA to determine whether municipal and/or medical waste incineration of either commercial fluorotelomer-based polymers or commercial fluoropolymers at end of life is a potential source of PFOA that may contribute to environmental and human exposures. Each study was divided into two phases (I and 11) and conducted in accordance with U.S. EPA Good Laboratory Practices (GLPs) as described in the quality assurance project plan (QAPP) for each phase. Phase I testing (in common between the two studies) met its Data Quality Objective (DQO); the resulting PFOA transport efficiency across the thermal reactor system to be used in Phase 11 was greater than 90%. Phase 11 combustion testing of the test substance composites for both studies in this thermal reactor system met their respective DQOs and yielded results demonstrating that waste incineration of neither fluorotelomer-based polymers nor fluoropolymers emit detectable levels of PFOA under conditions representative of typical municipal waste combustor operations in the U.S. Therefore, waste incineration of these polymers is not expected to be a source of PFOA in the environment. P24—Comparative Pharmacokinetics of Perfluorooctanesulfonate (PFOS) in Rats, Mice, and Monkeys Shu-Ching Chang,' David J. Ehresman,' Patricia E. Noker,2 Gregory S. Gorman,2 Jill A. Hart,' Trina N. John,3 Alan Eveland,3 Jeremy ZitzoW,3 and John L. Butenhoff' '3M Company, St. Paul, MN; 2Southern Research Institute, Birmingham, AL; 3Pace Analytical Services, Minneapolis, MN Perfluorooctanesulfonate (PFOS) has been found in biological samples in wildlife and humans. The geometric mean half-life of serum elimination of PFOS in humans has been estimated to be 4.8 years (95% Cl 4.0 — 5.8 years). A series of studies was undertaken to establish pharmacokinetic parameters in non -human species. Jugular-cannulated male (M) and female (F) rats were given either IV or oral single 2 mg/kg doses of K+PFOS and serum concentrations of PFOS were followed for 24 h. M and F rats were given single oral doses of 2 or 15 mg/kg K+PFOS, and concentrations of PFOS in serum, urine, and feces were followed for 10 weeks. M and F rats were given daily oral doses of 1 mg/kg/d K+PFOS for 28 consecutive days with an additional 10-week recovery period. Serum was collected on a weekly basis for measurement of serum PFOS concentrations throughout the study. Overnight urine and feces were collected once a week during the recovery period for analysis of PFOS concentrations. M and F mice were given a single oral dose of 1 or 20 mg/kg K+PFOS, and concentrations of PFOS in serum, urine, and feces were followed for 10 weeks. M and F monkeys were given a single IV dose of K+PFOS (2 mg/kg) and serum and urine PFOS concentrations were followed for 171 days. All PFOS analyses utilized LC- MS/MS methods. Pharmacokinetic parameters were determined by WinNonlins software. Volumes of distribution indicated predominant extracellular distribution. Mean serum elimination half-lives for M and F respectively, were 43 and 60 days in rats; 40 and 34 days in mice; and 131 and 110 days in monkeys. P25—Environmental Releases of Perfluorochemicals (PFCs) from Two Landfills in Minnesota Fardin Oliaei This study examined 12 PFC compounds in leachates, gas condensate, soils, and groundwater at two landfills in the Twin Cities Metro area of Minnesota. One landfill, the Pine Bend Landfill (PBLF), received wastewater treatment plant sludges from a 3M PFC production facility in Minnesota. The other landfill, the Washington County Landfill, received past PFC wastes from the 3M PFC production facility. This study tested PFCs in gas condensate, leachate, and groundwater from the Pine Bend Landfill. The Pine Bend Landfill burns landfill gases, with gas condensate generated upon combustion of collected M. DEQ-CFW 00000689 landfill gases. We found PFOA in gas condensate at 83.8 ppb, PFOS at 29.9 ppb, and PFHxA at 37.9 ppb, with other PFCs at lower concentrations. We found that gas condensate contained higher levels of PFCs than PFCs in the leachate generated at the landfill. Groundwater tested at this landfill shows that PFCs have migrated from wastes to groundwater. The Washington County Closed Landfill (WCLF) received PFC production wastes. The WCLF, which is unlined, used a spray nozzle stripper system to volatilize VOC contaminated groundwater under the site into the atmosphere for about 25 years. We found that groundwater under the landfill contained elevated levels of PFCs, and also found that the spray water contained elevated levels of PFCs. The spray water may produce aerosols. PFCs contained in aerosols, or PFCs subject to volatilization, may pose a source of air transport of PFCs to local areas. The extent of this transport, if any, is unknown. The presence of PFCs in gas condensates at the PBLF suggests that exhaust gas emissions from this landfill may also contain PFCs. Other landfills, such as municipal landfills, receive consumer products that contain lower levels of PFC residuals. Studies have shown that leachates and groundwater proximate to some of these landfills contain PFCs. Although most of these landfills do not receive PFC production wastes or PFC containing sludges, off gases from these landfills could contain PFCs, although likely at significantly lower concentrations than the PBLF. However, landfills could collectively comprise a source of PFCs emitted into the atmosphere. P26—Comparative Pharmacokinetics of Perfluorononanoic acid in Rats and Mice K. Tatum,' K. Das,2 R. Zehr,2 M.J. Strynar,3 A.B. Lindstrom,3 A. Delinsky,3 J. Wambaugh,4 and C. Lau2 Curriculum in Toxicology, University of North Carolina , Chapel Hill, NC, 2Reproductive Toxicology Division, US EPA, RTP, NC, 3Human Exposure and Atmospheric Sciences Division, US EPA, RTP, NC, 4National Center for Computational Toxicology, US EPA, RTP, NC Perfluorononanoic acid (PFNA) is a perfluoroalkyl acid (PFAA) that has been detected at low concentrations in the environment. The potential human risks associated with these low concentrations and their potential toxicity has not been well defined and is currently under investigation. Previous studies have examined the pharmacokinetics (PK) of PFNA in rats and the sex -related differences that occur with this particular animal model. This study evaluated and compared the PK properties of PFNA in two laboratory animal species, the rat and mouse and highlighted any species differences. Male and female mice (4/sex/group) received a single oral administration of PFNA at 1 mg/kg or 10 mg/kg. Four animals were killed from each group at 1, 4, 7, 11, 16, 21, 28, 35, 42, and 50 days following treatment. Plasma was collected from each animal via decapitation as well as the liver and kidney. Male and female rats (3/sex/group) received a single oral treatment of PFNA via oral gavage at concentrations 1, 3, or 10 mg/kg. Plasma was collected from each animal via tail bleed at similar time intervals as the mouse. Terminal sacrifices for each group occurred 50 days after treatment; plasma liver and kidney samples were evaluated for PFNA concentrations. Controls in all groups received water alone. Concentrations of PFNA were determined in serum, liver and kidney of both species utilizing HPLC-MS- MS. In addition, serum concentrations vs. time were then analyzed by compartmental pharmacokinetic methods. Both species exhibited a gender difference in the elimination of PFNA, but rats showed a significant difference among males and females. In the rat, the rate constant for elimination was significantly faster in female rats compared to male rats (Kein = 0.010/h for females and 0.0014/h for males), which resulted in an estimated serum half-lives that was considerably different between the two genders ( t112 = 30.7 and 1.8 days for males and females, respectively). In the mouse, the rate constant for elimination was slightly faster in females than males (Ke,;m = 0.0011/h for females and 0.0007/h for males), resulting in a serum half-life relatively comparable between the two sexes (t,, = 40.7 days for females and 64.4 days for males). Correspondingly, the appearance of PFNA in the liver was faster, and the chemical reached higher levels in the male mice than in the females. These data thus suggest that (1) PFNA is more persistent than the lower carbon chain PFAAs, such as PFOA and PFBA in these rodents models; (2) PFNA is more persistent in the mouse than in the rat; (3) there is a major sex difference in the serum elimination of PFNA in the rat, but the differences are much smaller in the mouse; and (4) there is a significantly higher accumulation of PFNA in the liver of male mice than that in the females. This abstract does not necessarily reflect U.S. EPA policy. 47 DEQ-CFW 00000690 P27—Discovery of PFC Contamination in Fish near a PFC Manufacturing Plant in Minnesota Fardin Oliaei This study was the first study in Minnesota to examine PFC contamination in fish downstream of a perfluorochemical production facility (3M Cottage Grove plant). This fish study was part of a larger study (Investigation of Perfluorochemical (PFC) Contamination in Minnesota -Phase 1), conducted by current and former Minnesota Pollution Control Agency (MPCA) staff, that also examined PFC contamination at other sites and media in Minnesota. PFC analysis in Mississippi River fish downstream of the PFC production facility was significantly expanded upon in subsequent work conducted by the MPCA in 2006- 2008. We analyzed fish fillets from 45 individual fish collected from two areas (pools 2 and 4) in the Mississippi River downstream of the PFC production facility in October 2005. High levels of PFOS were found in all fish tested, with 43 of 45 fish (fillets) exceeding a Minnesota Department of Health guideline, established in 2006 after this study, that triggered a fish consumption advisory at 40 ng/g (ppb). We found considerable variability in PFOS concentrations within any fish species. PFOS levels did not follow the typical pattern of bioaccumulation that often increases with age, weight, and trophic level. PFOS in this study, and subsequent MPCA studies, show that certain species (Smailmouth Bass, Bluegill, White Bass) typically contain the highest concentrations of PFCs. Species specific concentration factors may account for large differences in PFOS concentrations for different species residing in the same areas of water. The chemical and physical characteristics of PFCs, as surfactants, may also affect exposure mechanisms and bioconcentration/bioaccumulation factors. This study also measured PFCs in fish blood from the 21 individual fish collected in Mississippi River pool 2. Concentrations of PFOS in fish blood were high for all fish, ranging from 136 ppb in a Walleye to 29600 ppb in a White Bass. Based on our review of the literature we believe that the 29600 ppb PFOS in blood of the White Bass is the highest PFOS concentration in any animal tissue or animal blood tested worldwide. P28—The Effect of Colesevelam Hydrochloride on the Elimination of Potassium Perfluorooctanoate (PFOA) from Serum in Male and Female Cynomolgus Monkeys David J. Ehresman,1 Patrick E. Noker, 2 Larry R. Zobel,' Geary W. Olsen,1 Shu-Ching Chang,1 and John L. Butenhoffl 13M Company, St. Paul, MN; 2Southern Research Institute, Birmingham, AL Perfluorooctanoate (PFOA) is widely distributed in humans and wildlife. In retired workers with occupational exposure to PFOA, the geometric mean serum PFOA elimination half-life was reported to be 3.5 yrs. Previously, dietary administration of cholestyramine, a bile acid and lipid binding polymer, was found to increase the fecal elimination of 14C approximately 10-fold in rats after a single IV dose of 14C- labeled PFOA. The purpose of this study was to evaluate whether colesevelam hydrochloride (colesevelam HCI), another lipid -lowering polymer in clinical use that impedes bile acid and cholesterol absorption in the intestine, can affect the elimination of PFOA from serum in cynomolgus monkeys. In this study, each monkey served as its own control in that the rate of serum elimination of PFOA during periods in which colesevelam HCL was administered was compared to the rate during periods in which a placebo was given. Monkeys were assigned into two groups which received either placebo or colesevelam HCL on separate schedules. On study day (SD) 0, monkeys (N=3/sex/group, individually - housed, age 2->5 yrs old) received a single intravenous dose of K+PFOA (10 mg/kg) in the cephalic vein. On SD 28-55, daily oral doses of colesevelam HCI (250 mg/kg/d) were given Group 1 monkeys while Group 2 monkeys received colesevelam HCI on SD 56-83. On SD 21-27 and 56-83, daily oral doses of placebo (water) were given to Group 1 monkeys while Group 2 monkeys received placebo on SD 21-55. Serum samples were collected and analyzed for PFOA concentrations using LC/MS-MS from each monkey prior to dosing (0 hr), on SD 0 (0.5 h post IV dose), 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84. All monkeys survived until the end of the study. There were no clinically abnormal observations noted, DEQ-CFW 00000691 and body weights were similar between dose groups in each sex during the study. Colesevelam HCL treatment did not alter the serum PFOA elimination rate when compared with placebo treatment. In either male (M) or female (F) monkeys, there was no apparent difference in mean serum PFOA levels between Group 1 (given colesevelam HCI on SD 28-55) and Group 2 (given colesevelam HCI on SD 56-83). Pharmacokinetic parameters indicated similar mean overall serum half-life (T1/2) and AUC values of PFOA in M monkeys in Group 1 (T1,2 =18.8 days, AUC =1965 hr•pg/mL) and Group 2 (T1/2 =17.0 days, AUC = 1716 hr•pg/mL); as well as in F monkeys in Group 1 (T1/2 =26.3 days, AUC = 2869 hr•pg/mL) and Group 2 (T1/2 = 28.4 days, AUC = 2192 hr•pg/mL). Therefore, administration of colesevelam HCI had no therapeutically significant impact on serum PFOA levels, serum PFOA half-life, or serum PFOA AUC levels within the limits of the study design. P29—PFCs in Indoor Office Air: Concentrations and Contribution to Exposure Alicia J Fraser,' Thomas F Webster,' Deborah J Watkins,' Jessica W Nelson,' Heather M Stapleton, z Mahiba Shoeib,3 Veronica M Vieira,' and Michael D McClean' 'Boston University School of Public Health, Boston MA; 2Duke University, Nicholas School of the Environment, Durham NC; 3Environment Canada, Toronto, ON Introduction: Certain polyfluorinated compounds (PFCs) are persistent, bioaccumulative and toxic compounds found ubiquitously in the indoor and outdoor environments and in people. They are present in air, dust, food, water and consumer products, yet little is known about the contribution of different exposure pathways and microenvironments to human body burdens. Furthermore, even less is known about exposure to precursor compounds (fluorotelomer alcohols [FTOHs] and sulfonamides [FOSAs and FOSEs]) and their contribution to body burdens. The primary goal of this research was to investigate the role of indoor office air on exposure to PFCs by characterizing levels of PFC precursor compounds in indoor office air and examining their association with PFC serum concentrations, including perfluorooctanoic acid (PFOA) and perfluorosulfonic acid (PFOS), in office workers. Materials and Methods: Week-long, active air sampling was conducted during the winter of 2009 in 31 offices located throughout seven buildings in Boston, MA. Air samples were analyzed for FTOHs, FOSAs, and FOSEs. Serum was collected from each office worker at the end of the sampling week and analyzed for eight PFCs including PFOA and PFOS. Results and Discussion: FTOHs in air, particularly 8:2 FTOH (GM = 9,925 pg/m3), were found in the highest concentrations and were found to vary significantly by building with the highest levels observed in the only newly constructed and furnished office building. Serum PFOA varied by office building in the same manner as FTOHs in air. PFOA in serum was significantly correlated with 6:2 FTOH (1=0.43), 8:2 FTOH (r=0.60), and 10:2 FTOH (r=0.62) in air. Using principle components analysis to investigate the effect of FTOHs, collectively, on PFOA in serum, we found that FTOH concentrations were a significant predictor of PFOA in serum (p < 0.001) and explained approximately 36% of the variation in serum PFOA concentrations. PFOS in serum was also found to be highest in workers of the newly constructed building, but was not associated with levels of FOSAs/FOSEs in air. Concentrations of FTOHs in office air are a significant predictor of PFOA in the serum of office workers. Variation in PFC air concentrations by building is likely due to off -gassing from new carpeting, furniture and/or paint. Acknowledgements: We would like to thank Antonia M Calafat and Kayoko Kato of the Centers for Disease Control and Prevention in Atlanta, GA for their analysis of PFCs in the serum samples for this study. P30—Development of Rat Gestation and Lactation PBPK Models for PFOA/PFOS Anne E. Loccisano, Melvin E. Andersen, and Harvey J. Clewell 111 The Hamner Institutes for Health Sciences, Research Triangle Park, NC Developmental toxicity studies in rodents show that fetuses/neonates can be exposed to both PFOA and PFOS in utero and via lactation and have raised concern about potential developmental effects of PFOA and PFOS in human populations. We have developed PBPK models for these compounds in the rat to help define a relationship between external dose, internal tissue concentrations, and observed adverse effects, and to understand how the physiological changes that occur during gestation and lactation affect DEQ-CFW 00000692 the tissue distribution of PFOA and PFOS in the mother, fetus, and neonate,. The gestation and lactation models expand upon a PBPK model for PFOA and PFOS in the adult female rat. In order to properly describe available data, the model required renal resorption, saturable binding in liver, and a varying free fraction of chemical in plasma. The model was used to simulate time course concentration data in maternal, fetal, and neonatal rat tissues during gestation and lactation from several available studies. The same model structure and same set of chemical parameters used in the adult rat model allowed for simulation of the tissue concentrations in the pregnant and lactating dam, indicating that pharmacokinetics in these life stages are similar to those in the adult. Simple diffusion was sufficient to describe placental and milk transfer of both chemicals. The fetal parameters were the same as those used in the dam, with the exception of saturable binding in liver. This was not required for accurately simulating PFAA concentrations in fetal liver most likely because the fetal liver does not yet have the capacity to sequester chemical as the dam does. The gestation model provided the initial values for tissue levels of chemical for simulating lactation exposure. In the neonatal rat for PFOS, the pup parameters were the same as used for the dam. However, for PFOA, the adult male rat parameters were used in the pups because under 5 weeks of age, both male and female pups have a slow clearance of the chemical like the adult male. The rat model has helped in identifying research needs for a more detailed model: characterization of transporter properties for renal resorption and gestational changes in serum protein binding. These models will be extrapolated to humans to help determine how the changing physiology and growth during these life stages may affect PK and tissue disposition of PFAAs. P31—Concentration of Perfluorinated Organic Compounds of Tap Water in Japan Norimitsu Saito,' Kazuaki Sasaki,' Kaori Yaegashi,' Syuhei Tanaka,' Shigeo Fujii,' Naoto Shimizu,3 and Shuji Tsuda4 'RIEP of Iwate Prefecture, 2Kyoto University, 3Agilent Technologies, and 4lwate University, Japan Introduction We have reported that both of the concentrations of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) in all 79 Japanese rivers were more than 0.1 ng/L and in serum for 90 Japanese people were more than 0.1 ":g/L, respectively. We have also reported good correlations in PFOS and PFOA concentrations between tap water and serum. The major source of drinking water is regarded as tap water. Therefore, we investigated the concentration of PFCs including PFOA and PFOS in Japanese tap water for 142 locations with simultaneous PFCs analyses. The detection rate for the perfluorocarboxylates (C6 — C11) was more than 50%, PFOA showed the highest rate of 93.7%, perfluorononanoate was 88.8%, perfluoroheptanoate was 83.1 % and perfluorodecanoate was 81.0%. Only four compounds were exceeded 0.1 ng/kg in geometric means in tap water, that is, PFOA was 0.57 (max:35.1) ng/kg, perfluorononanoate was 0.26 (max:34.1) ng/kg, perfluoroheptanoate was 0.13 (max:9.19) ng/kg and PFOS was 0.29 (max:24.8) ng/kg, respectively. As the regional difference of PFCs concentration in geometric means, the highest area was Kinki followed by Kanto and Chubu area in this order, except for perlluorobutanesulfonate which was highest in Kanto. Because the PFCs concentrations in the Hokkaido-Tohoku area were lower than other areas, it seems the PFCs pollution of south area from Kanto is more serious. The highest areas for each PFCs are: PFOA in Kobe was 35.1 ng/kg, perfluoroheptanoate in Sabae was 9.19 ng/kg and perfluorodecanoate in Naha was 5.81 ng/kg. We have already obtained good correlations in PFC concentrations between tap water and river water in general. Thus, it seems that the PFCs concentrations in tap water in those areas are affected by the local industries, although the direct relation between tap water and river water in those areas has not been compared. 1332—Effects of PFCs on Gene Expression of the H411E Rat Hepatoma Cell Line Jonathan Naile,1 Steve Wiseman,' Paul D. Jones,' and John P. Giesy1,2,3 'Department of Biomedical Veterinary Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Zoology Department, Center for Integrative Toxicology, Michigan State University, East Lansing, MI; 3Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, SAR China DEQ-CFW 00000693 Perfluorinated compounds (PFCs) have been released into the environment during manufacturing and use as wetting agents, lubricants, stain resistant treatments, and foam fire extinguishers, and are now ubiquitous in the environment in a wide range of biotic and abiotic matrices. Perfluorooctanesulfonate (PFOS) is the terminal degradation product of many commercially used perfluorinated compounds and most of the toxicity testing to date has focused on its potential biological effects. While PFOS has been extensively studied other PFCs, including replacement chemicals such as perfluorobutanesulfonate (PFBS) and perfluorobutyrate (PFBA), have not been well characterized. Despite the relative lack of data available on these other PFCs; it has been assumed that they will cause similar or lesser effects than PFOS. This study compared the effects of 10 PFCs routinely found in the environment on mRNA abundance of 7 genes related to processes known to be affected by PFOS, such as fatty acid and cholesterol synthesis, and thyroid development. Rat H411E hepatoma cells were exposed to 0.1, 1, 10 or 100 pM PFCs for 72 h and changes in mRNA expression. Significant changes in mRNA expression were observed and not all PFCs caused the same effects on the genes studied, and these changes could not simply be attributed to chainlength or functional group. Furthermore, the effects caused by the shorter chain replacement chemicals differed significantly from those caused by PFOS or PFOA. These differences could mean that these replacement chemicals do not act through the same mechanisms as the more studied PFOS and PFOA. P33—Private Drinking Water Wells as a Source of Exposure to PFOA in Communities Surrounding a Fluoropolymer Production Facility Kate Hoffman,' Thomas F. Webster,' Scott M. Barte11,2 Marc G. Weisskopf,3 Tony Fletcher ,4 and Ver6nica M. Vieira I 'Department of Environmental Health, Boston University School of Public Health, Boston, MA; 2Program in Public Health, University of California, Irvine, CA; 3Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology, Harvard School of Public Health, Boston, MA; 4London School of Hygiene and Tropical Medicine, London, UK Background: The C8 Health Project was established in 2005 to collect data on perfluorooctanoic acid (PFOA, or C8) and human health in Ohio and West Virginia communities contaminated by a fluoropolymcr production facility. Objective: We assessed PFOA exposure via contaminated drinking water in a subset of C8 Health Project participants using private drinking water wells. Methods: Participants provided demographic information, and residential, occupational, and medical histories. Laboratory analyses were conducted to determine serum PFOA concentrations. PFOA monitoring data were collected from 2001 to 2005 in 62 private individual drinking water wells. We examined the relationship between drinking water and serum PFOA levels using robust regression methods. As a comparison, we used a first -order, single compartment pharmacokinetic model to estimate the serum to drinking water concentration ratio at steady-state. Results: The median serum PFOA concentration in 108 study participants using private wells was 75.7 pg/L, approximately 20 times greater than the US general population levels, but similar to local residents drinking public water. Each pg/L increase in drinking water PFOA is associated with an increase in serum concentrations of 141.5 pg/L (95% confidence interval 134.9-148.1) The serum to drinking water concentration ratio for the steady-state pharmacokinetic model i 114. i Conclusions: PFOA contaminated drinking water is a significant contributor to serum levels in this population. Regression methods and pharmacokinetic modeling produced similar estimates of the relationship. DEQ-CFW 00000694 P34—In Vitro Metabolism of 6-2fluorotelomer Alcohol in Rat, Mouse, and Human Hepatocytes SA Gannon,' DL Nabb,' TA Snow,' MP Mawn,' TL Serex,' RC Buck ,2 and SE Loveless' 'DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE; 2DuPont Chemical Solutions Enterprise, Wilmington, DE The identification of perfluorinated organic compounds in the environment has generated interest in understanding their biological and environmental fate. 6-2 fluorotelomer alcohol (6-2 FTOH, C6F13CH2CH2OH) is a raw material used in the manufacture of fluorotelomer-based products. This study investigated the in vitro metabolism of 6-2 FTOH and selected metabolites by rat, mouse, and human hepatocytes to determine metabolic pathways. Preliminary data showed 6-2 FTOH clearance in hepatocytes from rodent species is more rapid than in humans. Major metabolic pathways for 6-2 FTOH in hepatocytes from all three species included either the formation of glutathione, glucuronic acid, or sulfate conjugates of the parent. Formation of the glutathione conjugate was by far the most significant metabolic pathway in all three species. Another important metabolic pathway resulted in the formation of 6-2 aldehyde (AL) leading sequentially to 6-2 unsaturated aldehyde (UAL), 5-3 UAL, 5-3 unsaturated acid, and 5-3 acid (A). The 6-2 AL also led to production of 6-2 A, 5-3 beta-keto aldehyde, perfluorohexanoic acid, and perfluoropentanoic acid. The metabolic pathways were qualitatively similar between rat, mouse, and human hepatocytes, however, there were differences in metabolic flux leading to differences in the relative amounts of motabolites produced by each species. The observed pathways are similar to those observed following dosing with the structurally similar 8-2 FTOH (C6F15CH,CH,OH) and preliminary rate calculations indicate that 6-2 FTOH has a similar intrinsic clearance in hepatocytes. P35—Using On -Site Bioreactors to Determine the Fate of N-Ethyl Perfluorooctane Sulfonamidoethanol (N-EtFOSE) at a Wastewater Treatment Plant Kurt R. Rhoads, Katherine H. Rostkowski, Peter K. Kitanidis, and Craig S. Criddle Department of Civil and Environmental Engineering, Stanford University, Stanford, CA On -site rates for aerobic biotransformation of N-ethyl perfluorooctane sulfonamidoethanol (N-EtFOSE), a fluorinated repellent and precursor of perflurooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), were determined by continuously pumping mixed liquor from an aeration basin into two well - mixed acrylic bioreactors (4-liter) operated in parallel. Known masses of N-EtFOSE and bromide were continuously added to the reactors. Reactor effluents were then monitored for bromide, N-EtFOSE, and metabolites of N-EtFOSE. Of the six transformation products reported in batch studies, only N-ethyl perfluorooctane sulfonamido acetate (N-EtFOSAA) was detected in the effluents. Bromide addition to the reactors enabled rate estimates despite variations in flowrate. Pseudo -second order rate coefficients for the N-EtFOSE biotransformation to N-EtFOSAA, predicted using a dynamic model of the reactor system, were k = 2.6 and 2.7 L/g VSS day' for the two reactors, in agreement with values measured in batch incubations using undiluted activated sludge from the same source. The relatively slow rates of biotransformation indicate that the majority of N-EtFOSE entering a wastewater treatment plant will be volatilized or sorbed to waste solids and not be biotransformed to PFOS. P36—A Novel Fluorescence Model for Studying the Binding of Medium- to Long -Chain Perfluoroalkyl Acids to Human Serum Albumin Paul C. Hebert and Laura A. MacManus-Spencer Department of Chemistry, Union College, Schenectady, NY Perfluoroalkyl acids (PFAAs) are contaminants of emerging environmental concern recognized as both bioaccumulative and toxic. Binding to proteins is one proposed explanation for the preferential accumulation of PFAAs in the liver, the kidneys, and the blood. Characterization of PFAA binding to serum albumin — the most abundant protein in human blood — has been attempted with many techniques, though results vary widely. Recent studies have demonstrated the use of fluorescence spectroscopy to monitor albumin's tryptophan emission for analyses of PFC-albumin interactions, though without thoughtfully interpreting the results. To improve the fluorescence method, we have developed a novel 52 DEQ-CFW 00000695 model for measuring the strength of PFAA binding to human serum albumin (HSA) using changes in the protein's native fluorescence resulting from conformational changes in the protein. The model has been used to qualitatively and quantitatively characterize the binding of several medium- and long -chain PFAAs to HSA. Results indicate at least 2-3 PFAAs bind to each protein with affinity on the order of 104 M_1. Binding strengths demonstrate dependence upon perfluorocarbon chain length, ionic head group, and protein concentration. The model is not valid for the binding of short -chain PFAAs to HSA. Results suggest short -chain PFAAs associate with HSA differently than medium- and long -chain PFAAs, such that they fail to promote the same conformational changes in the protein's tertiary structure. P37—Aerobic Soil Biotransformation of Fluorotelomer Alcohols N. Wang,' J. Liu,2 R.C. Buck,' Patrick W Folsom,' L.M. Sulecki,' Barry Wo/stenholme,' P.K. Panciroli,' and C.A. Bellin' 1E.1. du Pont De Nemours & Co., Inc, Newark, DE; 2Chesapeake Biological Laboratory, University of Maryland Center for Environmental Science, Solomons, MD Fluorotelomer alcohols (FTOHs, F(CF2)nCH2CH2OH,) are a raw material used in the manufacture of fluorotelomer-based products. 8:2 FTOH (C$F17CH2CH2OH) biotransformation has been extensively studied in activated sludge, soils, sediments and landfills. A shorter chain length homolog, 6:2 FTOH (C6F13CH2CH2OH) and a longer chain 10:2 FTOH are also raw materials used to manufacture fluorotelomer-based products. The similarities and differences of 6:2 FTOH, 8:2 FTOH and 10:2 FTOH aerobic biodegradation pathways in closed and flow -through test systems will be presented. P38—Noncovalent Interactions of Long -Chain Perfluoroalkyl Acids with Serum Albumin Heather N. Bischel,1, * Laura A. MacManus-Spencer, 2 and Richard G. Luthy" * 'Department of Civil and Environmental Engineering, Stanford University, Stanford, CA; 2Department of Chemistry, Union College, Schenectady, NY Preferential distribution of long -chain perfluoroalkyl acids (PFAAs) in the liver, kidney and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulativc potential and in vivo bioavailability of PFAAs. In this work, association constants (Ka) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 106 M-1 with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10-3), corresponding to a high protein — water distribution coefficient (log Kpw > 4). Nanoelectrospray ionization mass spectrometry (nanoESl-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESl-MS are on the order of 105 M-1 for PFOA and PFNA and 104 M-1 for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios. P39—Perfluorochemicals and Perfluorochemical Precursors in Biosolids and Biosolids-Amended Soils Jennifer G. Sepulvado, Andrea Blaine, Brad Leick, Christopher P. Higgins Science and Engineering Division, Colorado School of Mines, Golden, CO The presence the perfluorochemicals (PFCs) and PFC precursors in municipal sludge has been well documented. However, recent concerns have arisen about the fate of PFCs present in municipal sludge processed for land -application (i.e., biosolids). When land applied, biosolids-borne PFCs have the potential to leach into potable water supplies and/or bioaccumulate into both animals and plants. PFC precursors, such as fluorotelomer-based chemicals and perfluoroalkyl sulfonamide -based chemicals, can be microbially transformed to PFCs, primarily under aerobic conditions. As wastewater sludge can be 53 DEQ-CFW 00000696 treated (digested) either aerobically or anaerobically, the type of treatment the sludge receives may have a substantial impact of the extent of transformation of PFC precursors to PFCs. This study examined the occurrence of PFCs in both aerobically and anaerobically digested sludges, finished biosolids destined for land application, and biosolids-amended soils. P40—Perfluorohexanesulfonate and Perfluorooctanesulfonate Decrease Plasma Cholesterol and Triglycerides in APOE*3LEIDEN.CETP Mice by Reducing VLDL Production and Increasing VLDL and HDL Clearance Elsbet J. Pieterman,1 Patrick C. N. Rensen,2 Annemarie C. E. Maas,1 Jose W. A. van der Hoorn, I Louis M. Havekes,i David J. Ehresman,3 Shu-Ching Chang,3 John L. Butenhoff,3 and Hans M. G. Princen' 'TNO BioSciences, Leiden, The Netherlands; 2Leiden University Medical Center, Leiden, The Netherlands, 33M Company, St. Paul, MN Perfluoroalkyls such as perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) have been found in biological samples in wildlife and humans. While laboratory studies have shown a reduction in serum cholesterol (TC) and triglycerides (TG) after treatment with PFOS and PFHxS, the 4-carbon homolog, perfluorobutanesulfonate (PFBS), does not affect these parameters. Certain observational epidemiological studies have been characterized as finding modest positive associations between serum concentrations of non -high density lipoprotein cholesterol (non-HDL-C) and serum concentrations of PFOS. However, collectively, these primarily cross -sectional investigations of occupational, community - exposed, and general populations are remarkably inconsistent for any dose -response relationship across a range of PFOS concentrations. These PFOS concentrations span three orders of magnitude between the least and highest exposed populations. In the present study, the effect of PFBS, PFHxS, and PFOS on cholesterol and triglyceride metabolism was investigated using male ApoE*3.Leiden. CETP mice, a transgenic mouse model on a C5761/6 background that was developed to resemble a human -like lipoprotein profile. Semi -synthetic cholesterol -rich control diet containing 0.25% (w/w) cholesterol, 1 % (w/w) corn oil, and 14% (w/w) bovine fat were given to all mice for 4 weeks period prior test compound administration. After the 4-week run-in period, groups of mice (n=6/group) received either control diet or control diet incorporated with PFBS (0.03%), PFHxS (0.006%), PFOS (0.003%) or positive control tenofibrate (0.03%) for an additional 4 — 6 weeks. The corresponding daily intakes were approximately 30, 6, 3, and 30 mg/kg/day for PFBS, PFHxS, PFOS, and fenofibrate, respectively. The collected data demonstrated that PFHxS and PFOS reduced plasma TG and TC in E3L.CETP mice by lowering both VLDL-LDL and HDL. Lowering of VLDL was the result of a decreased hepatic VLDL-TG and VLDL-apoB production and increased VLDL-TG clearance associated with increased TG hydrolase activity in plasma. Lowering of HDL was explained by decreased production and maturation related to decreased apoA1, ABCA1 and LCAT expression. These effects appeared to be dependent on the alkyl chain length, as PFBS had negligible effects. P41—Biodegradation of Polyfluoroalkyl Phosphates (Paps) and Fluorotelomer- Based Acrylate Polymers (FTACPS) in a Greenhouse Agrocosm Experiment Holly Lee, Keegan Rankin, Pablo J. Tseng, Alex Tevlin, and Scott A. Mabury Department of Chemistry, University of Toronto, Toronto, Ontario, Canada Following the discovery of elevated concentrations of perfluorinated acids (PFAs) in sludge -applied agricultural fields in Decatur, Alabama, land application of wastewater treatment plant (WWTP) sludge has been identified as a potential source of these chemicals to the soil environment. PFAs are ubiquitously disseminated in the environment, either through industrial emissions or environmental degradation of fluorinated materials, such as polymers and surfactants, used in commercial products. Comparisons of the concentrations of PFAs in background soils (up to —10 ng/g) to those in sludge - applied soils (up to —2500 ng/g) and present levels in WWTP sludge (up to —440 ng/g) show that in addition to the contribution of background PFAs in sludge, a significant portion of the present PFAs contamination in soil remains unaccounted for. The aim of the present study was to determine whether polyfluoroalkyl phosphates (PAPs) and/or fluorotelomer-based acrylate polymers (FTAcPs), which may be released into WWTP in residential waste, 54 DEQ-CFW 00000697 0 0 HO""'P-OCH2CH2(CF2)6F HO'P.-OCH2CH2(CF2)6F OH OCH2CH2(CF2)6F degrade into PFAs in a greenhouse soil -plant agrocosm. Briefly, the agrocosm consisted of sandy loam soil premixed with either PAPs or a model FTAcP and WWTP sludge, which were then potted and sown with seeds of alfalfa plants, Medicago truncatula. Control and experimental pots (n=3) were sacrificed at 0, 1.5, 3.5, and 5.5 months, where the plant tissue extracts were analyzed by LC-MS/MS, and soil extracts were analyzed by both LC-MS/MS and MALDI-ToF. The presences of PAPs and theirdegradation products in the plants indicate the potential for these fluorinated chemicals to contaminate the terrestrial food chain, ultimately leading to human exposure. Although FTAcPs analysis in soil samples is still preliminary, a characteristic peak pattern of the polymer on MALDI-ToF spectra allowed us to track its degradation by observing a decrease intensity for major peaks. These results suggest that FTAcPs may degrade under environmentally relevant conditions, and in addition to PAPs, could be a significant in direct source of PFAs. P42—Increased Expression of the Xenosensor Nuclear Receptors PPARa and CAR/PXR Results in Hepatocellular Hypertrophy and Cell Proliferation in Sprague-Dawley Rats Following Dietary Exposure to Ammonium Perfluorooctanoate Clifford R. Elcombe,1 Barbara M. Elcombe,1 John R. Foster,2 David G. Farrar,3 Reinhard Jung,4 Shu- Ching Chang, 5 Gerald L. Kennedy, 6 John L. Butenhofl5 'CXR Biosciences Ltd, Dundee, Scotland, UK; 2AstraZeneca Pharmaceuticals, Macclesfield, Cheshire, England, UK; 3lneos Chlor, Runcorn, England, UK; 4Clariant, Sulzbach am Taunus, Germany; 53M Company, St. Paul, MN; 6DuPont Company, Wilmington, DE Exposure to perfluorooctanoate (PFOA) produces hepatomegaly and hepatocellular hypertrophy in rodents. In mice, PFOA-induced hepatomegaly is associated with the activation of the xenosensor nuclear receptors, PPARa and CAR/PXR. Although non-genotoxic, chronic dietary treatment of Sprague- Dawley (S-D) rats with the ammonium salt of PFOA (APFO) produced an increase in benign tumors of the liver, acinar pancreas, and testicular Leydig cells. Most of the criteria for establishing a PPARa-mediated mode of action for the observed hepatocellular tumors have been shown to be satisfied with APFO with the exception of the demonstration of increased hepatocellular proliferation. The present study evaluates the potential roles for APFO-induced activation of PPARa and CAR/PXR with respect to liver tumor production in the S-D rat and as compared to the specific PPARa agonist, 4-chloro-6-(2,3-xylidino)-2- pyrimidinylthioacetic acid (Wy 14,643). Male S-D rats were fed APFO (300 ppm in diet) or Wy 14,643 (50 ppm in diet) for either 1, 7, or 28 days. Effects of treatment with APFO included: decreased body weight; hepatomegaly, hepatocellular hypertrophy, hepatocellular hyperplasia (microscopically and by 5-bromo-2- deoxyuridine (BrdU) labelling index), and hepatocellular glycogen loss; increased expression of PPARa- regulated genes (peroxisomal R-oxidation and microsomal CYP4A1 protein); decreased plasma triglycerides, cholesterol, and glucose; increased expression of CYP2131/2 (CAR regulated) and CAR/PXR-regulated CYP3A1. Responses to treatment with Wy 14,643 were consistent with activation of PPARa, specifically: increased CYP4A1 and peroxisomal R-oxidation; increased hepatocellular 55 DEQ-CFW 00000698 hypertrophy and cell proliferation; decreased apoptosis; and hypolipidemia. With the exception of decreased apoptosis, the effects observed with Wy 14,643 were noted with APFO, and APFO was less potent. These data clearly demonstrate an early hepatocellular proliferative response to APFO treatment and suggest that the hepatomegaly and tumors observed after chronic dietary exposure of S-D rats to APFO likely are due to a proliferative response to combined activation of PPARa and CAR/PXR. Cell proliferation can lead to selective clonal expansion of pre-neoplastic cells resulting in eventual tumor formation. If the chemically -stimulated cell proliferation is pivotal for the development of tumors, in light of the inability of the human receptors to support the stimulation of the cell proliferation and hyperplasia, then the exposure of humans to such PPARa/CAR/PXR agonists is unlikely to pose a liver cancer hazard. P43—Community Exposure in Minnesota: The East Metro Perfluorochemicals Biomonitoring Pilot Project Jean Johnson, Adrienne Kari, Al Williams, and Carin Huset Minnesota Department of Health, St. Paul, MN The East Metro Perflurochemicals Biomonitoring Pilot project, by the Minnesota Department of Health (MDH), characterized population exposures to perfluorinated chemicals (PFCs) among residents of several eastern suburbs in the Minneapolis -St. Paul Metropolitan Area. Contamination of drinking water supplies with PFCs in the East Metro area was first discovered in 2004. Subsequent investigation revealed widespread contamination of ground water that supplied drinking water to over 10,000 residents living in the City of Oakdale. In Lake Elmo, maximum levels of PFOA, PFOS and PFBA detected in private wells were 2.4, 3.5 and 12 ppb, respectively. In late 2006 and early 2007 levels above 1 ppb of PFBA were observed in water supply wells in the cities of Cottage Grove and St. Paul Park. As of January 1, 2008, MDH identified 169 private wells in the area that were contaminated with PFOA and/or PFOS >0.1 ppb. Study communities were located in proximity to PFC production and waste disposal facilities, and were selected based on known contamination of drinking water sources as follows: 1. People currently living in households in Lake Elmo and Cottage Grove with a private well with PFOA and /or PFOS contamination (>0.01 ppb) detected in at least one well water sample (n=169 households identified through well sampling records). 2. People currently living in households served by the City of Oakdale Municipal Water Supply (n=6, 655 households identified through municipal billing records). A total of 196 people, 98 from each of the two communities, were randomly selected and enrolled with informed consent. Participation was limited to adults 20 years or older who had lived in their current home prior to January 1, 2005. From August through December, 2008, blood serum specimens were collected from all participants and analyzed by the MDH public health laboratory for seven PFC compounds-- PFOA, PFOS, PFBA, PFBS, PFPeA, PFHxS and PFHxA--using solid phase extraction and liquid chromatography tandem mass spectrometry. We found measurable blood levels of PFOA, PFOS, and PFHxS in all 196 participants. PFOA geometric mean was15.4 ng/mL (range 1.6-177), PFOS geometric mean was 35.9 ng/mL (range 3.2-448), and PFHxS geometric mean was 8.4 ng/mL (range 0.32-316). Levels did not differ significantly between the two communities. Levels were higher in males and increased with age. Measurable levels of PFBA and PFBS were detected in a proportion of the participants, 28% and 3% respectively, while PFPeA and PFHxA were below the limit of detection (0.1) ng/mL for all 196 specimens. Among private well users with known levels of PFOA and PFOS in drinking water, contaminant levels, age and gender accounted for approximately 43% of variation in blood levels of PFOA and PFOS. 56 DEQ-CFW 00000699 P44—Toxicogenomic Profiling of Perfluorononanoic Acid in Wild -Type and PPARa-Null Mice M.B. Rosen,' J.R. Schmid,2 R.D. Zehr,3 K P. Das,3 H. Ren,4 B.D. Abbott 13 and C. Lau 'Integrated Systems Biology, zBiostatistics and Bioinformatics, 3Toxicology Assessment, 4Toxicogenomics Core, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC Perfluorononanoic acid (PFNA) is a ubiquitous environmental contaminant and a developmental toxicant in laboratory animals. Like other perfluoroalkyl acids (PFAAs) such as perfluorooctane sulfonate (PFOA) and perfluoroalkyl acid (PFOS), PFNA is a known activator of peroxisome proliterator-activated receptor - alpha (PPARa). In comparison to PFOA and PFOS, PFNA is a more potent activator of PPARa and displays greater acute hepatic toxicity. Male wild -type (WT) and PPARa-null (Null) mice were dosed by oral gavage with PFNA (1 or 3 mg/kg/day), or vehicle for 7 days. Animals were euthanized, livers weighed, and liver samples collected for preparation of total RNA. Gene profiling was conducted on 4 mice per group using Affymetrix 430_2 GeneChips. As expected, PFNA altered the expression of genes associated with a variety of PPARa-regulated functions in WT mice such as fatty acid/energy metabolism, inflammation, peroxisome biogenesis, and proteasome biogenesis. As observed for other PFAAs, activation of the constitutive androstane receptor (CAR) was indicated in both WT and Null mice. In Null mice, regulation of genes related to lipid metabolism was found as were changes related to inflammation and oxidative stress. Genes normally associated with activation of PPARa such as Acaal , Cyp4al4, Ehhadh, Mel, and Acoxl were up -regulated in Null mice as well. Thus, in addition to activation of PPARa, these data indicate that activation of CAR and presumably other PPAR subtypes such as PPARy may be found in PFNA-exposed mice. These results lend support to an increased understanding that, in addition to their primary mode of action as activators of PPARa, PFAAs such as PFNA have the potential to activate other nuclear receptors. (This abstract does not necessarily reflect EPA policy.) P45-13iomonitoring of PFAA in Adults and Children Exposed to Contaminated Drinking Water in Germany —Results of the Recent Follow -Up Studies Jurgen Holzer,' Thomas G6en,2 Sonja SchaubEdna Brede,' Johannes Muller,2 Knut Rauchfuss,3 Martin Kraft,3 Rolf Reupert,3 Peter Kleeschulte 4 and Michael Wilhelm' 'Department of Hygiene, Social and Environmental Medicine, Ruhr -University Bochum, Germany; 2Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University Erlangen - Nuremberg, Germany; 3North Rhine-Westphalia State Agency for Nature, Environment and Consumer Protection, Recklinghausen, Germany; 4Public Health Department of the Hochsauerlandkreis, Meschede, Germany Objective: In Arnsberg, Germany, about 40,000 residents have been exposed to PFOA (500-640 ng/I)- contaminated drinking water. In 2006, activated charcoal filtering was installed in the waterworks and PFC-concentrations in drinking water were lowered significantly. Human biomonitoring studies were performed in 2006 (immediately after filter -installation), 2007 and 2008. Details of the PFOA- contamination and the results of the first human biomonitoring study have been presented during PFAA days II. Here we report on the results of the follow up studies performed between 2007 and today. Study population: 90 children (5-6 years old), 164 mothers (23-49 years) and 101 men (18-69 years) took part in the first cross -sectional study 2006. Participation rate in the two year follow up study was 77 percent. 105 anglers have been included in another investigation to assess the impact of fish consumption from the PFAA-contaminated water bodies on the internal exposure to PFAA. Methods: Lifestyle factors and drinking water consumption habits were assessed by questionnaire and interview. Perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanoate (PFHxA), perfluorohexanesulfonate (PFHxS), perfluoropentanoate (PFPA) and perfluorobutanesulfonate (PFBS) in blood plasma and PFOA/PFOS in drinking water samples were measured by solid phase extraction, HPLC and MS/MS detection in the same laboratory. Results: In 2006, PFOA-concentrations in blood plasma of residents living in Arnsberg were 4.4-8.3 times higher compared to the reference population (ratios based on geo-metric means: children 22.1/4.8 pg/L, mothers 23.4/2.8 pg/L, men 25.3/5.8 pg/L). Two years later, geometric mean concentrations decreased 57 DEQ-CFW 00000700 (data for Arnsberg only; geometric means: children 13.7 pg/L, mothers 13.8 pg/L, men 20.2 pg/L). These numbers correspond to a decrease of 36 percent (children), 37 percent (mothers) and 18 percent (men), respectively. Based on a first order kinetics/one compartment model PFOA half-lives were estimated from these data (3 years for children and mothers). In fish consuming anglers distinctly elevated PFOS- concentrations were observed (1-649 pg/l, median: 31 pg/I; median of controls: 10 pg/1)). Conclusion: This most recent investigation of the German cohort confirms the slow elimination of PFOA in humans. Fish consumption from contaminated water bodies contributes substantially to the PFOS body burden. We will also report on blood tests performed in these populations (cholesterol, single cell gel electrophoresis). Acknowledgements: The studies were financed by the North Rhine Westphalia State Ministry for Environment and Nature Conservation, Agriculture and Consumer Protection. P46—Exposure to Perfluorononanoic Acid During Pregnancy: Evaluations of Rat and Mouse Models Kaberi P. Das,' Carmen Wood,' Dan Zehr,' Katoria Tatum-Gibbs,2 Brian Grey,' Mitch Rosen,' and Christopher Lau' Reproductive Toxicology Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC, USA; 2Curriculum in Toxicology, UNC, Chapel Hill, NC, USA. Perfluorononanoic acid (PFNA) is a persistent environmental contaminant. Although its levels in the environment are lower than those of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA), its presence in humans is rising and is of concern. Previous studies have indicated developmental toxicity of PFOS and PFOA in the laboratory rodent models. The current study examines developmental toxic effects of PFNA in rats and mice. PFNA was given to timed -pregnant Sprague-Dawley rats from GD1-21 and to CD-1 mice from GD 1-17 by oral gavage daily at 1, 3, and 5 mg/kg; controls received water. Like PFOS and PFOA, PFNA did not affect maternal weight gain, number of implantations, fetal viability or fetal weight in both species. Maternal hepatomegaly and minor delays in anatomical development of the fetus were noted both in rats and mice. Mouse pups were born alive and survival in the 1 and 3 mg/kg PFNA groups was not different from that in controls. In contrast, 80% of 5 mg/kg PFNA exposed mice neonates died within the first 10 days of life, whereas no neonatal death was observed in the rat. However, PFNA-induced neonatal death differed somewhat from that induced by PFOS or PFOA, in that PFNA-exposed pups survived a few days longer than those exposed to PFOS or PFOA, which typically died within the first 2-3 days of postnatal life. In rat pups exposed to 5 mg/kg PFNA had significantly lower birth weight than controls (16%), which remained lower than controls through early postnatal development. Surviving mice neonates exposed to PFNA exhibited dose -dependent deficits in growth and development (eye-opening, onset of puberty). In addition, increased liver weight seen in PFNA-exposed offspring persisted into adulthood and was likely related to the persistence of the chemical in the tissue. Evaluation of gene expression in fetal and neonatal livers revealed robust activation of peroxisome pro[iferator-activated receptor -alpha (PPARa) genes and molecular signals by PFNA that resembled the response of PFOA. Our results indicate developmental toxicity of PFNA comparable to that of PFOA, suggesting these effects are common to perfluoroalkyl acids that persist in the body. This abstract does not necessarily reflect U.S. EPA policy. P47—Retrospective Exposure Estimation for Perfluorooctanoic Acid (PFOA) for Participants in the C8 Health Project Hyeong-Moo Shin,' Ver6nica Vieira,2 P. Barry Ryan,3 Russell etwiler,' Brett Sanders,' Kyle Steenland,3, 4 Scott Bartell' 'University of California -Irvine, Irvine, CA; 2Boston University, Boston, MA; 3Emory University, Atlanta, GA; 4C8 Science Panel, Atlanta, GA Background/Aims: The primary source of perfluorooctanoic acid in the environment of eastern Ohio and western West Virginia is believed to be the DuPont Washington Works facility. Percolation of aerially deposited perfluorooctanoic acid downwards through the soil and pumping by industrial and municipal wells near the contaminated Ohio River is thought to explain elevated well water concentrations observed DEQ-CFW 00000701 in six municipal water districts and human serum concentrations measured in recent years. Our objective is to estimate historical perfluorooctanoic acid exposures and historical serum concentrations experienced by each of the participants in the C8 Health Project who consented to share their residential histories, excluding those who reported ever depending on bottled water, those who had missing residential histories during any of the 16 years prior to the serum samples, and those who identified past or present DuPont employment. Methods: We linked several environmental fate and transport models including AERMOD, PRZM3, BREZO, MODFLOW, and MT3D to simultaneously model PFOA air dispersion, transit through the unsaturated soil zone, surface water transport, and groundwater flow and transport. Annual PFOA exposure rates were estimated for each individual based on predicted calibrated water concentrations and predicted air cuncentratiuns, individual residential histories, and default assumptions from the EPA Exposure Factors Handbook. Individual exposure estimates were coupled with a one -compartment pharmacokinetic model to estimate time -dependent serum concentrations for 31,517 participants. Results: Prior to calibration, predicted water concentrations were within 2.1 times the observed mean water concentrations for all six municipal water districts. Using calibrated water concentrations, predicted and observed median serum concentrations in 2005-2006 are 12.1 and 24.5 ppb, respectively (Spearman's rho = 0.66). Conclusion: Our linked fate and transport and toxicokinetic models predict recently observed municipal water concentrations reasonably well and only slightly under -predict observed serum concentrations. These models will be used to produce individualized retrospective exposure estimates for a variety of epidemiologic studies being conducted in this region. Keywords: Perfluorooctanoic Acid (PFOA), Environmental fate and transport models, Serum concentrations P48—Developmental Toxicity of Perfluorononanoic Acid in the Wild -Type and PPAR-alpha Knockout Mouse After Gestational Exposure Wolf CJ,' Zehr RD,2 Schmid JE,2 Lau C,' and Abbott BD1 'Toxicology Assessment Division, 2Research Core Unit, NHEERL, ORD, USEPA, Research Triangle Park, NC Perfluorononanoic acid (PFNA) is a perfluoroalkyl acid detected in the environment and in tissues of humans and wildlife, and its concentration in human serum has increased in the past few years. PFNA negatively affects development and survival of CD1 mice and activates peroxisome proliferator-activated receptor -alpha (PPARa) in vitro. Our objective was to characterize the developmental effects and serum levels of PFNA in 129S1/SvlmJ wild type (WT) and PPARa-knockout (KO) mice after gestational exposure, and determine the dependence of PFNA toxicity on PPARa. Sperm positive WT and KO females were dosed orally with water (vehicle control; 0.01 ml/g), 0.83, 1.1, 1.5, or 2 mg/kg PFNA on gestational days (GD) 1-18 (day of plug = GD 0). Dams and pups were monitored daily and euthanized at postnatal day 21 (pups) or 42 days post -coitus (adults). Serum was collected from adults and from 2 pups per litter. Dam weight gain during gestation, uterine implantation and pup birth weight were not affected by treatment in either strain. The number of live pups at term and the survival of offspring to weaning were drastically reduced in WT 1.1 and 2 mg/kg groups (p< 0.05, p< 0.001). Pup eye opening was delayed by 2 days and postnatal pup weight was reduced in WT at 2 mg/kg. None of these endpoints was affected in the KO. Relative liver weight at weaning in both dams and pups was increased in all treated WT groups (p< 0.001), but only in the highest dose group in KO dams and pups (p< 0.001). PFNA was present in the serum of all mice in a dose -dependent manner and levels were higher in treated animals compared to controls (p< 0.0001). Serum levels of PFNA were generally higher in pups than in dams. In dams, serum levels of PFNA were higher in WT than in KO. In pups, PFNA levels were higher in KO compared to WT (p< 0.0001), despite no adverse developmental effects in KO. These results suggest that effects of PFNA on pup development, survival to weaning, and liver weight in dams and pups are dependent on PPARa. This abstract does not necessarily reflect USEPA policy. 59 DEQ-CFW 00000702 P49—Fast Food Consumption and Other Dietary Measures Predict PFC Serum Concentrations in the U.S. Population Jessica W. Nelson, Alicia J. Fraser, Elizabeth E. Hatch, Madeleine K. Scammell, and Thomas F. Webster Department of Environmental Health, Boston University School of Public Health, Boston, MA Background. Polyfluoroalkyl chemicals (PFCs) have been detected in humans world-wide. Exposure is hypothesized to be primarily through diet, though specific sources are poorly understood. Objectives. We studied whether serum concentrations of PFCs were related to intake of certain food groups and fast food in a sample of the U.S. population. Methods. We analyzed data from the 2003-2004 National Health and Nutrition Examination Survey (n=1,866). Using multiple linear regression, we examined the association between perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) and self -reported intake of seven food groups and fast food (overall and specific types). Results. PFOA and PFNA were positively associated with fast food consumption; people who ate more than 1 fast food item per day had PFOA concentrations approximately 15% higher (95% confidence interval, 4 to 25%) than those who ate none. We saw a similar relationship with take-out hot coffee and soft drinks; the latter were associated with PFOS as well. PFOS and PFNA were also positively associated with intake of red meat, PFOS and PFOA with potatoes, and all three with salty snacks. Conclusions. The observed relationships between serum PFCs and red meat, potatoes, and snacks are consistent with past studies. For the first time, we also found a positive association with fast food, independent of food group intake. These exploratory results suggest that PFCs may enter the food chain both through bioaccumulation and contact with packaging. Our findings regarding take-out coffee and soft drinks are novel and must be investigated further. P50—A Profile of Human PPAR mRNA and Protein Expression During Development Andrew Watkins, Carmen R. Wood, Kaberi P. Das, and Barbara Abbott USEPA, ORD, NHEERL, Toxicity Assessment Division, Developmental Toxicology Branch, RTP, NC Peroxisome proliferator-activated receptors (PPAR) are nuclear hormone receptors that regulate lipid and glucose homeostasis and are important in reproduction and development. PPARs are targets of pharmaceuticals and are also activated by environmental contaminants, including perfluorinated alkyl acids. Animal studies have characterized the expression of PPAR a, R, and y in mouse and rat, but little is known about PPAR expression during human development. In this study, gestation day 54-125 human fetal adrenal, heart, intestine, kidney, liver, lung, spleen, stomach, and thymus, , were obtained from the Birth Defects Research Laboratory at the University of Washington, Seattle. Quantitative PCR was used to evaluate mRNA and Western blot for protein expression of PPAR a, R, and y. Changes in mRNA expression with increasing age of the fetus were detected and included increasing PPARa and PPARP in liver, decreasing PPARR in heart and intestine, and decreasing PPARy in adrenal. The abundance of fetal PPAR mRNA was compared to adult human samples (First Choice Human Total RNA, Ambion, Inc.). In intestine, fetal and adult PPAR expression was the same, while in stomach and heart all PPARs had lower expression in fetus. PPARy in liver and PPAR(3 in thymus were expressed in higher levels in fetal tissue. In the kidney and spleen, PPARa and PPAR(3 were lower and in lung and adrenal. PPARy was lower in the embryo than in adult. Relative expression of PPARa, R, and y varied by tissue. Western blots showed no changes in protein with age for any PPAR isoform in the liver, heart, spleen, stomach or thymus. PPARs increased in intestine with age. Decreasing protein with age occurred for PPARa in kidney, lung and adrenal. PPAR(3 decreased in adrenal and PPARy decreased in kidney. This study profiles human PPAR protein and mRNA expression during development. In general, all PPAR isoforms were detected in all organs and expression appeared stable. Also, with some exceptions, mRNA levels were similar to adult or lower in fetus. This study provides new information regarding human fetal expression of PPAR and will be important in evaluating the potential for developing human to respond to PPAR agonists. DEQ-CFW 00000703 ,F P51—Decline of Perfluorooctanoic Acid in Human Serum Over Two Years Before and After Granular Activated Carbon Filtration in Two Public Water Supplies, and Implications for Half -Life Estimation Scott M Bartell', Christopher Lyu2, P Barry Ryan 3, and Kyle Steenland3 'Program in Public Health, University of California, Irvine, CA; 2Battelle/Centers for Public Health Research and Evaluation, Durham, NC; 3Emory University, Atlanta, GA Background: Perfluorooctanoic acid has been detected in public water supplies in several water districts near the DuPont Washington Works facility in West Virginia. Two of these water districts, Little Hocking Water Association and Lubeck Public Service District, began granular activated carbon filtration during 2007 in order to remove the contaminant. Methods: Up to 7 blood samples were collected from each of 200 participants, from May 2007 until June 2009. Primary drinking water source varied over time for some participants; our analyses were grouped according to water source at baseline (149 participants served by Lubeck and 51 participants served by Little Hocking). Log concentration random effects models were used to estimate serum half-lives. Results: Median serum concentrations in May -June 2007 were 89 ng/mL for Lubeck participants and 325 ng/mL for Little Hocking participants. During the first year of the study, average decreases in serum concentrations were 26% for Lubeck and 24% for Little Hocking, yielding a median half-life estimate of 2.3 years. During the second year of follow-up, average decreases in serum concentrations were 9% for Lubeck and 15% for Little Hocking. Conclusions: Serum perfluorooctanoic acid concentrations did not fall as rapidly in the second year as they did during the first year. Possible explanations include ongoing exposures from sources other than the two public water districts and/or pharmacokinetics that are not well described by a one -compartment model with first -order elimination. P52—Distribution of Perfluorooctanesulfonate and Perfluorooctanoate into Human Plasma Lipoprotein Fractions over a Wide Range of Concentrations John L. Butenhofi;' Elsbet J. Pieterman,2 David J. Ehresman,I Geary W. Olsen,' Shu-Ching Chang, Hans M. G. Princen2 13M Company, St. Paul, MN; 2TNO BioSciences, Leiden, The Netherlands Certain observational epidemiological studies have been characterized as finding modest positive associations between serum concentrations of non -high density lipoprotein cholesterol (non-HDL-C) and serum concentrations of PFOS and/or PFOA. However, collectively, these primarily cross -sectional investigations of occupational, community -exposed, and general populations are remarkably inconsistent for any dose -response relationship across a range of PFOS and/or PFOA concentrations. These PFOS and PFOA concentrations span three orders of magnitude between the least and highest exposed populations. Contrary to the epidemiological positive associations, toxicological studies of PFOS and PFOA in laboratory animals, including cynomologus monkeys, have observed either no change in serum lipids or decreases in serum cholesterol and/or triglycerides. These conflicting observations suggest that the reported epidemiologic associations of serum PFOS and PFOA with serum cholesterol may have biological, but not causal, significance. A possible non -causal hypothesis for the reported epidemiological associations between serum PFOS and/or PFOA and serum cholesterol is that PFOS and/or PFOA have affinity for and distribute into serum lipoprotein fractions. Thus, it can be postulated that, as serum lipoprotein concentration increases, distribution of PFOS and PFOA into serum lipoprotein fractions and total serum PFOS and/or PFOA concentrations would increase correspondingly. The study reported herein was undertaken to test the latter hypothesis through investigation of the effect of plasma concentration of PFOS and PFOA on the proportion of plasma PFOS and PFOA bound to the human plasma lipoprotein fractions VLDL, LDL, and HDL at background general population serum PFOS and PFOA concentrations and in serum spiked with either approximately 0.19 or 19 pM PFOS or PFOA. Plasma from a senior investigator was obtained and used to represent general population background concentrations of PFOS and PFOA, as well as to prepare approximately 0.19 and 19 pM concentrations of each fluorochemical. All experiments were performed in triplicate. Fractionation of 300 pL plasma into 61 DEQ-CFW 00000704 25 fractions was accomplished by density gradient ultracentrifugation using both Redgrave and iodixanol density gradients. For each density gradient, fractions were pooled into very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and lipoprotein depleted plasma (LPDP) fractions as well as intermediate fractions based on determination of cholesterol concentrations in each of 25 fractions. Both density gradients were adjusted to give clean separations between the lipoprotein fractions and between HDL and albumin contained in LPDP. PFOS and PFOA concentrations in pooled fractions were determined by LC-MS/MS with lower limits of quantitation (LLOQ) ranging from 10 — 25 pg/mL. Total recovered mass of PFOS and PFOA based on duplicate determinations of initial concentrations ranged from 71 — 84% and 95 — 109% for PFOS and from 82 — 102% and 96 — 110% for PFOA for Redgrave and iodixanol density gradients, respectively. The majority of PFOS and PFOA recovered mass was found in LPDP (52 — 60% and 87 — 104% of PFOS mass and 81 — 98% and 94 — 109% of PFOA mass for Redgrave and iodixanol density gradients, respectively). Percent of mass recovered from fractions 1 —19 (lipoprotein -containing fractions) ranged from 17 — 24% and <5 — 9% for PFOS and from <4 - <8% and <1 - <4% for PFOA for the Redgrave and iodixanol density gradients, respectively. PFOS concentrations in LDL and HDL were clearly higher than in VLDL and intermediate pooled lipoprotein fractions. For both PFOS and PFOA, there was minimal difference between concentrations tested and the resulting proportion distributed to the various pooled fractions. The results using the iodixanol method may be more representative physiologically, as iodixanol is a water soluble, non-ionic fluid. The iodixanol data suggest that maximally 9% of PFOS may be distributed to lipoprotein - containing fractions in plasma, yet only 1 % or less of PFOA is so distributed. Taken together, these data do not support a strong role for plasma lipoprotein fractions in explaining the inconsistent dose -response associations reported in observational epidemiological studies. P53—Title: Occupational Exposure to Ammonium Perfluorooctanoate: Exploring Two Exposure Models to Account for Workers' Exposure Over Time Katherine K. Raleigh,' Bruce H. Alexander,' Gurumurthy Ramachandran,' Sandy Z. Morey,2 Perry Logan,2 Geary Olsen2 'University of Minnesota, School of Public Health, Division of Environmental Health Sciences; 23M Company, St. Paul, MN Introduction: Human health effects of perfluorooctanoic acid (PFOA) exposure continue to he characterized. Primary limitations of occupational epidemiology studies are exposure models and availability of data to accurately estimate body burden. The goal of this research was to compare a standard cumulative exposure model with a biologically relevant clearance -weighted exposure model that incorporates the long half-life of PFOA for all workers employed at an ammonium perfluorooctanoate (APFO) production facility. To accomplish this, we created a detailed exposure data matrix (EDM) to be used in our exposure reconstruction. From the EDM we assigned daily air concentrations to workers for each day of employment. These concentrations were specific to the worker's job title, and where and when they worked. We explored the extent of exposure misclassification by comparing the workers' cumulative and clearance -weighted exposure profiles. Methods: Detailed exposure profiles were created for all workers who worked at the Cottage Grove, 3M facility in Minnesota over the 50 years that APFO was manufactured. Air monitoring data, production records and professional judgment were used to capture exposure concentrations by job title, department, and year. The duration of time spent in three distinct work periods was calculated for a typical eight hour day and included; 1) time spent on PFOA tasks within production rooms, 2) time spent on non-PFOA tasks within production room, and 3) time spent outside of production rooms. An air concentration, in mg/m3, was determined for each of the three periods and a time weighed average for the eight hour shift was calculated for every unique year, job title and department combination. Time - weighted averages (TWA in mg/m3) were calculated for more than 3,000 unique combinations —all of which incorporated frequency and duration of tasks. Workers held multiple jobs throughout their tenure and accordingly the number of days at each job was multiplied by the corresponding TWA to estimate annual exposures for cumulative and time period specific exposure estimates. We estimated body burden using the US EPA's exposure factor handbook's breathing rate of 1.0 m3 per hour for an average adult doing light work. Two exposure models of PFOA annual internal dose estimates (in mg) included a LV DEQ-CFW 00000705 cumulative exposure model, and a clearance -weighted exposure model to account for the elimination half-life of PFOA. Results: The daily TWAs for Spray Dry Operators, Assistant Operators and Helpers were categorized as part of the highest exposure jobs. These TWAs ranged from 0.080 mg/m3 to 0.379 mg/m3. The rankings of the workers by estimated internal dose changed based on the model chosen given the workers'unique exposure profiles, and the within -worker dose estimates varied by time period. Conclusion: The choice of exposure model will influence both within and between worker APFO exposure classifications. These estimates of internal dose and enhanced exposure classification of APFO will be useful for future studies with tirrre-varying close estimates for assessing health outcomes based on body burden of PFOA. P54—Exposure to Perfluorooctanoic Acid (PFOA) and Plasma Lipid Concentrations in Young Girls Susan M. Pinney,' Frank M. Biro,2,3 Robert Herrick,' Lusine Yaghjyan,1 Antonia Calafat,4 Kayoko Kato Paul Succop,1 M. Kathryn Brown,' Ann Hernick,1 Robert Bornschein' 'University of Cincinnati College of Medicine, Dept. of Environmental Health, Cincinnati, OH; 2University of Cincinnati College of Medicine, Dept. of Pediatrics, Cincinnati, OH; 3Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 4Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA Background: Polyfluoroalkyl compounds (PFCs) and their salts, such as perfluorooctanoic acid (PFOA), have been reported to bind to peroxisome proliferators-activated receptors in animals and result in hypolipidemia and lower cholesterol levels. Humans are less sensitive to PPAR-a, with expression levels approximately 10 times less than in mice. In studies of workers at production plants, community residents living nearby, and in the 2003-2003 National Health and Nutrition Examination Study, serum PFOA concentration was found to be associated with higher serum total cholesterol. Studies have differed in their finding of the association between low density cholesterol and PFOA serum concentrations. Methods: Within the NIH Breast Cancer and the Environment Research Centers (BCERC), we conducted a study of multiple environmental biomarkers, including PFOA and other PFCs in serum of young girls (age 6-7 years at entry, N=379 girls). Plasma lipid measures were obtained using blood samples collected at the first examination of this prospective study. We examined the relationship between PFOA serum concentration and plasma lipid concentrations. Linear regression models included PFOA (both log transformed and three exposure level groups), age at the examination, race (African -American versus all other), and body mass index (BMI) z scores. Results: Detectable serum levels of five PFCs, including PFOA, were found in >95% of the girls. The PFOA median was 7.9 ng/ml (range <LOD 0.1 to 55.9 ng/ml), with 37.4% having values above the 95tn percentile for children 12-19 years in the NHANES 2003-2004 population (8.6 ng/ml). The median values of PFOA in the three exposure groups were 5.9, 9.8 and 18.3 ng/ml. Using linear regression analyses, we found no statistically significant association between log -transformed serum PFOA concentration and plasma level of triglycerides, total cholesterol, and non-HDL cholesterol. We found a borderline statistically significant relationship (p.0.07) between HDL cholesterol and PFOA exposure group 2 compared to the baseline group, but not when group 3 was compared to baseline. In these analyses, very little of the variance in the lipids was explained by PFOA. The most important predictors were BMI z score and race. Conclusions. Unlike other human studies of adults, we have not found a relationship between PFOA and total cholesterol and non-HDL cholesterol in young girls. We continue to explore these complex relationships in models including other covariates. Support for this project provided by the National Institute of Environmental Health Sciences and the National Cancer Institute, to the University of Cincinnati/Cincinnati Children's Hospital Medical Center, Breast Cancer & the Environment Research Center (U01 ES12770), and Center for Environmental Genetics (P30-ES06096). 63 DEQ-CFW 00000706 The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. P55—Perfluorinated Compounds in Swedish Blood and Breast Milk 1997-2009 Anna Karrman,' Ulrika Eriksson,' Bert van Bavel,' Lennart Hardell,' Marie Aune,2 and Gunilla Lindstrom 'MTM Research Centre, School of Science and Technology, Orebro University, Sweden; 2Swedish National Food administration, Uppsala, Sweden Human blood and breast -milk from Sweden were analysed for perfluorinated compounds (PFCs) in order to study presence and temporal trend after the phase -out and regulatory actions taken to minimize usage and release of some chemicals, mainly perfluoroctane sulfonate (PFOS). Human whole blood was collected in connection with epidemiological studies during year periods 1997-2000 and 2008-2009. Different cohorts were studied and to get the best representative analysis only males were selected for assessing temporal trends, however the median age still differed between the two groups (31.6 years for 1997-2000 (n=40) and 67.4 years for 2008-2009 (n=120)). Composite breast milk samples from 25-90 individuals were collected annually from primiparae women year 1996 to 2008, a total of 12 samples. Most prevalent and found at highest concentrations in human blood and milk was PFOS. Preliminary results show that the blood median concentration in 1997-2000 was 17.7 ng/mL while 13.3 ng/mL in 2008-2009, meaning a 25% reduction in ten years. In breast milk the concentration declined from 0.35 ng/mL to 0.14 ng/mL corresponding to a 60% reduction. PFOA also decreased from 2.7 ng/mL whole blood in 1997-2000 to 1.9 ng/mL in 2008-2009 (30% reduction). In breast milk the PFOA level was 0.16 ng/mL in 1996 and twelve years later 0.11 ng/mL (31 % reduction). The third and last compound detected in breast milk was PFHxS, 0.03 ng/mL in 1996 and 0.09 ng/mL in 2008. In whole blood the reduction under the same period was 49%, from 1.72 ng/mL to 0.88 ng/mL. The coefficient of variation in the analysis is typically 10% for whole blood but up to 30% for breast milk due to higher uncertainty associated with low ppb levels. These results indicate that PFOS, PFOA are decreasing in Swedish humans probably as a result of restrictions in the usage of those compounds in Sweden and other countries. Contradictory results were seen for PFHxS, while reducing in blood the milk levels increased. This indicates that different exposure sources for PFHxS and PFOS exists. For higher chain length carboxylates the trend is different, with similar or increasing blood levels. PFNA and PFDA increased with 119 and 53% and PFUnDA with 16%. Even though the blood levels are low compared to PFOS and PFOA (<1 ng/mL) these results indicates that longer chain carboxylates are increasing and should be monitored for possible negative effects. P56—Concentrations of Perfluorooctanesulfonate and Perfluorooctanoic Acid in Human Males and Their Associations with Semen Parameters James H. Raymer,' Larry C. Michael,' William S. Studabaker;' Geary Olson,2 Carol S. Sloan,' Timothy Wilcosky,3 and David Walmer4 'RTI International; 23M Corporate Occupational Medicine; 3University of North Carolina, Chapel Hill, NC; 4Duke University Medical Center In Vitro Fertilization Clinic, Durham, NC Background: Toxicologic effects of PFOS and PFOA in rats have generally been observed with blood concentrations orders of magnitude higher than those measured in the general human population. In rats, PFOS and PFOA had inconsistent impacts on reproductive hormone concentrations and reproductive outcomes. A recent study of human males reported a statistically significant decrease in the median sperm counts between low and high PFA exposure groups. Objectives: The objective was to evaluate whether or not serum concentrations of PFOA, PFOS, and PFHS were associated with perturbation in semen quality or reproductive hormones including testosterone and estradiol. Methods: A total of 256 men were recruited from those who presented with their partners to the Duke University fertility clinic for an assessment. Blood and semen were collected and analyzed for PFOA and DEQ-CFW 00000707 PFOS, FSH, LH, prolactin, estradiol, T3, T4, and free and total testosterone. Logistic and linear modeling were performed with semen profile measurements as outcomes and PFOS, PFOA, PFOS*PFOA interaction in semen and plasma as explanatory variables, controlling for age and duration of abstinence. Results: Prolactin, LH, TSH, and triiodothyronine were related to concentrations of PFOS in plasma in a positive manner at the 0.02 significance level. PFOA in plasma was positively associated with concentrations of LH in plasma. PFOS in plasma and semen were highly correlated. Conclusions: Although there is an indication that perfluorinated compound concentrations were inconsistently associated with hormone concentrations, there is essentially no indication that exposure was associated with any semen characteristics, except possibly abnormal viscosity. Acknowledgments: This work was supported by NIEHS Grant 5R01 ES11683-3 and 3M Corporation. P57—A Temporal Trend Study (1972-2008) of Perfluorooctanesulfonate, Perfluorohexanesulfonate, and Perfluorooctanoate in Pooled Human Milk Samples from Stockholm, Sweden Maria Sundstrom,' David J. Ehresman,2 Anders Bignert,3 John L. Butenhoff,2 Geary W. Olsen,2 Shu- Ching Chang, 2and Ake Bergman' Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden; 23M Company, St. Paul, MN; 3Department of Contaminant Research, Swedish Museum of Natural History, Stockholm, Sweden Human exposure to perfluoroalkyls, in particular perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), has been studied increasingly over the past decade. However, human serum concentrations of PFOS, perfluorohexanesulfonate (PFHxS), and PFOA have been in decline since circa 2000 — 2002. The purpose of this study was to evaluate whether a parallel trend of these analytes could be observed in human milk. This study evaluated pooled Swedish human milk samples from 1972 — 2008 for concentrations of PFOS, PFHxS, and PFOA. The 20 samples which formed the 2007 pool were also analyzed as individual samples. Analyses were performed by HPLC-MS/MS. All three analytes showed statistically -significant increasing trends from 1972 through the 1990s, with concentrations reaching a plateau in the 1990s. In 1972, the measured concentrations of PFOS, PFHxS, and PFOA in pooled human milk were 25 pg/mL, <5 pg/mL, and 19 pg/mL, respectively. In 2000, the respective concentrations of PFOS, PFHxS, and PFOA in pooled human milk were 213 pg/mL, 24 pg/mL, and 124 pg/mL. During 2001 — 2008, PFOA and PFOS showed statistically -significant decreasing trends. Although PFHxS also showed a decreasing trend during 2001 — 2008, this trend was not statistically significant. In 2008, the measured concentrations of PFOS, PFHxS, and PFOA in pooled human milk were 75 pg/mL, 14 pg/mL, and 74 pg/mL, respectively. PFOS was the predominant analyte present in the pools during most years. Due to the complexities of the human milk matrix and the requirement to accurately quantitate low pg/mL concentrations, meticulous attention was paid to background contamination to ensure that accurate results were obtained. For example, in the present study, there were pg/mL concentrations of all three analytes in factory sealed bottles of formic acid. The temporal concentration trends of PFOS, PFHxS and PFOA observed in human milk are parallel to those reported in the general population serum concentrations. P58—Exposure to Polyfluoroalkyl Chemicals and Attention Deficit Hyperactivity Disorder in U.S. Children Aged 12-15 Years Kate Hoffman,' Thomas F. Webster,' Marc G. Weisskopf,2 Janice Weinberg,3 and Ver6nica M. Vieira' 'Department of Environmental Health, Boston University School of Public Health, Boston, MA; 2Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology, Harvard School of Public Health, Boston, MA; 3Department of Biostatistics, Boston University School of Public Health, Boston, MA Introduction: Polyfluoroalkyl chemicals (PFCs) have been widely used in consumer products. Exposures in the US and world populations are widespread. PFC exposures have been linked previously to various health impacts, and data in animals suggest that PFCs may be potential developmental neurotoxicants. W. DEQ-CFW 00000708 Objectives: We evaluated the associations between exposures to four PFCs and parental report of diagnosis of attention deficit hyperactivity disorder (ADHD). Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2003-2004 for children aged 12-15 years. Parental report of a previous diagnosis by a doctor or healthcare professional of ADHD in the child was the primary outcome measure. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) levels were measured in serum samples from each child. Results: Of the 586 children in the sample, 51 had a prior diagnosis of ADHD. When PFOS was treated as a continuous predictor, a 1.03 fold increased odds was observed for each I g/L increase in serum PFOS after adjustment for confounding (95% Cl 1.01-1.05). There were also significant dose response relationships between PFOA and PFHxS levels and ADHD (OR=1.12; 95% Cl 1.01-1.23 and OR=1.06; 95% Cl 1.02-1.11 respectively). Similarly, children with higher PFNA levels were more likely to have ADHD (OR=1.32; 95% Cl 0.86-2.02). Conclusions: Our results, using cross -sectional data, are consistent with increased odds of ADHD in children with higher serum PFC levels. Given the extremely prevalent exposure to PFCs, follow-up of these analyses with cohort studies is needed. P59—Perfluorinated Carboxylic Acids in Directly Fluorinated High Density Polyethylene Material: A New Source of Human Exposure Amy A. Rand and Scott A. Mabury Department of Chemistry, University of Toronto, Toronto, Ontario, Canada Perfluorinated carboxylic acids (PFCAs) are ubiquitous in the environment and have been detected in human blood worldwide. The contamination of PFCAs in humans is not well understood therefore it is necessary to determine the potential routes of exposure. One potential route of exposure is the direct exposure to PFCAs through contact with polymers that have been directly fluorinated. Direct fluorination is a reactive gas post -treatment process in which hydrogen atoms on polyolefin plastics are replaced with fluorine, utilized to improve the barrier properties of bottles, jars, tanks, and films through surface modification. Each year, over 300 million polyethylene and polypropylene bottles, containers, and articles are surface modified. Due to the fluorination treatment process, it is hypothesized that PFCAs may form on the fluorinated polyolefin material, thus providing a potential source of human exposure. This investigation attempts to detect and quantify PFCAs found in 0.95 L directly fluorinated high density polyethylene (HDPE) bottles. The bottles varied by the extent to which they have been fluorinated, marked by fluorination levels 1 through 5. Bottles were soxhlet extracted, the methanol concentrated via evaporation and reconstituted in 80:20 water:methanol, and PFCAs of varying chain length were detected and quantified using LC-MS/MS. Concentrations ranged from 0.49 ± 0.04 to 70.02 ± 38.09 ng of total PFCAs/bottle, with the highest concentrations corresponding to the perfluoropropanoic, perfluorobutanoic, and perfluorohexanoic acids at 54.83 ± 32.89, 70.02 ± 38.09, and 33.62 ± 0.43 ng/bottle respectively. The relative concentrations of PFCAs changed depending on the fluorination level, and also increased with increasing fluorination level. P60—Preliminary Results on Subfecundity and Plasma Concentrations of Perfluorinated Compounds During Pregnancy in the Norwegian Mother and Child Cohort Study, 2002-2004 KW Whitworth,' LS Haug,2 DD Baird,' G Becher,2 JA Hoppin,' M Eggesbo,2 R Skjaerven,2 C Thomsen,2 and MP Longnecker' 'National Institute for Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services; 2Norwegian Institute of Public Health, Oslo, Norway Perfluorinated compounds (PFC) are ubiquitous and persistent organic pollutants. Further, a recent study reported a positive association between maternal serum concentrations of PFCs and subfecundity [1]. The goal of the present study was to examine PFCs and subfecundity in another population and consider the effect of parity on this association. DEQ-CFW 00000709 This study is based on the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health and consists of >100,000 pregnancies from 1999-2008. Among women enrolled from 2002-2004, we randomly selected 400 cases (women with planned pregnancies and time -to -pregnancy (TTP)>12 months) and 550 cohort members with a TTP. The definition of cases (women with planned pregnancies and TTP>12 months) and controls (women with planned pregnancies and TTP 512 months) were applied to the random cohort resulting in 30 additional cases and 509 controls. Women missing age or pre -pregnancy body mass index (BMI) were excluded leaving 425 cases and 499 controls for analysis. Second -trimester plasma PFC concentrations were analyzed using liquid chromatography/tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for PFC quartiles using logistic regression, adjusted for maternal age, BMI and parity (yes/no). We also examined results stratified by parity. The median serum PFOS was 13.1 ng/ml (interquartile range=10.3-16.6 ng/ml); the median serum PFOA was 2.3 ng/ml (interquartile range=1.7-3.0 ng/ml). We found no association between subfecundity and PFC levels. After stratification by parity, we found elevated ORs for PFOS and PFOA in parous women only. Parous women in the highest PFOS quartile had 60% greater odds (OR=1.6, 95% C1=0.9-2.8) of subfecundity compared with parous women in the lowest quartile while nulliparous women in the highest PFOS quartile had 30% reduced odds (OR=0.7, 95% C1=0.4-1.3) of subfecundity compared with nulliparous women in the lowest quartile. Similarly, parous women in the highest PFOA quartile had 80% greater odds (OR=1.8, 95% C1=0.9-3.7) of subfecundity compared with parous women in the lowest quartile while nulliparous women in the highest PFOA quartile had 40% reduced odds (OR=0.6, 95% C1=0.3-1.2) of subfecundity compared with nulliparous women in the lowest quartile. The p-value for interaction between parity and PFOS was 0.14 and parity and PFOA was <0.01. We found no evidence of an association between PFC levels and subfecundity overall. We observed substantial effect measure modification between parity and PFC levels. The pharmicokinetics of PFCs during and following pregnancy may explain the present study's observation of one direct subfecundity- PFC association among parous women. Women appear to incur a decrease in PFC levels following delivery and lactation after which levels begin to rise again. The longer the interval between a woman's most recent delivery and current conception, the longer she has for blood levels to rise to pre -pregnancy levels. Among parous women, all else being equal, TTP may be a marker of time between most recent birth and the index pregnancy. Retrospective studies, like ours, that present overall effect estimates on fecundity in parous and nulliparous women combined could create the appearance of an adverse effect when none exists [2]. 1. Fei, C.Y., et al., Maternal levels of perfluorinated chemicals and subfecundity. Human Reproduction, 2009. 24(5): p. 1200-1205. 2. Olsen, G.W., J.L. Butenhoff, and L.R. Zobel, Perfluoroalkyl chemicals and human fetal development. - An epidemiologic review with clinical and toxicological perspectives. Reproductive Toxicology, 2009. 27(3-4): p. 212-230. P61—Exposure of Norwegian Infants to Perfluorinated Compounds Line S. Haug,' Cathrine Thomsen,' Azemira Sabaredzovic,' Kristine B. Gutzkow,' Gunnar Brunborg,' and Georg Becher'.2 'Norwegian Institute of Public Health, Department of Analytical Chemistry, Oslo, Norway; ZUniversity of Oslo, Department of Chemistry, Oslo, Norway Introduction: Perfluorinated compounds (PFCs) have been found widespread in the environment and in humans' 2. Several PFCs have long elimination half-lives in humans3 Animal studies have demonstrated hepatotoxicity, developmental toxicity, immunotoxicity as well as hormonal effectsz. Some of the PFCs are therefore considered as persistent organic pollutants (POPs). Exposure to POPs in utero is of special concern as the fetus is highly vulnerable to toxicant exposure. Further, evaluation of infant exposure to environmental chemicals through breast-feeding is of particular concern in Norway where the mothers are among the most persevering breast -feeders in the world. The aim of this study was to explore the prenatal exposure to PFCs and the infants' exposure from breast milk. Materials and Methods: Concentrations of PFCs were determined in paired samples of maternal and umbilical cord blood plasma (n=244), paired samples of serum and breast milk (n=38), as well as in 67 DEQ-CFW 00000710 samples of breast milk from nine mothers who collected samples monthly from about two weeks after birth and up to twelve months (n=70). All analyses were performed using column switching LC-MS/MS methodology as described previously4,a Results and Discussion: Up to seven PFCs were detected in the paired samples of maternal and umbilical cord blood plasma. The maternal and fetal levels were significantly correlated (Spearman rank correlations, p<0.01) for perfluorohexane sulfonate (PFHxS, r=0.66), perfluorooctane sulfonate (PFOS, r-0.75), perfluorooctanoic acid (PFOA, r=0.85), perfluorononanoic acid (PFNA, r=0.62) and perfluoroundecanoic acid (PFUnDA, r-0.47). The concentrations of perfluorotridecanoic acid (PFTrDA) were below or close to the limit of quantification (LOQ) in most samples, and perfluorodecanoic acid (PFDA) was observed above the LOQ in only four of the cord blood samples; thus it was therefore not possible to assess the correlations for these compounds. The relative proportion of PFHxS was higher than that of PFOS in cord blood compared to maternal blood, and it was higher for PFOA than for PFNA and PFUnDA (p<0.01). This indicates that the chain length of the fluorinated compound is an important determinant for placental passage. The mean PFC concentration (ng/ml) in cord blood was 34 to 84% of the maternal concentration. PFC concentrations were determined in paired samples of serum and breast milk from 19 Norwegian mothers. In the majority of the breast milk samples, concentrations >LOQ were observed for only PFOS and PFOA. The concentrations ranged from 0.04-0.25 (median 0.087) and 0.025-0.83 (median 0.041) ng/ml breast milk, respectively. Breast milk concentrations were only 1.4 and 3.8% of the serum concentrations for PFOS and PFOA, respectively, and the relationships were linear with correlation coefficients of 0.63 (n=19) and 0.99 (n=10). Assuming a consumption of 700 nil breast milk/day the intakes from breast milk are 61 and 29 ng/day for PFOS and PFOA, respectively. Correspondingly, a dietary intake of 113 and 44 ng/day has been estimated for the adult Norwegian populations. To study rates of elimination through breastfeeding nine primiparae mothers (and one mother breast feeding her second child) collected breast milk samples monthly from about two weeks after birth and up to twelve months. Using linear mixed effect models the depuration rates for PFOS and PFOA were calculated to be 3.1 and 7.7% per month, respectively (p<0.01)5. To summarize briefly; several PFCs were detected in the umbilical cord blood plasma, which demonstrate that PFCs are transferred to the fetus via the placenta. Further, we have shown that even though the PFC concentrations in breast milk are about two orders of magnitude lower than i in serurn, lactation Is still a significant source of exposure for the infant. References:'Houde, M., Martin, J.W., Letcher, R.J., Solomon, K.R., Muir, D.C.G., 2006. Biological monitoring of polyfluoroalkyl substances: A review. Environ. Sci. Technol. 40, 3463-3473. 2Lau, C., Anitole, K., Hodes, C., Lai, D., Pfahles-Hutchens, A., Seed, J., 2007. Perfluoroalkyl acids: A review of monitoring and toxicological findings. Toxicol. Sci. 99, 366-394. 3O1sen, G.W., Burris, J.M., Ehresman, D.J., Froehlich, J.W., Seacat, A.M., Butenhoff, J.L., et al., 2007. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ. Health Perspect. 115, 1298- 1305. 4Haug, L.S., Thomsen, C., Becher, G., 2009. A sensitive method for determination of a broad range of perfluorinated compounds in serum suitable for large-scale human biomonitoring. J. Chromatogr. A 1216, 385-393. 5Thomsen, C., Haug, L.S., Stigum, H., Froshaug, M., Broadwell, S.L., Becher, G. Changes in concentrations of perfluorinated compounds, polybrominated diphenyl ethers and polychlorinated biphenyls in breast milk during twelve months of lactation. Manuscript. 6Haug, L.S., Thomsen, C., Brantsarter, A.L., Kvalem, H.E., Haugen, M., Becher, G., et al. Diet and particularly seafood are major sources of perfluorinated compounds in humans. Submitted March 2010. DEQ-CFW 00000711 P62—Hazard Evaluation of 6-2 Fluorotelomer Alcohol (6-2 FTOH), 1,1,2,2-Tetrahydroperfluorooctanol T Serex,' S Mun/ey,1 C Carpenter,' M Donner,' R Hoke,' R Buck ,2 and S Loveless' 'DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE; ZDuPont Chemical Solutions Enterprise, Wilmington, DE 6-2 Fluorotelomer alcohol (6-2 FTOH) was evaluated for acute, genetic, subchronic, reproductive, developmental, and aquatic toxicity. 6-2 FTOH was slightly toxic by the oral and dermal routes with an oral LD50 of 1750 mg/kg and a dermal LD50 > 5000 mg/kg in rats, and did not produce a dermal sensitization response in mice. 6-2 FTOH was not mutagenic in the bacterial reverse mutation test or in the mouse lymphoma assay and was not clastogenic in a chromosome aberration assay in human lymphocytes. 6-2 FTOH was moderately toxic to aquatic organisms. The 96-hour LC50 in fathead minnows was 4.8 mg/L, 48-hour EC50 in Daphnia magna was 7.8 mg/L, and 72-hr EC50 in Pseudokirchneriella subcapitata was 4.5mg/L. In subchronic, one -generation reproductive, and developmental toxicity studies, 6-2 FTOH was administered to rats by oral gavage. Mortality was observed in the subchronic study at 125 and 250 mg/kg/day; the deaths occurred after about three weeks of dosing and continued sporadically. Other effects observed at these doses included decreased body weights, changes in organ weights, and pathological findings involving the liver and kidneys as well as effects on the teeth. Observations at 125 and 250 mg/kg/day in the reproductive study included reduced litter size, increased pup mortality during lactation, reduced uterine weights, and reduced offspring weights. Effects in the developmental study were limited to increased incidences of skeletal variations, lower maternal body weights and food consumption at 125 and 250 mg/kg/day. There was no maternal mortality nor were there any test substance -related gross observations in the developmental study. There was no effect on fetal body weight or litter sex ratio and there were no effects on the incidences of fetal resorptions or malformations at any dose level. These data indicate 5 mg/kg/day is the NOAEL for this test substance based on the most sensitive endpoint of histopathological changes in the rat liver at 25 mg/kg/day in the subchronic study. P63—Branched Isomer Profiles of Perfluoroalkyl Carboxylates in Japanese Environment Mitsuha Yoshikane,1 Yasuyuki Shibata,' and Naoto Shimizu` 'National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan; 2Agilent Technologies Ltd., Tokyo, Japan In the analysis of fluorosurfactants in terrestrial environment of Japan, we frequently observed the second peak which precedes the peak corresponding to the linear perfluoroalkyl carboxylic acids (PFCAs), such as PFOA, PFNA and PFDA. Both peaks showed basically identical parent / daughter ions in a Q-pole type LC/MSMS as well as in high resolution LC/Q-TOF, with differences in retention time and the relative peak intensities among several daughter ions. Here we report the identification and distribution profiles of these preceding peaks. By the comparison with the standards of branched isomers, the preceding peak of PFOA was found to be identical to a branched isomer, perfluoro-6-methylheptanoic acid, while the other branched isomers, such as those with 3-methyl or 4-methyl group, were not detected. Although standards of branched isomers of other PFCAs (such as PFDA or PFNA) are not available, fragment patterns in MSMS and Q-TOF analysis supported the view that all the preceding peaks in PFCAs correspond to the isomers with a branched methyl group at the far end of the chain from carboxyl group, like in the case of PFOA. Such specific branched isomers at the terminal position may be produced by the telomerization process started from perfluoropropene. The branched isomers were detected in many different types of samples collected in various places, suggesting wide distribution of such isomers in Japanese environment. Occasionally the branched peaks exceed those of linear isomers, indicating further research needs to reveal origins and environmental fate of these branched isomers as well as their toxicities. DEQ-CFW 00000712 P64—Derivation of Health -Based Criteria for Perfluorobutyric Acid (PFBA), Perfluorooctanoic Acid (PFOA), Perfluorobutane Sulfonate (PFBS), and Perfluorooctane Sulfonate (PFOS) Goeden, Helen, Rita Messing, Pamela Shubat, and Paul Moyer Minnesota Department of Health, St. Paul, MN Perfluorochemicals (PFCs) are a family of manmade chemicals used to make products that resist heat, oil, stains, grease and water, including nonstick cookware, stain -resistant carpets and fabrics; as components of fire -fighting foam; and in other industrial applications. Minnesota is one of the few states in the United States where these chemicals were manufactured. The 3M Company made PFCs at its Cottage Grove, MN, facility beginning in the 1950s. Wastes from the production process were placed in several local disposal sites, resulting in subsequent widespread groundwater contamination. The chemical structures of PFCs make them extremely resistant to breakdown in the environment. Unlike other persistent chemicals PFCs are very soluble in water and are bound to protein in blood rather than sequestered in fat. Most of the information regarding potential health effects of perfluoroalkyl compounds has come from studies in laboratory animals. Effects observed in these studies include liver effects, alterations in lipid metabolism, developmental delays, alteration in thyroid hormone levels, and altered immune function. One of the unusual aspects of PFCs Is that the half-life in the human body can be more than 200-fold longer than the half-life in a laboratory animal. PFCs therefore present unique challenges for risk characterization. The Minnesota Department of Health (MDH) evaluates health risks from contaminated groundwater and establishes human health -based values (drinking water concentrations without appreciable risk to human health). MDH has utilized new risk characterization methodology to derive health -based guidance for several PFCs. The derivation process included: 1) assessing evidence of life stage sensitivity; 2) assessing the relationship between effects observed and duration of exposure; 3) selecting endpoints based on characterization of the entire database rather than the "critical' study; 4) utilizing a human equivalent dose rather than administered dose; 5) incorporating duration specific water intake rates; and 6) comparing calculated HRL values for different durations to ensure that the final values are protective of human health at each stage of life. This methodology was used to derive health based criteria for PFBA, PFOA, PFBS, and PFOS. A major challenge encountered in the derivation process involved addressing interspecies extrapolation toxicokinetic issues (e.g., significant species differences in elimination rates), estimation of internal dose levels at steady state conditions, as well as toxicodynamic issues such as human sensitivity to adverse effects. The derivation process also demonstrated that the historic reliance on chronic assessments may not always be protective of less -than -chronic exposures. Reference doses (RfDs) for each PFC were derived from a human equivalent dose (HED) based on steady-state conditions. The time to reach steady-state conditions equates to a duration of approximately 3 - 5 half-lives. The information necessary to estimate less than steady-state HEDs is currently not available. Based on a mean PFBA human half-life of 3 days, steady-state conditions would be established within approximately 9 to 15 days. Therefore, short-term (up to 30 days), subchronic (30 days to 10% of a life span) and chronic (greater than 10% of a life span) duration RfDs were derived. Corresponding time - weighted water intake rates were estimated for each duration. The resulting calculated health based values were 7, 8 and 10 ug/L for short-term, subchronic and chronic, respectively. Longer duration values must be protective of the periods of higher exposure which occur within the longer duration period. Therefore, the final subchronic and chronic health -based values for PFBA were set at the short-term value of 7 ug/L. Unlike PFBA, the half-life of PFOA in humans is nearly 4 years and the time necessary to reach steady- state conditions would be approximately 11 to 19 years. Therefore only a chronic RfD was derived. A 70 DEQ-CFW 00000713 corresponding time -weighted water intake rate was estimated resulting in a chronic health -based value for PFOA of 0.3 ug/L. Based on a mean PFBS human half-life of 30 days, steady-state conditions would be established within approximately 3 to 5 months. Therefore, only subchronic and chronic duration RfDs were derived. Corresponding time -weighted water intake rates were estimated for each duration. The resulting calculated health based values for PFBS were 9 and 7 ug/L for subchronic and chronic exposures, respectively. Like PFOA, PFOS has a long half-life in humans (more than 5 years) and the time necessary to reach steady-state conditions would be approximately 16 to 27 years. Therefore only a chronic RfD was derived. A corresponding time -weighted water intake rate was estimated resulting in a chronic health - based value for PFOS of 0.3 ug/L. P65—Measuring for Perfluorinated Chemicals in Land -Applied Biosolids and Plants Kim Harris, Kenneth Gunter, Gerald Golubski, Bradley Grams;' Christopher Lau, Marc Mills, Mark Strynar, John Washington, Shoji Nakayama;2 Christopher Higgins3 and Lakhwinder Hundal� 'US EPA -Region 5, Chicago, IL; 2US EPA Research Triangle Park, NC; 3Colorado School of Mines, Golden, CO; Metropolitan Water Reclamation District of Greater Chicago, Chicago, IL Perfluorinated chemicals (PFCs) consist of a diverse group of compounds characterized by their unique chemical -physical properties. Because of their widespread use in industrial and consumer applications, PFCs eventually reach wastewater treatment plants (WWTPs) through industrial discharge, wastewaters generated by the cleaning of PFC-treated products, leaching of plastic products and indirect nonpoint sources. As such, WWTPs may be a major route of PFCs to the environment since conventional WWTPs have proven to be ineffective in removing PFCs, and under certain processes can increase concentrations. With respect to possible modes of human exposure and risk, several studies have shown significant concentrations of PFCs in generated WWTP sludge (biosolids). As such, there is concern for land application of biosolids since this commonly used waste disposal practice could present direct exposure routes through consumption of foods and crops. This concern has boon highlighted recently by a contamination event in Decatur, Alabama, where elevated levels of PFCs were found and traced back to treated municipal biosolids that was applied to 4900 acres of rural land used for grazing cattle and crops. Although crops fertilized with PFC-containing biosolids may be an important exposure route to humans, few studies have attempted to estimate the transfer potential of PFCs from soil to plant. As little data exist regarding the levels of PFCs in soils after land application or plant uptake resulting from this practice, our study is designed to examine whether detectable levels of PFCs are found in soil and plants of areas where biosolids had been land applied as fertilizer generated from mixed industrial and domestic waste facilities. In addition, we will conduct a controlled study in the field to assess the uptake of PFC in a variety of plants grown in contaminated biosolids. P66—Perfluorophosphonic Acids, Polyfluoroalkyl Phosphoric Acids, and Perfluoro-4-Ethylcyclohexane Sulfonate in Canadian Rivers Amila O. De Silva,' Brian Scott,' Mark Sekela,2 Melissa Gledhill,2 Myriam Rondeau,2 Sean Backus,2 and Derek Muir' 'Aquatic Ecosystem Protection Research Division, 2Water Quality Monitoring and Surveillance, Environment Canada, Ottawa, ON, Canada Mono- and di -substituted polyfluoroalkyl phosphoric acid (mono- and di-PAPs) and perfluoroalkylphosphonic acids (PFPAs) are polyfluorinated chemicals that are used in to provide water and oil repellency in food -contact packaging, and as foam stabilizers in personal care products and pesticide formulations. Previous studies indicated PAPs undergo metabolism and biodegradation to produce perfluorocarboxylates (PFCAs), suggesting PAPs may be a significant source of PFCA exposure 71 DEQ-CFW 00000714 F H F F F FFFFFFFF OH CH -0-9. F C'H 2 2 R OH FFFFFFFFF rY\10 F_ 8:2-diPAP in humans. The PFPAs are a high production volume chemical (>4000 kg/y 1998-2002). PFPAs are resistant to degradation and are recalcitrant similar to the highly persistent perfluorocarboxylates (PFCAs). In 2006, the USEPA prohibited the use of PAPs and PFPAs in pesticide formulations used for food crops, indicating concern over these chemicals in the environment. Perfluoro-4-ethylcyclohexane sulfonate (PFECHS) is currently used as an abrasion inhibitor in aircraft hydraulic fluids, however, there is no data currently available on its environmental distribution. In order to gain an rmderstanding of the distribution of these compounds in Canada, water was sampled from freshwater ecosystems. Analysis of di-PAPs ((OH)(0)P(OCH2CH2(CF2)X,yF)2, where x and y = 4,6,8,or 10), PFECHS and PFPAs (F(CF2)XP(0)(OH)2, where x = 6, 8, or 10) was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS) with quantification using authentic standards. Using measured flow rates at sampling stations permitted the calculation of mass flows of these chemicals. The 6:2 diPAP and C8 PFPA was detected in all samples with some contribution from longer and shorter chain length homologues. The highest concentrations were observed in Wascana Creek (50 ng/L 6:2 diPAP, 2 ng/L C8 PFPA) in the province Saskatchewan at a site downstream of a large wastewater treatment plant serving the city of Regina. Unline PFPAs and diPAPs, PFECHS was prevalent (1 ng/L) in the fast flowing St. Lawrence River at concentrations. Monthly samples are currently being acquired to study seasonality and sources. P67—Perfluorinated Acids in Freshwater Fish in Canada Amila De Silva,' Melissa Gledhill,2 Mark Sekela,2 Jim Syrgiannis,2 Marlene Evans,' Alain Armellin,2 Joe Pomeroy,2 Mike Keir,2 and Sean Backus2 Aquatic Ecosystem Protection Research Division, 2Water Quality Monitoring and Surveillance Division, Environment Canada, Ottawa, ON, Canada In 2008, Environment Canada embarked on an exhaustive national sampling campaign to assess contamination of freshwater ecosystems with perfluorinated acids by acquiring surface water and top predator fish samples. In this study, fish were caught from 21 sites across Canada with its north, south, west and east extremities represented by Great Bear Lake (66 N, 121 W), , Lake Erie (42 N, 81 W), Frederick Lake (48 N, 124 W), and Kejimkujik (44 N, 65 W). From each site 10 to 20 fish were caught: lake trout (Salvelinus namaycush), walleye (Sander vitreus), or yellow perch (Percy flavescens). After measuring weight and length, the entire fish was homogenized. Subsamples (0.2 g) were extracted using acetonitrile and carbon solid -phase extraction clean-up for analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, stable isotopes of 15N and 3C were determined to assess trophic position and carbon source. Perfluorooctane sulfonate (PFOS) concentrations ranged from non - detect (nd, <0.1 ng g-1) to 100 ng g-1 wet weight. The highest concentrations were observed in lake trout from Lake Erie, followed by Lake Ontario (50 ng g-1). PFOS was <1 ng g-1 in fish from the lakes north of 54 N. Walleye and lake trout from the St. Lawrence river had moderate concentrations of PFOS (25 ng g-1). Perfluorocarboxylates (PFCAs) from C8 to C14 were also determined. Lake Athabasca trout had the highest concentrations in the northern remote locations with the PFCA pattern dominated by C9, C11 and C13. Exceptions to this pattern of contamination were noted in fish from two sampling locations in the province of Saskatchewan where C10 was 3 times higher than any other PFCA. Both of these sites 72 DEQ-CFW 00000715 were reservoirs formed by dams. Surprisingly, lake trout from the eastern site Lake Kejimkujik in a national park in Nova Scotia, contained the highest concentrations (6 ng g-) of C11 and C13 compared to any other site. These fish were the youngest (1 to 2 y) and smallest (100 g) in the data set. Analysis in stable isotopes indicated a wide spread in the sample set with delta N15 ranging from 8 to 18 per mil and delta C13 ranging from -20 to -32 per mil. Although there are likely differences in the base of the foodwebs, a statistically significant correlation was observed between In PFOS concentration and delta N15. P68—Parsimonious Development of a Physiologically -Based Pharmacokinetic Model for PFOA John Wambaugh, Chester Rodriguez, Jimena Davis, Hugh Barton, and R. Woodrow Setzer 'National Center for Computational Toxicology, US EPA, Research Triangle Park, NC; 2Office of Pesticide Programs, US EPA, Washington, DC; 3Pfizer, Inc., PDM PK/PD Modeling, Groton, CT We examine pharmacokinetic (PK) models of varying complexity with respect to a large data set for female CD1 mice (Lau et al.) exposed to a range of single and repeated oral doses of PFOA. These data can be broadly grouped into 1) plasma concentrations 2) liver and kidney concentrations, and 3) liver weights. Depending upon the model assumed, different data groups can be predicted. For simple empirical (e.g. one -compartment) models or the "saturable resorption" model of Andersen et al. (2006), only plasma concentrations can be predicted. For more complicated physiologically -based PK (PBPK) models specific tissue concentrations, including kidney and liver, as well as liver weights can all be predicted. Adding model complexity requires sufficient data to parameterize the additional dynamics. We use Bayesian analysis to examine on a case -by -case basis whether models of varying complexity are supported by the available data. We consider a physiologic kidney with glomerular filtration and saturable resorption of PFOA from the proximal tubules; a growing liver with growth proportional to PFOA concentration in the liver; and dynamic, saturable plasma binding of PFOA. We use our results to establish the minimal PBPK model supported by the available data. We then compare the predictions of this model to limited PFOA data for male CD1 mice (Lau et al.) and female C57/136 mice (DeWitt et al.). P69—Title: Two Sites with PFOA and PFOS Contamination in the Southeast, USA Lee Thornas and Connie Roberts USEPA Region 4, Atlanta, GA In the past two years EPA Region 4 has spent a significant amount of resources addressing two sites with PFOA and PFOS contamination of groundwater and surface water. Several industries in Decatur, Alabama have used or manufactured PFOA and PFOS and have discharged these products to the WWTP. For 12 years (1996 to 2008), these biosolids from Decatur Utilities WWTP were used as a soil amendment on about 5000 acres of privately owned agricultural fields in Lawrence, Morgan and Limestone Counties. Sampling was conducted of domestic sludge, private water supply wells and surface water that indicated impacts from this activity. In Dalton, Georgia, carpet manufactures discharged effluent to a WWTP. The liquid effluent from the WWTP was land applied. The solid sludge was turned to compost and distributed over a large area. Surface water and groundwater is known to be impacted in the Dalton area. P70—Evidence for the Involvement of Xenobiotic-Responsive Nuclear Receptors in Transcriptional Effects upon Perfluoroalkyl Acid Exposure in Diverse Species Hongzu Ren,',2 Beena Vallanat,',2 David M. Nelson,3 Leo W.Y. Yeung,4,5 Keerthi S. Guruge,4 Paul K.S. S Lois D. Lehman-McKeeman,3 and J. Christopher Corton' 2,s Lam, 'NHEERL/ORD, US EPA, Research Triangle Park, NC; 2NHEERL Toxicogenomics Core, US EPA, Research Triangle Park, NC; 3Discovery Toxicology, Bristol-Myers Squibb Company, Princeton, NJ; 4Safety Research Team, National Institute of Animal Health, Tsukuba, Ibaraki, Japan; 5Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, PR China Humans and ecological species have been found to have detectable body burdens of a number of perfluorinated alkyl acids (PFAA) including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate 73 DEQ-CFW 00000716 (PFOS). In mouse and rat liver these compounds elicit transcriptional and phenotypic effects similar to peroxisome proliferator chemicals (PPC) that work through the nuclear receptor peroxisome proliferator- activated receptor alpha (PPAR alpha). Recent studies indicate that along with PPAR alpha other nuclear receptors are required for transcriptional changes in the mouse liver after PFOA exposure including the constitutive activated receptor (CAR) and pregnane X receptor (PXR) that regulate xenobiotic metabolizing enzymes (XME). To determine the potential role of CAR/PXR in mediating effects of PFAAs in rat liver, we performed a meta -analysis of transcript profiles from published studies in which rats were exposed to PFOA or PFOS. We compared the profiles to those produced by exposure to prototypical activators of CAR, (phenobarbital (PB)), PXR (pregnenolone 16 alpha-carbonitrile (PCN)), or PPAR alpha (WY-14,643 (WY)). As expected, PFOA and PFOS elicited transcript profile signatures that included many known PPAR alpha target genes. Numerous XME genes were also altered by PFOA and PFOS but not WY. These genes exhibited expression changes shared with PB or PCN. Reexamination of the transcript profiles from the livers of chicken or fish exposed to PFAAs indicated that PPAR alpha, CAR, and PXR orthologs were not activated. Our results indicate that PFAAs under these experimental conditions activate PPAR alpha, CAR, and PXR in rats but not chicken and fish. Lastly, we discuss evidence that human populations with greater CAR expression have lower body burdens of PFAAs. This abstract does not reflect EPA policy. P71—Preliminary Assessment of Developmental Toxicity of Perfluorinated Phosphonic Acid in Mice Katoria Tatum,` Kaberi Das, 2 Brian Grey,2 Mark Strynar,3 Andrew Lindstrom,3 and Christopher Lau2 'Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC; 2Toxicity Assessment Division, NHEERL; 3Human Exposure and Atmospheric Sciences Division, NERL, ORD, US EPA, RTP, NC Perfluorinated phosphonic acids (PFPAs) are a third member of the perfluoroalkyl acid (PFAA) family, and are structurally similar to the perfluoroalkyl sulfonates and perfluoroalkyl carboxylates. These emerging chemicals have recently been detected in the environment, particularly in surface water and in effluent of wastewater treatment plants. PFPAs are used primarily as a surfactant defoaming agent in the textile industry, pesticide production. Previous studies from our laboratory have identified developmental toxicity associated with gestational exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). The current study examines the potential adverse developmental effects of PFPA in the mouse. A mixture of PFPAs (Masurf-780) was given to timed -pregnant CD-1 mice by oral gavage daily throughout gestation (GD 1-17) at doses of 5, 10, 20, 30 or 40 mg/kg; controls received deionized water vehicle. PFPA did not alter maternal weight gains, but increased maternal liver weight significantly at 30 and 40 mg/kg. The chemical exposure did not influence the number of live fetuses or fetus weight except the 40 mg/kg group where mortality was observed. In contrast, fetal liver weights were enhanced at doses greater than 10 mg/kg. Neonatal survival and growth were generally not altered except in the 40 mg/kg group, but the increases in liver weight persisted. These results thus suggest that PFPA exposure during pregnancy did not compromise neonatal survival and postnatal growth as seen with PFOS and PFOA, but the hepatic effects appeared to be similar to these chemicals. This abstract does not necessarily reflect U.S. EPA policy. P72—A Data Mashup Model of Perfluorinated Chemicals in Global Plasma Measurements: Exposure Biomarkers or Nutritional Epidemiology? Michael -Rock Goldsmith and Peter Egeghy U.S. EPA's National Exposure Research Laboratory, RTP, NC To better understand how to interpret and potentially make use of human exposure biomarkers of perfluorinated chemicals (PFCs) in a global context, and how dietary mechanisms (i.e. bioaccumulation / food chain) may contribute we have comprehensively aggregated human plasma/serum PFC levels (namely PFOA and PFOS) from the literature by geographical location (biomarkers by country for - Australia, Belgium, Brazil, Canada, China, Columbia, Denmark, Germany, India, Italy, Japan, Korea, Malaysia, Netherlands, Peru, Poland, Spain, Sri Lanka, Sweden, USA). Next, in a visual exploration of the data, the normalized total PFOS/PFOA (mol/L) were used to create a color -graded global map of human PFC exposure biomarkers using IBM's social visual analytics tools (www.manv-eves.com). Due to 74 DEQ-CFW 00000717 a startling resemblance between these maps and the FAO's "Consumption of Meat" map (1999-2001)' we began to explore the dietary/food-web/far-field exposure scenarios that have begun to emerge in various research streams internationally (e.g. EC's Perfoods Seventh Framework Program -).2 Integrating international dietary variables into a global exposure biomarker model by using data collected by the United Nation's FAOSTAT (Food and Agriculture Organization of the United Nations) food supply data as a dietary intake proxy, broken down by bulk food (type/quantitity, Le meat/vegetable) on a normalized basis was used in a regression analysis with the global biomarker data. Additionally, the UN's Human Development Index4 was used as a proxy where food data would be unavailable, and functions of PFC plasma biomarkers as functions of both dietary and HDI data were developed, Pach with Rz > 0 8 Finally, these simple regression models were extrapolated onto a global map and national map to estimate "tar-tield" levels on a relative basis as a tunction of HUI or dietary tactors. Despite the crudeness of these models that are based on several underlying assumptions that relate either global dietary markers with global socioeconomic variables to a specific exposure biomarker endpoint (i.e. data mashup models) these simple correlations could prove useful in indentifying point - source contaminations by estimating background PFC levels as required in risk assessments for the general global population, as well as extending themselves in the field of dietary biomarkers and/or nutritional tracers (i.e. nutritional epidemiology). Future work geared towards a national (i.e. non -global) basis will include a more detailed analysis of the dietary components of NHANES journal entries for which PFC biomarkers have been collected, to extend these approaches to national levels and near -field exposures. Disclaimer: This Document does not reflect US -EPA policy. The appearance or absence of product, services, companies, organisations, home pages or other websites in this presentation does not imply any endorsement or non -endorsement thereof and reflects the views of the scientist alone. P73—Modeling Bioaccumulation as a Potential Route of Riverine Foodweb Exposures to PFOS B. Rashleigh,' R.A. Park,2 J. Clough,3 R. Bringolf,4 P.J. Lasier,5 M.C. Wellman' 'U.S. Environmental Protection Agency; 2EcoModeling; 3Warren Pinnacle Consulting, Inc.; 4University of Georgia; 5U.S. Geological Survey Perfluorinated acids are compounds of interest as bioaccumulators; these persistent chemicals have been found in humans and animals throughout the world. Perfluoroctane sulfonate (PFOS) has an especially high bioconcentration factor in fish, due to the stability of PFOS in the environment and its ability to bind to proteins. Few models are available for modeling the effects of PFOS on aquatic ecosystems; one is AQUATOX, an aquatic ecosystem simulation model that simulates the fate and effects of stressors on multiple species of algae, invertebrates, and fish in diverse waterbody types. In AQUATOX, PFOS sorption to sediments and algae are modeled empirically; bioaccumulation in animals is modeled based on perfluoroalkyl chain length. To date, PFOS has been simulated with AQUATOX for an estuarine system. Future applications are using a linked -segment version for spatially explicit modeling of rivers. ' http://www.fao.org/flleadmin/templates/ess/img/galleries/global_food_and_agricultural_perspectives_map_presentation/mapO8.gif 2 Project Acronym: PERFOOD Project Reference: 227525 hftp://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=1&CAT=PROJ&RCN=91268 ) 3 ( hftp://faostat.fao.org/site/345/default.aspx—) 4 See also: http://en.wikipedia.org/wiki/List_of_countries_by_Human_Development_index 75 DEQ-CFW 00000718 P74. Male Reproductive System Parameters in a Two -Generation Reproduction Study of Ammonium Perfluorooctanoate in Rats and Human Relevance Raymond G. York', Gerald L. Kennedy, Jr. b, Geary W. Olsen', John L. Buteiilioff,M 'RG York and Associates, 7598 Ashlind Circle, Manlius, NY, 13104; bDuPont Company, Chestnut Run Plaza, Building 708, Wilmington, DE, 19805; 'Medical Department, 3M Company, St. Paul, MN Ammonium perfluorooctanoate (ammonium PFOA) is an industrial surfactant that has been used primarily as a processing aide in the manufacture of fluoropolymers. The environmental and metabolic stability of PFOA together with its presence in human blood and long elimination half-life have led to extensive toxicological study in laboratory animals. Two recent publications based on observations from the Danish general population have reported: 1) a negative association between serum concentrations of PFOA in young adult males and their sperm counts; and 2) a positive association among women with time to pregnancy. A two -generation reproduction study in rats was previously published (2004) in which no effects on functional reproduction were observed at doses up to 30 mg ammonium PFOA/kg body weight. The article contained the simple statement: "In males, fertility was normal as were all sperm parameters". In order to place the recent human epidemiological data in perspective, herein we provide the detailed male reproductive parameters from that study, including sperm quality and testicular histopathology. Sperm parameters in rats from the two -generation study in all ammonium PFOA treatment groups were normal and reflected the normal fertility observations in these males. No evidence of altered testicular and sperm structure and function was observed in ammonium PFOA-treated rats whose mean group serum PFOA concentrations ranged up to approximately 50,000 ng/mL. Evidence from male worker populations, where mean serum PFOA concentrations ranged from two to four orders of magnitude higher than concentrations found in the general population, did not show any consistent changes in serum reproductive hormone levels that could be associated with a decrease in reproductive function. Similarly, male cynomolgus monkeys given daily oral capsules containing ammonium PFOA for six months had no observable alterations in testicular structure or sex hormones at group mean serum concentrations ranging up to approximately 110,000 ng/mL. Given that median serum PFOA in the Danish cohorts was approximately 5 ng/mL, it seems unlikely that concentrations observed in the general population, including those recently reported in Danish general population, could be associated with a real decrement in sperm number and quality. DEQ-CFW 00000719 PFAA Days III Agenda I US EPA 0 Lo. A Vex. Or http://www.epa.gov/riheerl/pfaa—days_3/agenda.html 2 7 76) cl, days 3.1agenda.htrn! itrJ sr4 Lost updated on Tnesday, June 01, 2010 Health and Environmental Effects Research You are here: EPA Home o Research & Development . National Health & Environmental Effects Research Laboratory » PFAA Days III Agenda PFAA Days III: Agenda Return to PFAA Days III Home I Download Agenda in PDF Format June 8-10, 2010 U.S. EPA, Research Triangle Park, NC Auditorium C-1 11 June 8, Tuesday 11:00 AM Registration 1:00 - 11:110 PM Introduction- Chris Lau, TAD, NHEERL, ORD 1:10 - 1:20 Welcoming Remarks - Kevin Telchman, ORD 1:20 - 1:30 Charges of Conference - Elaine Francis, US EPA - ----------- 1:30 - 5:20 PFAAs in the environment- SessionLeaders: Andy Lindstrom (US EPA) and Dorok Muir (Environment Canada) 1:30 - 2:15 What's new with PFAAs in the environment? - Scott Mabury (University of Toronto) 2:15 - 2:45 NHANES: PFAAs in US general population - Antonia Calafat (CDC) 2:45 - 3:05 Break 3:05 - 3:35 PFAA distribution in source water and their effective treatment technologies - Shure! Tanaka (Kyoto University) 3:35 - 4:05 PFAAs in wildlife worldwide - Robert I (Environment Canada) 4:05 - 5:30 Open Discussion Reception in Atrium, and/or Focus Group I meeting in Auditorium Focus Group 1: PFAA Analytical Chemistry - Group Leaders: Mark Strynar (US EPA), Shoji Nakayama (US EPA), David Ehresman (314), Mary Kaiser (DuPont) I c, discuss issues concerning the analysis of pernuorinated compounds: minis nun requirements elDents of quality assurance and quality control that make data acceptable. Topics will include assessment of accuracy and precision of a method, demonstration of data reliability at low 5:30 - 6:45 quantitalion levels, inclusion of method/matrix blanks, blank matrix spike recovery, use of common reference materials or standards for standardization of methods, potential sources of PFC contamination, and interlaboratery precision. In addition, other issues such as strengths and pitfalls of new analytical techniques (TOF/MS, ion chromatography, total fluorine measurement), ability to analyze a growing number of perfluorinated compounds (on-line SPE, high though -put), modification of analytical equipment for the application to PFC analysis (trap column, removal of LC components) will be addressed. 7:00 Dinner I (optional) at local restaurant June 9, Wednesday 7:45 - 8:20 AM Light breakfast and coffee 8:20 - 8:30 House -keeping - Lau 8:30 - noon PFAA exposure - Session Leaders: Laurence Libelo (US EPA) and Kerry Deerfield (USDA) 8:30 - 8:50 PFAAs in various environmental media - Mark Strynar (US EPA) 8:50 - 9:10 Environmental -Fate Patterns for PFAAs and their Precursors - John Washington (US EPA) 9:10 - 9:30 PFCs in Consumer Articles - Monitoring the Market Trends - Heidi Hubbard (US EPA) 9:30 - 9:50 Break 9:50 - 10:10 PFAAs in waste water treatment plants and sludge - James Kelly (Minnesota Department of Health) 10:10 - 10:30 PFAA exposure to farm cattle - Kerry Deerfield (USDA) 10:30 - 10:50 PFAAs infood and migration from food and packaging -Tim Begley (FDA) 10:50 - 12:00 Open Discussion Poster Session I in Atrium - Environmental PFAAs and Exposure Noon - 1:45 PM (boxed lunch provided) 1:45 - 5:30 PFAA epidemiology - Session Leaders: Andrea Pfahles-Hutchens (US EPA) and Geary Olson (3M) 1:45 2:00 A brief ovorviow of PFAA opiderniology - Geary Olsen (MA) The C8 Science Panel Program and findings from cross sectional analyses of C8 and clinical 2:00 - 2:25 markers in the Mid -Ohio Valley population - Tony Fletcher (London School of Hygiene and Tropical Medicine) 2:25 - 2:45 Retrospective Exposure Analysis and Predicted Serum Concentrations of PFOA in the Ohio River Valley - P. Barry Ryan (Emory University) 2:45 - 3:00 Open Discussion 3:00 - 3:20 Break 3:20 - 3:40 PFAAs and C8 study with Type 11 diabetes, uric acid, and lipids - Kyle Steenland (Emery University) 3:40 - 4:00 PFOA And Heart Disease: Epiderniologic Studies of Occupationally Exposed Populations - J. Morel Symons (DuPont) 4:00 - 4:25 Open Discussion on toxicological findings vs. epidemiological reports I oft 6/7/2010 9:25 AM DEQ-CFW-00000720 PFAA Days M Agenda I US EPA http://www.cpa.gov/nheorl/pfaa_days_3/agenda.litiiA PFAAs and reproductiveidevelopmental endpoints, pregnancy outcomes in C8 and other 4:25 — 4:45 community health studies, methodological considerations and future research — Cheryl Stein (Mount Sinai School of Medicine) 4:45 — 5:05 PFAAs and pregnancy outcomes in general population studies, methodological considerations, physiology of pregnancy considerations and future research — Matthew Longnecker (NIEHS) 5:05 — 5:30 Open Discussion Social Hour in Atrium, and/or Focus Group 11 meeting in Auditorium Focus Group 11: PFAA issues Among Governmental Agencies — Group Leaders: Andy Lindstrom (US EPA), Tony Krasnic (US EPA), Gail Mitchell (US EPA), Graham White (Health Canada) To provide an informal venue for networking among risk assessors and other specialists from various regulatory agencies in US (Regions, States, local) 5:30 - 6:45 and other countries concerning issues they currently face with PFAAs. Participants are invited to share their experience, questions and research needs relating to: PFAA sources, presence in environmental media, transport between and within media, relationships between various media (e.g. soil to water, surface water to drinking water); organizing environmental monitoring surveys; laboratory analysis options; commercial analytical services; development of toxicological end points for regulation and remediation, remediation approaches, health advisory levels; organizing comprehensive management policies; and emerging issues of interest. 7:00 Dinner II (optional) at local restaurant June 10, Thursday 7:45 -8:20 AM Light breakfast and coffee 8:20 - 8:30 House -keeping — Lau 8:30 - Noon PFAA toxicittes — Session Leaders: Jennifer Seed (1.1S EPA) and John Butenhoff (3M) 8:30 — 9:00 An overview of PFAA pharmacoldnatics — Harvey Clewell (Hamner Inolituto) 9:00 —9:30 Organic anion transporters and PFAA tissue distribution — Bruno Hagenbuch (Univeristy of Kansas) 9:30 — 9:50 Break 9:50 —10:20 An overview of PFAA toxicity — John Butenhoff (3M) 10:20 —10:50 PFAA ecotoxicity — John Newsted (Michigan Sate University) 10:50 —12:00 Open Discussion _ Noon -1:45 PM Poster Session li In Atrium — PFAA Toxicity, Modes of Action and Epidemiology (boxed lunch provided) 2:00 - 5:15 Nuclear receptor involvement in PFAA actions — Session Leaders: Chris Gorton (US EPA), Cliff Elcombe (CXR Bioscinnces) 1:45 —2:00 A brief overview of PFAA modes of action — Chris Carton (US EPA) 2:00 — 2:30 PPAR involvement in PFAA development toxicity — Barbara Abbott (US EPA) 2:30 —3:00 Nuclear receptor Involvement In PFAA-Induced metabolic changes— Mitch Rosen (US EPA) 3:00 — 3:20 Break 3:20 — 3:50 PPAR involvement in PFAA immunotoxicity —Jaime DeWitt (East Carolina University) 3:50 — 5:15 Open Discussion on PFAA toxicity and Modes of action, and their relevance to epidemiological findings 5:15 - 5:30 Closing remarks — Elaine Francis (US EPA) 5:30 Conference adjourned 2 of 2 6/7/2010 9:25 AM DEQ-CFW 00000721 Raleigh, Raleigh -Durham International Airport, and Points East via Interstate 40 Take Interstate 40 West toward Research Triangle Park, Durham, and Chapel Hill Take Exit 279A - to T.W. Alexander Drive and merge onto NC 147 South for 0.8 miles Proceed to T-intersection (stoplight) and turn left onto T.W. Alexander Drive Go 0.3 miles to the stoplight and turn left into the main entrance of the EPA-RTP Campus Visitors must stop at the Guard's station to show photo identification and get a parking pass Continue past the National Computer Center on the left as you come up the driveway and follow the signs to the Main Campus entrance and visitor's lot DEQ-CFW 00000722 P75. Hepatocellular Hypertrophy and Cell Proliferation in Sprague-Dawley Rats from Dietary Exposure to Potassium Perfluorooctanesulfonate Results from Increased Expression of Xenosensor Nuclear Receptors PPARa and CAR/PXR Clifford R. Elcombe1, Barbara M. Elcombel, John R. Foster2, Shu-Ching Chang 3, David J. Ehresman3, John L. Butenhoff3'* CXR Biosciences Ltd, Dundee DD1 5JJ, Scotland, UK; 2AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SKI 4TG, England, UK; 33M Company, St. Paul, MN, USA Perfluorooctanesulfonate (PFOS), a persistent and bioaccumulative fluorinated surfactant, produces hepatomegaly and hepatocellular hypertrophy in rodents. In mice, PFOS-induced hepatomegaly is associated with increased expression of the xenosensor nuclear receptors, PPARa and CAR/PXR. Although non-genotoxic, chronic dietary treatment of male and female Sprague-Dawley (S-D) rats with potassium PFOS (K+PFOS) produced an increase in hepatocellular tumors in males and females fed 20 ppm K+PFOS. In addition, male rats in the highest dose group of the latter study for whom dosing was suspended after one year had a. statistically significant increased incidence of thyroid follicular cell adenoma as compared to control males and highest dose males for whom dosing was not suspended after one year (stop -dose group). Although the etiological basis of the thyroid follicular tumors in the stop -dose group has remained recondite, hepatic activation of the peroxisome proliferator activated receptor a (PPARa) has been demonstrated in rats, suggesting a potential role for PPARa in the etiology of the hepatocellular tumors. The present study further investigates the potential role for K+PFOS-induced activation of PPARa in addition to potential activation of the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) with respect to liver tumor production in the S-D rat. The specific PPARa agonist, 4-chloro-6-(2,3- xylidino)-2-pyrimidinylthioacetic acid (Wy 14,643) and the specific CAR/PXR agonist, sodium Phenobarbital (PB), were included as positive controls. METHODS: Male S-D rats were fed potassium PFOS (20 or 100 ppm in diet), sodium Phenobarbital (500 ppm in diet) or Wy 14,643 (50 ppm in diet) for either 1, 7, or 28 days and sacrificed on either day 2, 7, or 29. Biochemical parameters assessed were: plasma ALT, AST, cholesterol, triglycerides, and glucose; liver protein and DNA content; liver activities of acyl CoA oxidase, Cyp4A, CYP213, and CYP3A; induction of liver CYP4A1, CYP2E1, CYP2131/2, and CYP3A1 proteins (SDS-PAGE and Western blots). Liver histological parameters assessed were: H&E staining observations; apoptotic index (TUNEL); cell proliferation index (BrdU S-phase incorporation). Concentrations of PFOS anion, PB, and Wy 14,643 were determined in serum, liver, and liver cytosol by LC-MS/MS methods. RESULTS: Terminal body weight at 29-day sacrifice was decreased by K+PFOS (100 ppm) and Wy 14643. K+PFOS (100 ppm) reduced food consumption beginning in the second week of the study. All test compound treatments increased liver weight (absolute and relative). Plasma ALT and AST values indicated a lack of overt DEQ-CFW 00000723 hepatotoxicity. Plasma cholesterol and triglycerides were decreased by both K+PFOS and Wy 14643. Glucose was reduced by K+PFOS after treatment for 28 days and by Wy 14,643 after 1 day only. After treatment for 1 day, K+PFOS (100 ppm), PB, and Wy 14643 increased mean hepatic DNA concentration and total DNA. Total DNA remained elevated after 7 days of treatment and 28 days of treatment (PB and Wy 14,643 only). Hepatic P450 concentration was elevated by both K+PFOS treatments and by PB. K+PFOS and Wy 14,643 treatment resulted in increased liver activities of palmitoyl CoA oxidase and CYP4A as well as increased liver CYP4A1 protein, and these enzyme activities were also elevated to a lesser extent by PB only after 7 days. K+PFOS and PB treatment increased liver activities of CYP213 and CYP3A as well as increased liver CYP2B1/2 and CYP3A1 proteins, and CYP2B enzyme activity was slightly elevated by Wy 14,643. All test compound treatments increased the liver cell proliferative index, and K+PFOS (100 ppm), PB, and Wy 14,643 decreased the liver apoptotic index. These data suggest that the hepatomegaly and tumors observed after chronic dietary exposure of S-D rats to K+PFOS likely are due to a proliferative response to combined activation of PPARa and CAR/PXR. This mode of action is unlikely to pose a human hepatocarcinogenic hazard. DEQ-CFW 00000724 U.S. EPA PFAA DAYS III SYMPOSIUM Barbara Abbott Principal Investigator EPA/ORD/NHEERUTAD 2525 E Hwy 54 Durham, NC 27713 919 541-2753 abbott.barbara@epa.gov Linda Aller Hydrogeologist Bennett & Williams 98 County Line Road West, Suite C Westerville, OH 43082 614-882-9122 x 135 laller@bennettandwilliams.com Roberta Altman EHS Manager PSL 1105 Sunnyfield Ct Dallas, NC 28034 7046890680 baltman@peachstatelabs.com PARTICIPANTS Barbara Beck Principal Gradient 20 University Rd, 5th Floor Cambridge, MA 02138 617-395-5000 bbeck@gradientcorp.com Arthur Beers Global Chemical Regulatory Manager OMNOVA Solutions Inc. 1455 J. A. Cochran Bypass Chester, SC 29706 803-377-2276 bill.beers@omnova.com Tim Begley Chief Methods Development Branch FDA 5100 Paint Branch Parkway College Park, MD 20740 301-436-1893 timothy.begley@FDA.hhs.gov Stacey Anderson Robert Bilott Associate Service Fellow Partner CDC/NIOSH Taft, Stettinius & Hollister, LLP 1095 Willowdale Dr 425 Walnut Street, Suite 1800 Morgantown, WV 26505 Cincinnati, OH 45202 304-285-6174 X 2 513-381-2838 dbx7@cdc.gov bilott@taftlaw.com James Andrews Heather Bischel Research Toxicologist Student EPA Stanford University MD 67, usepa 908 Middle Ave. Apt. J RTP, NC 27711 Menlo Park, CA 94025 919-541-2487 530-613-6696 andrews.james@epa.gov hbischel@stanford.edu Katherine Anitole Toxicologist EPA 1200 Penn Ave. NW MC 7403M Washington, DC 20460 202-564-7677 anitole.katherine@epa.gov Vannessa Barnes Laboratory Supervisor City of Raleigh P.O. Box 590 Raleigh, NC 27602 919-870-2870 vannessa.barnes@raleighnc.gov Scott Bartell Assistant Professor University of California, Irvine 2241 Bren Hall Irvine, CA 92697-1250 949.824.5984 sbartell@uci.edu Jack Bishop Research Geneticist/Staff Scientist NIEHS 530 Davis Drive, Keystone 2088 RTP, INC 27709 919-541-1876 bishop@nihes.nih.gov Chad Blystone Toxicologist NIEHS/NTP NIEHS/NTP, MD K2-12, PO BOX 12233 Research Triangle Park, NC 27709 919-541-2741 blystonecr@niehs.nih.gov Phillip Bost Student Services Contractor US-EPA/HEASD 1407 Acadia St Durham, NC 27701-1301 864 420 5644 philliposophy@gmail.com Connie Brower Industrial Hygiene Consultant State of North Carol ina,Division of Water Quality 1617 Mail Service Center Raleigh, NC 27699-1617 919-807-6416 connie.brower@ncdenr.gov Ann Brown Communications Director EPA 4930 Page Road, MD E205-09 Durham, NC 27703 919-541-7818 brown.ann@epa.gov Bob Buck Technical Fellow DuPont 4417 Lancaster Pike, BMP23-2236 Wilmington, DE 19803 302-892-8935 robert.c.buck@usa.dupont.com Gary Burleson President & CEO BRT-Burleson Research Technologies, Inc. 120 First Flight Lane Morrisville, NC 27560 919-719-2500 gburleson@brt-labs.com John Butenhoff Corporate Scientist 3M Company 3M Company, 3M Center, 220-6W-08 St. Paul, MN 55144 651-733-1962 jlbutenhoff@mmm.com Craig Butt Postdoctoral Researcher Duke University A150 Levine Science Research Center Durham, NC 27708 919-613-7472 craig.butt@duke.edu Yaqi Cai Professor RCEES, Chinese Academy of Sciences Shuangqing Road 18, Haidian District, Beijing 2871# Beijing, China, 100085 8610-62849239 caiyagi@rcees.ac.cn 77 DEQ-CFW 00000725 Antonia Calafat Division Chief CDC 4770 Buford Hwy, MS F-53 Atlanta, GA 30341 770-488-7891 acalafat@cdc.gov Miguel Cardona Sales and Marketing DuPont POBOX 80702 Wilmington, DE 19880-0702 302-999-3094 miguel.a.cardona@usa.dupont.com Leigh Carson Information Specialist and Research Scientist The Sapphire Group, Inc 3 Bethesda Metro Center, Suite 830 Bethesda, MD 20814 301-657-8008 ext 206 Ic@thesapphiregroup.com Sue Chang Toxicology Specialist 3M Company 3M Company, 3M Center, 220-6W-08 St. Paul, MN 55144 651-733-9073 s.chang@mmm.com Ian Chatwell Senior Environmental Officer Transport Canada 620 - 800 Burrard Street Vancouver, V6Z 2J8 604 666 6750 ian.chatwel I@tc.gc.ca Neil Chernoff Scientist EPA US Environmental Protection Agency Research Triangle Park, NC 27711 (919)541-2651 chernoff.neil@epa.gov Harvey Clewell The Hamner Institutes for Health Sciences 6 Davis Drive (PO Box 12137) Research Triangle Park, NC 27709 919-558-1211 hclewell@thehamner.org Perry Cohn Research Scientist NJ Dept Health and Senior Services PO Box 369 Trenton, NJ 08625-0369 609-826-4946 perry.cohn@doh.state.nj.us Chris Corton Senior Research Biologist US EPA 109 TW Alexander Drive Research Triangle Park, NC 27709 919-541-0092 corton.chris@epa.gov John Cosgrove President AXYS Analytical Services Ltd 2045 Mills Road West Sidney, V8L5X2 250 655 5800 josgrove@axys.com Jiayin Dai Professor Institute of Zoology, Chinese Academy of Sciences A319,Bei Chen Xi Lu 1-5, Chaoyang District Beijing, China, 100101 +80-(0)10-64807185 daijy@ioz.ac.cn Sally Darney National Program Director EPA US EPA, MD E205-09 Research Triangle Park, NC 27511 919-541-3826 darney.sally@epa.gov Selene Chou Kaberi Das Environmental Health Scientist Biologist Agency for Toxic Substances and Disease US EPA Registry 2525 E Hwy 54 1600 Clifton Road MS F62 Durham, NC 27713 Atlanta, GA 30033 919 541 3139 770-488-3357 das.kaberi@epa.gov cjc3@cdc.gov Jonathan Clapp Fluoropolymers Business Manager AGC Chemicals Americas, Inc. 55 East Uwchlan Ave. Suite 201 Exton, PA 19341-1204 jclapp@agcchem.com jclapp@agcchem.com Stephanie Davis Epidemiologist ATSDR 4770 Buford Highway NE MS F57 Atlanta, GA 30341 770-488-3676 SIDavis@cdc.gov 0 Amila De Silva Research Scientist Environment Canada 867 Lakeshore Road Burlington, ON, L7R 4A6 905-336-4407 amila.desilva@ec.gc.ca Patricia deLisio Sponsor Relationship Director MPI Research 952 Lander Rd Highland Hts, OH 44143 216-849-3463 patricia.delisio@mpiresearch.com Michael DeVito Toxicologist NIEHS 111 TW Alexander Drive, RTP, INC 27709 919-541-4142 devitom@niehs.nih.gov Jamie DeWitt Assistant Professor East Carolina University 600 Moye Blvd. Greenville, NC 27834 252.744.2474 dewittj@ecu.edu Darlene Dixon Head, Comparative Pathobiology Group NIEHS 111 TW Alexander Drive Research Triangle Park, NC 27709 (919) 541-3814 dixon@niehs.nih.gov Joyce Donohue Health Scientist EPA 1200 Pennsylvania Ave Mail Code 4304T Washington, DC 20460 202-566-1098 donohue.joyce@epa.gov Irene Dooley Environmental Scientist U.S. Environmental Protection Agency 1200 Pennsylvania Ave, NW (4607 M) Washington, DC 20460 (202)564-4699 dooley.irene@epa.gov Elizabeth Doyle Branch Chief USEPA/OW 1200 Pennsylvania Ave., NW Washington, DC 20460 202-566-0056 doyle.elizabeth@epa.gov DEQ-CFW 00000726 Alan Ducatman Adam Filgo Professor UNC/NIEHS WVU School of Medicine, Dept of 412 Lyons Rd. Community Medicine Chapel Hill, NC 27514 3907 Westlake Drive 619.917.2326 Morgantown, WV 26508 filgo@email.unc.edu 304 594-1336h 304 293-2502w aducatman Anna Fisher Team Leader, Genomlcs Research Core Jan Dye EPA Research Biologist RTP, NC 27711 USEPA/ NHEERL 919-541-4165 RTP, NC 27711 fisher.anna@epa.gov 919-541-0678 dye.janice@epa.gov Jocelyn Flanary Biologist/PhD Candidate David Ehresman National Institute of Standards and Sr. Toxicology Specialist Technology/Medical University of South 3M Company, 3M Center, 236-C148 Carolina St. Paul, MN 55144 331 Ft. Johnson Rd. 651-733-5070 Charleston, SC 29412 djehresman@mmm.com 843-762-8977 jocelyn.flanary@noaa.gov Cliff Elcombe Director Tony Fletcher CXR Biosciences Senior Lecturer James Lindsay Place, Dundee LSHTM Technopole Keppel St Dundee, Scotland, UK, DD15JJ London, UK, WV1 E 7HT 44-1382-432163 +44 207 927 2429 cliffelcombe@cxrbiosciences.com tony.fletcher@lshtm.ac.uk Jackson Ellington Roy Fortmann Research Chemist Acting Director EPA EPA/ORD/NERUHEASD 960 College Station RD MD E205-01, 109 TW Alexander Dr Athens, GA 30605 Research Triangle Park, NC 27711 706 355 8204 919-541-2454 ellington.jackson@epa.gov fortmann.roy@epa.gov Brian Englert Environmental Scientist EPA 1301 Constitution Avenue, Rm (Connecting Wing) Washington, DC 20004 202-566-0754 englert.brian@epa.gov Cathy Fehrenbacher Branch Chief EPA 1200 Pennsylvania Ave. N.W. Washington, DC 20460 202-564-8551 fehrenbacher.cathy@epa.gov Randy Frame Research Fellow and Manager, Pathology DuPont Haskell Global Centers 6231AA 1090 Elkton Road Neward, DE 19714 302-366-5169 steven.r.frame@usa.dupont.com Sue Fenton Reproductive Endocrinologist NIEHS/NTP 111 TW Alexander Dr., MD E1-08 Research Triangle Park, NC 27709 919-541-4141 fentonse@niehs.nih.gov Elaine Francis National Program Director for Pesticides and Toxics Research US Environmental Protection Agency 1200 Pennsylvania Avenue, NW (8101R) Washington, DC 20460 202-564-0928 francis.elaine@epa.gov Jennifer Franko Associate Service Fellow NIOSH 1095 Willowdale Rd m/s 4020 Morgantown, WV 26505 304-285-6174 x 8 hfy0@cdc.gov Alicia Fraser Boston University School of Public Health 715 Albany St, T4W Boston, MA 02118 617-638-8357 afraser@bu.edu Dori Germolec Immunology Discipline Leader NIEHS/NTP 530 Davis Drive Morrisville, NC 27560 919-541-3230 germolec@niehs.nih.gov Mary Gilbert Research Biologist US EPA 6 Sandhurst Durham, NC 27712 919 541-4394 gilbert.mary@epa.gov Robert Giraud Senior Consultant DuPont Company 1007 Market Street Wilmington, DE 19898 3027748048 robert.j.giraud@usa.dupont.com Dana Glass Toxicologist/veterinarian Oak Ridge National Laboratory 545 Oak Ridge Turnpike Oak Ridge, TN 37830 865-241-3202 glassd@ornl.gov Helen Goeden Research Scientist MN Department of Health 625 Robert Street N St. Paul, MN 55164 651-201-4904 helen.goeden@state.mn.us Rocky Goldsmith US EPA 109 TW Alexander Drive Research Triangle Park, NC 27709 919-541-0497 Curtis Grace Biologist US EPA 136 Westover Hills Dr. Cary, NC 27513 9195410852 grace.curtis@epa.gov David Gray Toxicologist Independent Consultant 7057 Western Ave Washington, DC 20015 202 380 3692 david.gray2@comcast.net 79 DEQ-CFW 00000727 Mark A. Greenwood Wendy Heiserman Gary Hohenstein Ropes & Gray LLP ORISE Chemist Manager, Environmental & Regulatory One Metro Center, 700 12th Street, FDA Affairs Suite 900 5100 Paint Branch Pkwy 3M Company Wasington, DC 20005-3948 College Park, MD 20740 3M Center, Bldg 224-5W-03 1-202-508-4605 301-436-1971 St. Paul, MN 55144-1000 mgreenwood@ropesgray.com wendy.heiserman@fda.hhs.gov 651737-3570 gahohenstein@mmm.com Brian Grey David Herr Biologist Chief, Neurotoxicology Branch Angela Howard DTB/TAD/NHEERL/ORD/US EPA US EPA Toxicologist 109 TW Alexander Drive MD-67 MD B105-05, NHEERL/TAD, 109 TW EPA RTP, NC 27711 Alexander Dr. MC 7403M 1200 Pennsylvania Ave, N.W. 919-541-1055 Durham, NC 27711 Washington, DC 20460 grey. brian@epa.gov 919-541-0380 202-564-9867 Herr.david@epamail.epa.gov howard.angela@epa.gov Bob Griffin General Manager Robert Herrick Heidi Hubbard Little Hocking Water Association Graduate Student Physical Scientist P.O. Box 188 University of Cincinnati EPA Little Hocking, OH 45742 207 Bradstreet Rd 109 TW Alexander Dr. 740-989-2181 Centerville, OH 45459 Durham, NC 27711 lhwater@roadrunner.com 513-558-1912 919-541-5571 herricrl@mail.uc.edu hubbard.heidi@epa.gov Bruno Hagenbuch Professor Susan Hester Ronald Hunter The University of Kansas Medical Center Biologist Environmental Health Fellow 3901 Rainbow Blvd. US EPA EPA Kansas City, KS 66160 109 Alexander Dr PO Box 4114 (913) 588-0028 Durham, NC 27711 Washington, DC 20044 bhagenbuch@kumc.edu 919-541-1320 404-200-8511 hester.susan@epa.gov hunter.ronald@epa.gov Coreen Hamilton Axys Analytical Services Ltd. Christopher Higgins Juergen Hoelzer 2045 Mills Rd Assistant Professor, Environmental Medical Scientist Sidney, BC, canada, V8L 5X2 Science and Engineering Division Ruhr -University Bochum, Department for 250-655-5802 Colorado School of Mines Hygiene, Social and Environmental chamilton@axys.com 1500 Illinois Street Medicine Golden, CO 80401 MA 1/33,Universitaetsstrasse 150 Kerry Hamilton 720-984-2116 Bochum, 44801 ASPH Public Health Fellow chiggins@mines.edu 00 49 234 3226994 EPA juergen.hoelzer@rub.de 1862 Mintwood PI NW Apt 404 Ross Highsmith Washington, DC 20009 ALD for Pesticides/Toxics Sean Ireland 5165573772 US EPA, ORD/NERL Environmental Engineer hamilton.kerry@epa.gov 919-541-7828 EPA highsmith.ross@epa.gov 1470 Hardee St Kimberly Harris Atlanta, GA 30307 Life Scientist Erin Hines 404-562-9776 EPA -Region 5 Biologist ireland.sean@epa.gov 77 W. Jackson Boulevard EPA Chicago, IL 60604 US EPA, B243-01 Hiroyuki Iwai 312-886-4239 RPT, NC 27711 D.V.M, Toxicology & Product Regulatory harris.kimberiy@epa.gov 9195414204 Daikin Industries, Ltd. hines.erin@epa.gov 1-1 Nishi Hitotsuya, Andrew Hartten Settsu-City, Osaka, Japan, 566-8585 Project Director/Consultant Kate Hoffman 81-6-6349-5336 DuPont Company Boston University hiroyuki.iwai@daikin.co.jp DuPont Chestnut Run Plaza 715 Albany St; Talbot 4W Wilmington, DE 19805 Boston, MA 02118 Jyotsna Jagai 302-999-6197 812-599-4459 Postdoctoral Fellow andrew.s.hartten@usa.dupont.com kate.hoffman.scharf@gmail.com EPA U.S. EPA, MD 58A Line Smastuen Haug Research Triangle Park, NC 27711 PhD student 919-966-6209 Norwegian Institute of Public Health jagai.jyotsna@epa.gov P.O.Box 4404 Nydalen Oslo, Norway, 0403 +47 21076549 line.smastuen.haug@fhi.no DEQ-CFW 00000728 Jean Johnson Epidemiologist Minnesota Department of Health 85 East Seventh Place, Suite 220 St. Paul, MN 55164 651-484-0583 jean.johnson@state.mn.us Reg Jordan Industrial Hygiene Consultant NC Division of Air Quality 1641 Mail Service Center Raleigh, NC 27699-1641 9197331475 reginald.jordan@ncdenr.gov Reinhard Jung Toxicologist Clariant c/o 4000 Monroe Road Charlotte, NC 28205 49 6196 757 8778 reinhard.jung@clariant.com Mary A Kaiser Sr. Research Fellow DuPont P.O. Box 80402 Wilmington, DE 19880-0402 302-695-8435 mary.a.kaiser@usa.dupont.com James Kelly Research Scientist MN Department of Health 625 N. Robert Street St. Paul, MN 55164-0975 651-201-4910 james.kelly@state.mn.us Gerald Kennedy Contractor -Risk Assessment DuPont Company 17 Benton Court Wilmington, DE 19810 302-999-4759 gerald.kennedy@usa.dupont.com Todd Kennedy Toxicologist W L Gore & Associates 4100 W Kiltie Ln Flagstaff, AZ 86001 928-864-3380 tkennedy@wigore.com Sung Jae Kim Biologist EPA 2525 E. Hwy 54 RTP, NC 27711 919-541-2114 kim.sung-jae@epa.gov Kirk Kitchin Research Toxicologist US EPA MD B143-06 109 Alexander Drive, RTP, NC 27711 541-7502 kitchin.kirk@epa.gov James E. Klaunig Robert B. Forney Professor of Toxicology Indiana University School of Medicine 541 Clinical Drive, Room 591 Indianapolis, IN 46202 317-274-7824 jklauni@iupui.edu Detlef Knappe Professor NC State University, CB 7908 Raleigh, NC 27695-7908 919-515-8791 knappe@ncsu.edu Wolfgang Knaup �-;R&D Textile Chemicals Clariant c/o 4000 Monroe Road Charlotte, NC 28205 49 8679/7-4653 wolfgang.knaup@clariant.com Thomas Knudsen Developmental Systems Biologist EPA NCCT Research Trangle Park, NC 27711 919-541-9776 knudsen.thomas@epa.gov Volker Koch Product Safety Toxicology - Environmental Safety Assessment Clariant c/o 4000 Monroe Road Charlotte, NC 28205 49 6196 757 7343 volker.koch@clariant.com Stephen Korzeniowski Global Technology Manager DuPont Route 141 & Henry Clay Wilmington, DE 19880-0402 1-302-695-8672 stephen.h.korzeniowski@usa.dupont.com Toni Krasnic Chemist EPA 1200 Pennsylvania Ave NW; MC 7405M Washington, DC 20460 2025640984 krasnic.toni@epa.gov Ken Krebs Chemist EPA E305-03 RTP, NC 27711 919 541-2850 krebs.ken@eop.gov Jessy Kurias Senior Evaluator/Challenge Coordinator Environment Canada 200 Sacre-Coeur Blvd Ottawa, Ontario, K1A OH3 819-934-4210 Jessy.Kurias@ec.gc.ca Anna Karrman Lecturer MTM Research Centre, Orebro University 701 82 Orebro, Sweden, +4619301401 anna.karrman@oru.se Susan Laessig Toxicologist EPA 1200 Pennsylvania Ave, 7405M Washington, DC 20460 202-564-5232 laessig.susan@epa.gov David Lai Senior Toxicologist EPA 1200 Pennsylvania Ave., N.W. Washington, DC 20460 202-564-7667 lai.david@epa.gov Edward Lampert Lampert&Associates 3-15-11-940 Roppongi, Minato-ku Tokyo, Japan, 106-0032 1-917-365-4440 lampert@lampert-japan.com Christopher Lau Acting Branch Chief EPA MD-67, US Environmental Protection Agency Research Triangle Park, NC 27711 919-541-5097 lau.christopher@epa.gov Susan Laws Research Biologist. U.S. EPA 2525 HWY 54 Durham, NC 27713 919 541-0173 laws.susan@epa.gov Holly Lee Graduate Student University of Toronto 80 St. George Street Toronto, M5S 31­16 416-946-7736 hlee@chem.utoronto.ca DEQ-CFW 00000729 Robert Letcher Research Scientist / Adjunct Professor Environment Canada 1125 Colonel By Dr., National Wildlife Research Centre, Bldg. 33, Carleton University Ottawa, Ontario, Canada, K1A OH3 613-998-6696 robert.letcher@ec.gc.ca Carol Ley Director Occupational Medicine 3M 3M Building 220-6W-08 St. Paul, MN 55047 651-733-0694 caley@mmm.com Laurence Libelo Senior Environmental Engineer EPA 1200 Penn. Ave., NW, MS 7406M Washington, DC 20460 202-564-8553 libelo.laurence@epa.gov Andrew Lindstrom Senior Research Chemist USFPA RTP, NC 27711 919-541-0551 lindstrom.andrew@epa.gov Robert Lippincott Research Scientist NJDEP Office of Science 183 Simons Drive Yardley, PA 19067 1-(609) 984-4699 lee. lippincott@dep.state. nj. us Xiaoyu Liu Physical Scientist US EPA 109 T.W. Alexander Dr. Durham, NC 27713 919-541-2459 liu.xiaoyu@epa.gov Anne Loccisano Postdoctoral Fellow The Hamner Institutes for Health Sciences 6 Davis Drive PO Box 12137 Research Triangle Park, NC 27709 919-558-1392 ALoccisano@thehamner.org Matt Longnecker Senior Investigator NIEHS MD A3-05 PO Box 12233 Durham, NC 27709 919 541-5118 longnecl@niehs.nih.gov Maria-Jnse Lopez -Espinosa London School of Hygiene and Tropical Medicine Camden High Street 2 Flat 154-156 London, NW1 ONE 004407530798209 Maria-Jose.Lopez@lshtm.ac.uk Judy Louis Bureau Chief —NJ Dept. of Environmental Protection PO Box 420 Trenton, NJ 08625 609-984-3889 judy.louis@dep.state.nj.us Bob Luebke Senior Research Biologist EPA MD B143-01 RTP, NC 27711 919.541.3672 luebke.robert@epa.gov William Luksemburg President Vista Analytical Laboratory 1104 Windfield Way EI Dorado Hills, CA 95762 9166731520 billux@vista-analytical.com Mike Luster Adjunct Professor West Virginia University 39 Quail Rd Morgantown, WV 26508 304-216-5516 miklus22@comcast.net Christopher Lyu Associate Director Battelle 100 Capitola Drive, Suite 200 Durham, NC 27713 (919) 544-3717 ext. 117 lyuc@battelle.org Scott Mabury Professor and Vice -Provost Academic Operations University of Toronto Department of Chemistry Toronto, M5S 3H6 416 978-2031 smabury@chem.utoronto.ca Laura MacManus-spencer Assistant Professor 840 DeCamp Ave. Schenectady, NY 12309 (518) 388-6153 macmanul@union.edu Denise MacMillan Analytical Chemistry Research Core Team Leader EPA/ORD/NHEERL/RCU 109 TW Alexander Dr RTP, NC 27711 (919)541-4128 macmillan.denise@epa.gov Madisa Macon Graduate Research Assistant University of North Carolina- Chapel Hill 635 Windsong Ln Durham, NC 27713 919-541-4703 madisa.macon@nih.gov Amal Mahfouz Senior Toxicologist Environmental Protection Agency - HQ; Office of Water EPA/OW (MC 4304-T), 1200 Pennsylvania Ave, NW, Washington, DC 20460 202-566-1114 mahfouz.amal@epa.gov Marie Martinko Dir. Industry Affair-. - Environment & Health SPI: The Plastics Industry Trade Association 1667 K Street NW, Suite 1000 Washington, DC 20006-1620 202-974-5330 mmartinko@plasticsindustry.org Mary McCoy Product Steward BASF Corporation 4330 Chesapeake Drive Charolotte, NC 28216 704-398-4262 mary.mccoy@basf.com Larry McMillan SEE -EPA 109 TW Alexander Drive RTP, NC 24409 919-541-5657 mcmillan.larry-rtp@epa.gov David Menotti Attorney `""'Pillsbury Winthrop Shaw Pittman LLP 2300 N Street, NW Washington, DC 20037 202-663-8675 david.menotti@pillsburylaw.com Larry Michael Research Scientist RTI International P.O. Box 12194 Research Triangle Park, NC 27709 919-541-6150 Icm@rti.org DEQ-CFW 00000730 William Mills President Mills Consulting Inc. 1010 lake st. ste 402 Oak Park, IL 60301 708 524-2166 wmills@mills-consulting.com Gail Mitchell Deputy Division Director EPA 61 Forsyth Street SW, 15th floor Atlanta, GA 30303 404-562-9234 or404-562-9837 mitchell.gail@epa.gov Debapriya Mondal London School of Hygiene and Tropical Medicine 56 Charteris Road London, UK, N4 3AB 07530798209 devmondaluk@yahoo.co.uk Alicia Moore Biologist NIEHS 111 TW Alexander Drive Research Triangle Park, NC 27709 (919) 541-7914 moore5@niehs.nih.gov Sandra Moore Environmental Toxicologist NC DENR DWQ 1617 Mail Service Center Raleigh, NC 27699-1617 919-807-6417 sandra.moore@ncdenr.gov Ginger Moser Toxicologist EPA MD 105-04 RTP, NC 27711 919-541-5075 moser.ginger@epa.gov Sandi Moser Controls Development Engineer Environment Canada 351 St. Joseph Blvd., 17th Floor Gatineau, Quebec, Canada, K1A OH3 819-953-2335 sand i.moser@ec.gc. ca Derek Muir Chief Aquatic Ecosystem Protection Research Division, Environment Canada Environment Canada Burlington, Ontario Canada, L7R 4A6 905-319-6921 derek.muir@ec.gc.ca Jonathan Naile Graduate Student University of Saskatchewan 311-215 Lowe Rd Saskatoon, S7S1N1 306-270-2139 jonathan.naile@usask.ca Takayuki Nakamura Daikin Industries, Ltd. Umeda Center Bldg. 2-4-12 Nakazaki- Nishi Osaka, Japan, 530-8323 81-6-6373-4347 takayuki.nakamura@daikin.co.jp Shoji Nakayama Researcher EPA/NRMRL 26 W Martin Luther King Dr Cincinnati, OH 45268 (513) 569-7490 nakayama.shoji@epa.gov John Newsted Senior Project Manager Entrix, Inc. 4295 Okemos Road Okemos, MI 48864 517-381-1434 jnewsted@entrix.com Tetsuji Nishimura Director National Institute of Health Sciences 1-18-1, Kamiyoga, Setagaya-ku Tokyo,158-8501 +81-3-3700-9291 nishimur@nihs.go.jp Yukiko Nishiyama Lampert&Associates 3-15-11-940 Roppongi, Minato-ku Tokyo, Japan, 106-0032 81-3-5562-9475 yukiko.nishiyama@Lmpert-japan.com Edward Ohanian Associate Director for Science EPA/Office of Water 1200 Penn. Ave. NW (MC:4301T) Washington, DC 20460 202-566-1117 ohanian.edward@epa.gov Fardin Oliaei Consultant 1801 Buttonwood St. Apt. 1002 Philadelphia, PA 19130 651-307-0483 fardino@gmail.com Geary Olsen Staff Scientist 3M Company, Medical Dept., Mail Stop 220-6W-08 St. Paul, MN 55144 651-737-8569 gwolsen@mmm.com Prajakta Palkar Postdoctoral Fellow Pennsylvania State University 302 Life Sciences Bldg State College, PA 16802 814-865-7174 psp11 @psu.edu June -Woo Park University of Tennessee 8822 Fox River Way Knoxville, TN 37923 jpark4l@utk.edu Andrew Patterson Scientist Vista Analytical Laboratory 1104 Windfield Way El Dorado Hills, CA 95762 916-673-1520 anp@vista-analytical.com Elizabeth Perill Publisher Elsevier 360 Park Avenue South New York, NY 10010 2126333833 e.perill@elseveir.com Terry Peters Sr. Dir. Technical and Industry Affairs SPI 1667 K Street NW, Ste. 1000 Washington, DC 20006 202-974-5280 tpeters@plasticsindustry.org Andrea Pfahles-Hutchens Epidemiologist EPA 1200 Pennsylvania Ave., NW, 7403M Washington, DC 20460 202-564-7601 pfahles-hutchens.andrea@epa.gov Daniel Pigeon W.L. Gore and Associates P.O. Box 1220 Elkton, MD 21922-1220 410-506-2173 dpigeon@wlgore.com Susan Pinney Associate Professor U of Cincinnati College of Medicine UC PO Box 670056 Cincinnati, OH 45267-0056 513-558-0684 susan.pinney@uc.edu Gloria Post Research Scientist --NJ Dept. of Environmental Protection PO Box 420 Trenton, NJ 08625 609-292-8497 gloria.post@dep.state. nj.us DEQ-CFW 00000731 Katherine Raleigh Graduate Research Assistant U of MN, School of Public Health 4347 Blaisdell Ave. S. Minneapolis, MN 55409 612-298-0843 koeh0003@umn.edu Ram Ramabhadran Division Director (Acting) EPA 919-541-3558 rariiab[iadran.ram@epa.gov Amy Rand Graduate Student University of Toronto 91 Edwin ave. Toronto Ontario, M6P 3Z5 416-946-7736 arand@chem. utoronto.ca Keegan Rankin Graduate Student University of Toronto 110 Peppertree Drive Mebane, NC 27302 416-978-3596 krankin@c-.hem. utoronto.ca Brenda Rashleigh Research Chemist EPA/ORD/NERL 960 College Station Road Athens, GA 30605 706-355-8148 rashleigh.brenda@epa.gov James Raymer Senior Research Chemist TI International 3040 Cornwallis Road RTP, NC 27709 919-541-5924 jraymer@rti.org Jennifer Rayner Toxicologist Oak Ridge National Laboratory 1060 Commerce Park Dr Oak Ridge, TN 37830 (865)574-6425 raynerjl@ornl.gov William Reagen Laboratory Manager 3M 3M Center, Bidg 260-05-N-17 St Paul, MN 55144-1000 651-733-9739 wkreagen@mmm.com Eric Reiner Mass Spectrometry Research Scientist Ontario Ministry of the Environment 125 Resoruces Road Toronto, M9P 3V6 416 235 5748 Eric. Reiner@Ontario.ca Jessica Reiner Research Chemist NIST 331 Fort Johnson Rd Charleston, SC 29412 843-725-4834 jessica.reiner@nist.gov Hongzu Ren Research Scientist US EPA 109 TW Alexander Drive Research Triangle Park, NC 27709 919-541-4576 ren.hongzu@epa.gov Kurt Rhoads Postdoctoral Associate Cornell University Dept of Civil & Environmental Engineering 466 Hollister Hall Ithaca, NY 14853 6507995680 kurtrhoads@gmail.com John Rogers Acting Director, TAD EPA MD-71, USEPA Research Triangle Park, NC 27711 (919)541-5177 rogers.john@epa.gov Joe Romano Senior Manager Waters Corporation 34 Maple Street Milford, MA 02333 508-482-2963 joe_romano@waters.com Mitchell Rosen Research Biologist EPA U.S. EPA, MD72 Research Triangle Park, NC 27711 919-541-2223 rosen.mitch@epa.gov Kenneth Rudo Kathy Rhyne State Toxicologist King & Spalding LLP NC Division of Public Health 1700 Pennsylvania Ave. NW 1005 Brendan Ct. Washington, DC 20006-4706 Chapel Hill, NC 27516 202-626-3743 9197075911 krhyne@kslaw.com krudo@earthlink.net Penelope Rice Erin Russell Toxicology Reviewer Asst. Gen. Counsel FDA/CFSAN/OFAS/DFCN Clariant Corporation 5100 Paint Branch Parkway 4000 Monroe Road College Park, MD 20740 Charlotte, NC 29205 301-436-1236 704-331-7059 penelope.rice@fda.hhs.gov erin.russell@clariant.com Robert Rickard Barry Ryan Distinguished Scientist DuPontZont Professor Department of Environmental Health, CRP 708/111 Rollins School of Public Health of Emory Wilmington, DE 19805 University 302 999-5315 1518 Clifton Road robert.w.rickard@usa.dupont.com Atlanta, GA 30322 404-727-3826 Connie Roberts bryan@emory.edu Special Assitant to the Director EPA Norirnitsu Saito 61 Forsyth Street Director Atlanta, GA 30303 RIEP of Iwate Prefecture 404-562-9406 liokashindn 1-36-1 roberts.connie@epa.gov Morioka, 020-0852 81-19-656-5666 Shona Robinson norimi@zpost.plala.or.jp Graduate Student University of Toronto Dina Schreinemachers 88 Spadina Rd (#509N) Health Scientisi Toronto, ON, M5R 2S8 EPA 647-678-9776 2606 Vinca Lane srobinso@chem.utoronto.ca Mebane, NC 27302 919-966-5875 schreinemachers.dina@epa.gov :2 DEQ-CFW 00000732 Christoph Schulte Seiji Shin-ya Adam Swank German Federal Environment Agency General Principal Specialist Chemist Worlitzer Platz 1 Asahi Glass Co., Ltd. EPA Desssau, D-06844 10 Goikaigan US EPA, MD: D305-02 +49 340 21033162 Ichuhara-shi, Chiba 290-8566 Japan, RTP, NC 27711 christoph.schulte@uba.de 81-436-23-3871 919-541-0614 seiji-shinya@agc.co.jp swank.adam@epa.gov Jay Schulz Sr. Product Steward Hyeong-Moo Shin J. Morel Symons 3M Company University of California -Irvine Supervisor 3M Center Bldg 236-1B-10 6306 Adobe Circle Rd E.1 du Pont de Nemours and Company St. Paul, MN 55144-1000 Irvine, CA 92617 1090 Elkton Road, Building S320/113 651-733-5463 9496481614 Newark, DE 19711-0357 jfschulz@mmm.com hyeongs@uci.edu 302-366-5305 J-Morel.Symons@usa.dupont.com Jennifer Seed Laura Solem Deputy Division Director Toxicologist Shuhei Tanaka EPA Minnesota Pollution Control Agency Associate Professor 1200 Pennsylvania Ave NW - mailcode 525 Lake Ave South, Suite 400 Kyoto University 7403M Duluth, MN 55802 Yoshida Honmachi, Sakyo-ku Washington, DC 20460 218-302-6628 Kyoto, Japan, 606-8501 202-564-7634 laura.solem@state.mn.us 81-75-753-5171 seed.jennifer@epa.gov t-shuhei@eden.env.kyoto-u.ac.jp Jason Stanko Brenda Seidman Biologist Katoria Tatum -Gibbs Toxicologist NIEHS Postdoctoral Fellow EPA 111 T.W. Alexander Dr. EPA 6625 Gordon Avenue RTP, NC 27709 4602 Coral Dr. Falls Church, VA 22046-1824 919-541-0461 Durham, NC 27713 202-564-4782 stankojp@niehs.nih.gov 919-541-5194 seidman.brenda@epa.gov tatum.katoria@epa.gov Heather Stapleton MaryJane Selgrade Assistant Professor Kevin Teichman Branch Chief Duke University Deputy Assistant Administrator for EPA LSRC, Box 90328 Science U.S. EPA, MD B-143 Durham, NC 27708 US Environmental Protection Agency Research Triangle Park, NC 27711 919-613-8717 1200 Pennsylvania Ave, NW 919-541-1821 heather.stapleton@duke.edu Washington, DC 20004 selgrade.maryjane@epa.gov 202-564-6620 Kyle Steenland teichman.kevin@epa.gov Tessa Serex Professor Senior Research Toxicologist Emory University Lee Thomas /- DuPont Haskell Global Centers for Health 1518 Clifton Rd. Hydrologist and Environmental Sciences Atlanta, GA 30322 EPA Region 4 54 Rose Hill Dr 404 712 8277 61 Forsyth Street Bear, DE 19701 nsteenl@sph.emory.edu Atlanta, GA 30303 302-366-5287 404 562 9786 tessa.l.serex@usa.dupont.com Cheryl Stein thomas.lee@epa.gov Instructor Yasuyuki Shibata Mount Sinai School of Medicine Shuji Tsuda National Institute for Environmental One Gustave L. Levy Place, Box 1057 Professor Studies New York, NY 10029 Iwate University 16-2 Onogawa 212-824-7083 Ueda 3-18-8 Tsukuba, Ibaraki, Japan, 305-8506 cheryl.stein@mssm.edu Morioka, 020-8550 81-29-850-2450 81-19-621-6981 yshibata@nies.go.jp Mark Strynar s.tsuda@iwate-u.ac.jp Physical Scientist Naoto Shimizu U.S. EPA Beena Vallanat Enginner 109 T.W. ALexander Dr. Research Scientist Agilent Technologies Durham, NC 27711 US EPA 9-1, Takakura-cho 919-541-3706 109 TW Alexander Drive Hachiouji-shi, Tokyo, strynar.mark@epa.gov Research Triangle Park, NC 27709 81-42-660-9920 919-541-2163 naoto_shimizu@agilent.com William Studabaker vallanat.beena@epa.gov Scientist RTI International Veronica Vieira Raleigh, NC 27612 113 Chandler St #2 919-541-8046 Boston, MA 02116 wstudabaker@rti.org 508-878-0126 vmv@bu.edu 85 DEQ-CFW 00000733 Robert Voyksner John Washington Douglas Wolf President Research Chemist Assistant Laboratory Director LCMS Limited EPA/ORD/NERL/ERD/PMB U. S. EPA PO Box 27228 960 College Station Road 109 TW Alexander, MD B305-02 Raleigh, NC 27611 Athens, GA 30605 Research Triangle Park, NC 27511 919-201-0047 706 355 8227 919-541-4137 robert_voyksner@lcroslimited.com washington.john@epa.gov wolf.doug@epa.gov Kristina Walker John Wathen Carmen Wood Postdoctoral Fellow Ass't. Branch Chief Biologist NIEHS EPA-OW-OST EPA 111 TW Alexander Drive 1200 Pennsylvania Ave., NW MD 72 Durham, NC 27709 Washington, DC 20460 RTP, NC 27711 919-541-7551 202-566-0367 919-541-2360 whitworthkw@niehs.nih.gov wathen.john@epa.gov wood.carmen@epa.gov Elizabeth Wallace Andrew Watkins Dan Wright Student Volunteer Biologist Director Analytical Sciences NIEHS EPA MPI Research 111 TW Alexander Drive 2525 NC Hwy 54 161 Meadowview Drive Research Triangle Park, NC 27709 RTP, NC 27713 State College, PA 16801 (919) 541-7914 919-541-7940 814-272-1039 moore5@niehs.nih.gov watkins.andrew@epa.gov dkpmwrlght@comcast.net Michele Wallace Stephen Watkins Muqi Xu Associate Director Physical Scientist Professor Cotton Incorporated EPA Institute of Zoology, Chinese Acedemy of 6399 Weston Parkway 1200 Pennsylvania Avenue, NW Sciences Cary, NC: 27513 Washington, DC 20460 Bei Chen Xi 1 1 1 1-5 Chaoyang v 919-678-2417 (202) 564-3744 District, Beijing, P.R. mwallace@cottoninc.com watkins.stephen@epa.gov Beijing, China, 100101 +80-(0)10-64807169 Teresa Wall Thomas Webster xumq@ioz.ac.cn Program Analyst Associate Professor and Assocaite Chair US EPA, ORD, NHEERL, TAD/10 Boston University School of Public Health, Mitsuha Yoshikane 1307 Walnut St., Lot 30 Dept. Environmental Health National Institute for Environmental Cary, NC 27713 715 Albany St Studies 919 541-3591 Boston, MA 02118 16-2 Onogawa wall.teresa@epa.gov (617)638-4620 Tsukuba,lbaraki,Japan, 305-8506 twebster@bu.edu 029-850-2668 John Wambaugh yoshikane.mitsuha@nies.go.jp Physical Scientist Graham White US EPA / NCCT Health Canada Dan Zehr 109 T.W. Alexander Dr. Mail Code B205-1 31 Marielle Court Chemist Research Triangle Park, NC 27711 Ottawa, Canada, K2B 8P2 EPA 919-541-7641 613-946-2312 109 TW Alexander Dr wambaugh.john@epa.gov graham.white@hc-sc.gc.ca RTP, NC 27709 919-541-1507 Jianshe Wang Al Wiedow zehr.dan@epamail.epa.gov PhD Candidate Senior Toxicologist Institute of Zoology, Chinese Academy of BASF Corporation Hongxia Zhang Sciences 100 Campus drive PhD A319, Bei Chen Xi Lu 1-5, Chaoyang Florham Park, NJ 07932 Institute of Zoology, Chinese Academy of District, Beijing, P.R. 203-798-0165 Sciences Beijing, China, 100101 al.wiedow@basf.com A319,Bei Chen Xi Lu 1-5, Chaoyang +80-(0)10-64807057 District jianshewang@126.com Andrea Winquist Beijing, 100101 Epidemiologist 086-10-6480700-7 Yawei Wang Emory University zhanghx@ioz.ac.cn Professor 1518 Clifton Road, NE RCEES, Chinese Academy of Sciences Atlanta, GA 30322 Larry Zobel Shuangqing Road 18, Haidian District, 404-727-3601 Vice President & Medical Director Beijing 2871# awinqui@emory.edu 3M Beijing, China, 100085 3M Medical Dept, Bldg. 220-6W-08 8610-62849339 Cynthia Wolf St. Paul, MN 55144-1000 ywwang@rcees.ac.cn Biologist 651-733-5181 EPA Izobel@mmm.com RTP, NC 919-541-5195 wolf.cynthiaj@epa.gov DEQ-CFW 00000734 Robert Zucker Research Biologist USEPA MD 67 RTP, NC 27711 919-541-1585 zucker.robert@epa.gov 87 DEQ-CFW 00000735