DEQ-CFW_00000858

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EPA
United States
Environmental Protection
Agency
14110
Sponsored by the Office of
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Recent Advances in
� Perfluoroaikyl Acid (PFAA) Research
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June 3-4, 2008
Open to the Public
June 5, 2008
EPA staff only
U.S. EPA - Research Triangle Park
Auditorium C-111
109 T.W. Alexander Drive
--- Research Triangle Park, N.C. 27711
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Background
The Perfluoroalkyl Acids (PFAAs), such as perflurooctanoic acid (PFOA)
and perfluorooctane sulfonate (PFOS), are persistent environmental
pollutants that are 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) of US EPA has been actively involved in the
assessment of these chemicals, as well as potential replacements for PFOS
and PFOA. In 2006, a draft human health risk assessment of PFOA
(http://www.epa.gov/opptintr/pfoa/index.htm) was reviewed by the
Agency's Science Advisory Board, and their report was released in May
(http://yosemite.epa. gov%sab/SABPRODUCT.NSF/A3C83 648E7725282852
5717F004139099/$File/sab_06_006.pdf). It identified several informational
gaps and recommended areas of critical research needs.
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), and more recently, from the
National Exposure Research Laboratory (NERL) and the National Risk
Management Research Laboratory (NRMRL) have developed research
programs to characterize the toxicity of these chemicals, to explore their
anodes of actions, to develop analytical methods for their detection in
various media, and to investigate the fate and transport of these chemicals in
the environment. Collectively, they are making significant strides in these
research areas.
In the summer of 2006, a "PFAA Days" workshop was held at the US EPA
ORD's facility in Research Triangle Park, NC where scientists and managers
from the Office of Prevention, Pesticides, and Toxic Substances (OPPTS),
the Office of Water (OW), the EPA Regions, and various offices and
laboratories within ORD assembled to learn of the research plans and
activities of investigators in NHEERL, NERL and NRMRL, to exchange
perspectives, and to identify research needs for risk assessment. The
workshop was highly successful, in that valuable insights were gained by all
participants.
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Goals and Lo,-istics
Since that workshop, significant research progress has been made by ORD
and other scientists, and different scientific issues concerning PFAAs have
emerged. It is, therefore, an appropriate time to hold another workshop,
PFAA Days II, to review the progress, to share the recent discoveries, to
address the current issues and to chart the future course for PFAA research
at ORD. This informal workshop is open to scientists from other federal and
state agencies, the chemical industry and academia for the sessions on June 3
and 4. Several prominent and active investigators working on exposure and
toxicity issues of PFAAs have been invited to share their most recent
findings.
In addition to the invited speakers, workshop participants are encouraged to
present their own work at a poster session in the afternoon of June 3.
Abstracts of platform and poster presentation, workshop proceedings and a
brief report will be submitted to Reproductive Toxicology for consideration
of publication. Posters will be displayed for June 3-4, 2008.
A separate session on June 5 will be reserved for EPA scientists and
managers to determine remaining research needs and a path to address them.
Acknowledwnents
The workshop was organized by a committee composed of the following
members:
Christopher Lau, NHEERL/ORD (Chair)
John Rogers, NHEERL/ORD
Barbara Abbott, NHEERL/ORD
Douglas Wolf, NHEERL/ORD
Andrew Lindstrom, NERL/ORD
Marc Mills, NRMRL/ORD
Elaine Francis, ORD
Jennifer Seed, OPPT/OPPTS
Cathy Fehrenbacher, OPPT/OPPTS
The organizers wish to thank Ms. Teresa Wall and Mr. Stephen Thompson
of RTD/NHEERL for their enormous efforts to support this workshop.
2
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PFAA Days II Workshop
Auditorium C111A-C, EPA Main Campus,
Research Triangle Park, NC
o�
�z Fq°,% Agenda
Tuesday, June 3, 2008
Introduction
8:30 a.m. — 8:40 a.m.: Introduction — Chris Lau, RTD, NHEERL, ORD
8:40 a.m. — 8:50 a.m.: Welcoming Remarks — Julian Preston, NHEERL, ORD
8:50 a.m. — 9:00 a.m.: Charges of Workshop — Elaine Francis, IO, ORD
Environmental distribution, fate and transport of PFAA — Moderator: Andrew Lindstrom,
HEASD, NERL, ORD
9:00 a.m. — 9:45 a.m.: Historical perspective of PFAA and recent advances in
environmental distribution, fate and transport of these
chemicals — Scott Mabury, Department of Chemistry,
University of Toronto, Canada
9:45 a.m. —10:20 a.m.: PFAA in environmental media — Mark Strynar, HEASD,
NERL, ORD
10:20 a.m.-10:40 a.m.: Sorption of PFOA and PFOS to aquifer sediment
John T. Wilson, GWERD-ADA, NRMRL, ORD
10:40 a.m. —11:00 a.m.: Break
11:00 a.m. —11:40 a.m.: Perfluorinated compounds: From frying pans to polar bears
Kurunthachalam Kannan, Wadsworth Center, NY State
Department of Health
11:40 a.m. —12:15 p.m.: Perfluorinated contaminant research at NIST: Value
assigning Standard Reference Materials (SRMs) and
measuring spatial and temporal trends from the marine
animal specimen bank — Jennifer Keller, Hollings Marine
Laboratory, National Institute of Standards and
Technology, NOAA
12:15 p.m. —1:20 p.m.: Lunch
3
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Bio-monitoring of PFAA — Moderator• Jennifer Seed, OPPT
1:20 p.m. —1:55 p.m.: Update of PFAA 1n the general population
Antonia Calafat, National Center for Environmental
Health, Centers for Disease Control and Prevention
1:55 p.m. — 2:30 p.m.: Bio-monitoring of PFAA in adults and children exposed to
contaminated drinking water — A European perspective
Jiirgen Holzer, Department for Hygiene, Social and
Environmental Medicine, University of Bochum, Germany
2:30 p.m. — 3:05 p.m.: Community exposure to PFOA and health parameters
Edward Emmett, Center of Excellence in Environmental
Toxicology, University of Pennsylvania School of
Medicine
3:05 p.m. — 3:25 p.m.: Break
3:25 p.m. — 4:00 p.m.: C8 Science Panel community study
Tony Fletcher, London School of Hygiene and Tropical
Medicine, UK
4:00 p.m. — 4:35 p.m.: Simulation modeling of PFAA exposure and
phannacokinetics — Harvey Clewell, Center for Human
Health Assessment, The Hamner Institute of Health
Sciences
4:35 p.m. — 5:10 p.m.: Pharmacokinetic modeling of PFAA — Hugh Barton,
NCCT, ORD
5:10 P.M. — 5:15 p.m.: Wrap up — Chris Luu, RTD, NHEERL, ORD
5:15 p.m. — 5:30 p.m.: Break
5:30 p.m. — 7:00 p.m.: Poster session in the B-wing atrium
7:30 p.m.: Reservation for those who want to join a group dinner at
Cafe Parizade in Durham
4
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Wednesday, June 4, 2008
8:15 a.m. — 8:20 a.m.: Re -cap of workshop, house -keeping — Chris Lau, RTD,
NHEERL, ORD
In vitro and in vivo effects of PFAA — Moderator: John Rogers, RTD, NHEERL, ORD
8:20 a.m. — 8:50 a.m.: In vitro screening of PFAA toxicities: the NTP efforts
Ron Melnick, NTP
8:.50 a.m. — 9:20 a.m.: Comparative description of PFAA developmental toxicity:
an update — Chris Lau, RTD, NHEERL, ORD
9:20 a.m. — 9:55 a.m.: Latent effects of PFAA exposure during perinatal
development — Sue Fenton, RTD, NHEERL, ORD
9:55 a.m. —10:15 a.m.: Break
10:15 a.m. —10:55 a.m.: Mechanisms of PFAA toxicity: involvement of PPAR
molecular signals —Barbara Abbott, RTD, NHEERL, ORD
10:55 a.m. —11:30 a.m.: Developmental toxicogenomic studies of PFOA and PFOS
in mice — Mitch Rosen, RTD, NHEERL, ORD
11:30 a.m. —12:05 p.m.: Evidence for involvement of other nuclear receptors in
PFAA toxicity through genomic profiling — Chris Corton,
NHEERL Toxicogenomics Core, ORD
12:05 p.m. —1:10 p.m.: Lunch
1:10 p.m. —1:45 p.m.: Evaluation of PFOA toxicity by the humanized PPARa
transgenic mouse model — Jeff Peters, Department of
Veterinary and Biomedical Sciences, Pennsylvania
State University
1:45 p.m. — 2:20 p.m.: Immunotoxic potentials of PFOA — Jaime DeWitt, ETD,
NHEERL, ORD
2:20 p.m. — 2:55 p.m.: Health effects of perfluorinated compounds — What are the
wildlife telling us? — Margie Peden -Adams, Department of
Pediatrics and Marine Biomedicine and Environmental
Science Center, Medical University of South Carolina
2:55 p.m. — 3:15 p.m.: Break
+7
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Exposure issues of PEAA — Moderator:, Andy Nndstrorn, NERL, ORD
3:15 p.m. — 3:50 p.m.: Method development for the determination of
fluorotelomer alcohols :n soils by gas chromatography
mass spectrometry — Jackson Ellington, ERD, NERL, ORD
3:50 p.m. — 4:25 p.m.: Testing of PFAA release from aged articles of commerce
Zhishi Guo, APPCD, NRMRL, ORD
4:25 p.m. — 5:00 p.m.: Issues and needs for PFAA exposure and health research: A
state perspective — Helen Goeden, Minnesota Health
Department
5:00 P.M. — 5:10 p.m.: Wrap up — Chris Lau, RTD, NHEERL, ORD
5:10 p.m.: Workshop adjourns
0
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U.S. EPA PFAA Days II Workshop - Bios
Barbara Abbott
Dr. Barbara Abbott is a Senior Researcher in the Developmental Biology Branch of the
Reproductive Toxicology 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. She has published over 70 peer -reviewed papers, 15 book chapters and reviews and
received five EPA Scientific and Technological Achievement Awards for outstanding publications.
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 in 2002-2004 for
the Reproductive and Developmental Specialty Section of the SOT. Dr. Abbott is an Associate
Editor for Toxicological Sciences and serves on the Editorial Board of Reproductive Toxicology.
Since 1990, Dr. Abbott has been a research advisor to numerous graduate and post -doctoral
students in cooperation with the University of North Carolina at Chapel Hill and North Carolina
Central University.
Hugh A. Barton
Dr. Barton is a toxicologist with the US EPA developing computational models for use in
biologically based dose -response analyses for chemical risk assessment. He specializes in the
use of physiologically based pharmacokinetic (PBPK) and pharmacodynamic modeling to
address low dose, interspecies, and inter -route extrapolations that critically impact estimating
risks. He has evaluated volatile organic compounds, endocrine disrupting chemicals, and
perfluorinated alkyl compounds, most recently focusing on comparisons across lifestages. Dr.
Barton received a B.S. in Life Sciences from the Massachusetts Institute of Technology,
Cambridge, MA in 1982 and a Ph.D. from the Toxicology Program at MIT in 1988. After working
for consulting companies for 10 years, he joined US EPA in 1999, where he is currently at the
National Center for Computational Toxicology in Research Triangle Park, NC. He is adjunct
Assistant Professor in the Curriculum in Toxicology at the University of North Carolina at Chapel
Hill. He has published more than 40 articles in the scientific literature on xenobiotic metabolism,
PBPK and PD modeling, endocrine disruption, dose response assessment, and risk assessment.
Antonia M. Calafat
Antonia M. Calafat, Ph.D., is a Lead Research Chemist at the Division of Laboratory Sciences,
National Center for Environmental Health (NCEH) of the Centers of Disease Control and
Prevention (CDC) in Atlanta, Georgia, USA, where she serves as Chief of the Personal Care
Products Laboratory. Since starting her tenure at CDC in 1998, 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. Dr. Calafat currently leads several active research
programs for assessing human exposure to emerging chemicals such as phthalates,
environmental phenols (e.g., bisphenol A, triclosan, parabens), and polyfluoroalkyl compounds.
She has developed and maintained extensive collaborative research with leading scientists in
exposure and health assessment. Her research has made relevant contributions to CDC's
biomonitoring program including the CDC's National Report on Human Exposure to
Environmental Chemicals. Dr. Calafat is the recipient of several awards at CDC, including the
Excellence in Supervision Award, the NCEH Leadership in Science Award, NCEH Director's
Award for Superior Mission Response (Science), and the CDC/ATSDR Public Health
Epidemiology and Laboratory Research Award.
DEQ-CFW 00000865

Harvey Clewell
Harvey Clewell is the Director of the Center for Human Health Assessment at the Hamner
Institutes for Health Sciences. He received a Masters in Chemistry from Washington University
and a PhD in Toxicology from the University of Utrecht. His current research interests include the
application of physiologically based pharmacokinetic (PBPK) modeling to the interpretation of
human biomonitoring data, the incorporation of genomic dose -response information in
quantitative risk assessment, and the development of biologically based dose response modeling
approaches.
Christopher Corton
Chris Corton is Leader of the NHEERL Toxicogenomics Core at the National Health and
Environmental Effects Research Laboratory (NHEERL) of the US Environmental Protection
Agency in Research Triangle Park, NC and Senior Research Biologist in the Environmental
Carcinogenesis Division of NHEERL. His research interests include the application of genomic
techniques to understand chemical mode of action, the role of nuclear receptors in chemical
toxicity, the role of oxidative stress and the Nrf2 pathway in modulation of chemical toxicity and
the use of transcript profiling to determine chemical sensitivity at different life stages (young or
old).
Jamie DeWitt
Jamie DeWitt is a Postdoctoral Trainee in the Immunotoxicology Branch of the Experimental
Tnxirningy (liyicinn Within tho Nafinnal I-lcalth nnrr Gnyirr nmen" Gffon+� RCsearct, Laboratory,
under the Office of Research and Development of the U.S., Environmental Protection Agency,
through a cooperative training agreement with the University of North Carolina. She received her
Ph.D. in Environmental Science and Neural Science from Indiana University and completed a
year of postdoctoral training in developmental toxicology at Indiana University before coming to
the EPA. She is an active member in the Society of Toxicology and the Society for
Environmental Toxicology and Chemistry. Her research interests include developmental
immunotoxicolgy and neurotoxicology, environmental and ecotoxicology, and risk assessment.
J. Jackson Ellington
J. Jackson Ellington graduated from University of Georgia with a Ph.D. in medicinal chemistry. He
worked for four years as a research chemist with ARS/USDA. He has worked for the past 24
years as a research chemist at the USEPA, National Exposure Research Laboratory in Athens,
GA where his research included method development for organochlorines, organophosphates
and perchlorate in soil, water, food. His research also included the determination of hydrolysis
kinetics and octanol water partition coefficients important to model development and to the Office
of Solid Waste.
Edward A. Emmett
Edward A. Emmett is Professor and Deputy Director of the Center of Excellence in Environmental
Toxicology at the University Of Pennsylvania School Of Medicine in Philadelphia. He is active in
clinical practice, research and education. Dr Emmett has been listed as one of Philadelphia's Top
Doctors and one of America's Top Doctors. Dr. Emmett graduated in Medicine from the University
of Sydney, completed residency training in Internal Medicine in Australia, and in Occupational
and Environmental Medicine at the University of Cincinnati. After being Assistant and Associate
Professor in Environmental Health, Medicine and Dermatology at the University of Cincinnati, Dr.
Emmett was Professor and Dire of the (�'t� (l Ater for Occupational and Environmental He^aitliat
the Johns Hopkins University from 1978 to 1988. From 1988 to 1996 he was Chief Executive of
the National Occupational Health and Safety Commission in Australia, a body with functions
partially corresponding with those of OSHA, NIOSH, the Bureau of Labor Statistics, and EPA in
the United States. In addition to leading Australia's efforts to implement uniform health and safety
standards, he oversaw the introduction of NICNAS, the Australian equivalent of TOSCA.
DEQ-CFW 00000866

His research contributions have included occupational and environmental skin diseases,
ultraviolet radiation effects on skin and eyes, the toxicity of polyaromatic hydrocarbons, PCBs,
organometals, monomers used in plastics and resins, and more PFAAs. He is author of more
than 150 original papers, book chapters and books in the field of Occupational and Environmental
Medicine. He is certified by the American Board of Toxicology and by the American Board of
Preventive Medicine in Occupational Medicine. Dr. Emmett has been a member of many national
and international committees. He has been Vice Chairman of the Joint ILO/WHO Committee on
Occupational Health; Chairman of the Regional Working Group on Occupational Health for WHO;
a member the WHO Expert Advisory Panel on Occupational Health, Chair of the Implementation
and Methodology Committee for the Institute for Health and Productivity, Chairman of the
Governor's Council on Toxic Substances of the State of Maryland and Chairman of the State of
Maryland Hazardous Toxic Substances Study Commission. He is the "Risk Communicator" for
the UAW -General Motors Occupational Health Advisory Board. Dr. Emmett is a recipient of the
Fight for Sight Citation for Clinical Research, the Kehoe Award of Merit from the American
College of Occupational and Environmental Medicine. His studies of PFOA in Little Hocking
received first place at the 2006 EPA Science Forum, the 2008 Adolph G. Kammer Merit in
Authorship Award from the Journal of Occupational and Environmental Medicine, and the
prestigious 2008 Community -Campus Partnership for Health Award.
Suzanne "Sue" Fenton
Dr. Suzanne "Sue" Fenton received her B.S., M.S., and Ph.D. from the University of WI -Madison.
Her early research focused on artificial insemination and in vitro fertilization in dairy cattle, while
her Ph.D. studies discerned novel signal transduction pathways used for differentiation of the
mammary gland from a proliferative to a secretory tissue during pregnancy and early lactation.
Her postdoctoral studies at the UNC-Chapel Hill Lineberger Cancer Center focused on the roles
and regulation of epidermal growth factor receptor ligands in the mammary gland. Dr. Fenton has
been a Research Biologist at the US EPA's Reproductive Toxicology Division since October of
1998. Her current research involves identification of the effects of environmental components on
early development, pubertal timing and Iactational function of the mammary gland. Her research
efforts have three times been awarded a Level III EPA Scientific and Technical Achievement
Award, a SOT Reproductive and Developmental Toxicology Specialty Section "Best Paper" in
Toxicological Sciences award, and her work on the long-term effects of developmental exposure
to a perfluorinated alkyl acid was highlighted in the May 2007 issue of Environmental Health
Perspectives.
Tony Fletcher
Dr. Tony Fletcher, member of the Court -appointed C8 Science Panel, is a senior researcher and
lecturer at the Public and Environmental Health Research Unit in the London School of Hygiene &
Tropical Medicine (LSHTM) which he joined in 1992. Tony Fletcher has been active in
environmental and occupational epidemiology and risk assessment, for over 25 years. He is
Adjunct Research Professor in Environmental Health in the School of Public Health, Boston
University, Massachusetts, USA. He has spent two periods working at the International Agency
for Research in Cancer in Lyon, France. He has directed and recently completed multi -country
European studies arsenic contamination and cancer, and particulate air pollution and children's
respiratory disease. Other research includes occupational epidemiology studies in foundries and
synthetic fiber manufacture, and risks related to pesticides and welding. He was President of the
ISEE International Society for Environmental Epidemiology for two years 2004-5, and co-
organizer of a number of conferences on health and the environment, including the "Big Smoke"
commemorating the 50th anniversary of the 1952 London Smog.
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Elaine Francis
Dr. 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 28 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.
Helen Goeden
Dr. Goeden received her B.S. in Biology and Chemistry and her Ph.D. in Environmental Health
and Toxicology. After spending a year and a half in a postdoctoral position at the University of
Calgary researching developmental effects or low-level hydrogen sulfide exposure, Dr. Goeden
moved to California. While in California, Dr. Goeden worked at a small environmental consulting
firm and at the University of California at Berkeley. Her work involved development of toxicity
values for California Office of Environmental Health Hazard Assessment and conducting risk
assessments for waste combustion facilities. In 1992 Dr. Goeden took a position as a Research
Scientist at the Minnesota Pollution Control Agency. While at the Pollution Control Agency her
major responsibilities involved development and refinement of risk assessment methodologies
(including methodology for the derivation of multi -duration soil criteria), chemical specific toxicity
assessments, and site -specific risk assessments. In 2001 Dr. Goeden joined the Health Risk
Assessment Unit of the Environmental Health Division of the Minnesota Department of Health
(MDH). Currently, her main responsibilities are related to the evaluation of groundwater
contaminants. Her role is to evaluate recent scientific research to identify the best science
available and to determine its application in making public health policy decisions that are
protective of susceptible (e.g., heightened sensitivity or highly exposed) populations potentially
exposed to groundwater and drinking water contamination.
Zhishi Guo
Zhishi Guo is an Environmental Scientist in the Indoor Environment Management Branch, Air
Pollution Prevention and Control Division, National Risk Management Research Laboratory,
Office of Research and Development, U.S. EPA. He received his Ph.D. degree in Environmental
Science and Engineering from University of North Carolina at Chapel Hill. Dr. Guo is specialized
in characterization of indoor pollution sources and indoor environmental quality and exposure
modeling.
Jurgen Holzer
Jurgen Holzer is a Medical Scientist in the Department of Hygiene, Social and Environmental
Medicine, Ruhr -University Bochum, Germany. He is an active member of the Society of Hygiene,
Environmental and Public Health Sciences (GHUP, Germany) and the German Society for
Medical Informatics, Biometry and Epidemiology (GMDS). His research interests include bio-
monitoring of ETS, PAH, PCDD/F, PFAA in epidemiological studies, evaluation of DNA damage
and repair and risk assessment.
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Kurunthachalam Kannan
Dr. Kurunthachalam Kannan is a Research Scientist at Wadsworth Center, New York State
Department of Health in Albany, New York. He is the Chief of the Organic Analytical Laboratory
at the Center and also holds a joint appointment as a Professor at the Department of
Environmental Health Sciences, School of Public Health, SUNY at Albany. Dr. Kannan's
research interests are in understanding sources, pathways and distribution of persistent organic
pollutants in the environment. Dr. Kannan has published more than 225 research articles in peer -
reviewed journals, 11 book chapters and edited a book and is one of the top 10 most highly cited
researchers (ISI) in Ecology/Environment in the world. Dr. Kannan is a receipt of several awards
and honors through his career and SETAC's Weston F Roy Environmental Chemistry award in
1999. He received his PhD from Ehime University, Japan and a Bachelor's degree from Tamil
Nadu Agricultural University in India. He is an editor of Environmental Chemistry section of
Chemosphere.
Jennifer Keller
After becoming SCUBA certified at age 14, Jennifer Keller, embarked upon an unwavering pursuit
into a career in marine biology. She received her Bachelor's of Science in Biology with a minor in
Environmental Science at Indiana University. During her undergraduate studies, she performed
three independent research projects, one of which at the Woods Hole Oceanographic Institution.
All three projects focused on toxicology, which steered her towards a Ph.D. at Duke University in
Marine Environmental Toxicology. Her dissertation stemmed from a collaboration among the
Duke Marine Laboratory, National Marine Fisheries Service, and National Institute of Standards
and Technology (NIST) to measure the concentrations of persistent organic pollutants (POPs)
accumulated by sea turtles and further investigate their health effects in these endangered
marine creatures. Dr. Keller received a National Research Council post -doctoral fellowship to
work at NIST in 2003 and has continued to work for NIST as a Biologist since. She is responsible
for developing analytical methods to measure environmental contaminants that are of an
emerging concern, like brominated flame retardants and perfluoro alkyl stain -resistant
compounds. She is also an Adjunct Professor at the College of Charleston's Grice Marine
Laboratory and the Vice President of a non-profit marine science education and research
organization, Marine Science and Nautical Training Academy (MANTA). In her free -time, she
enjoys traveling, boating with her family, yellow lab and friends, photography, and boogie
boarding.
Christopher Lau
Christopher Lau is a Lead Research Biologist in the Developmental Biology Branch of the
Reproductive 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 Pharmacology from Duke University, and postdoctoral
training in Neuroanatomy from the Medical College of Pennsylvania. He is an active member of
the Society for Neuroscience, Society of Toxicology, Teratology Society, International Society for
Developmental Origins of Heath and Diseases, and Fetal and Neonatal Physiology Society. His
research interests include developmental toxicology, teratology, and risk assessment modeling.
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 biomarker 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
DEQ-CFW 00000869

(LC/MS) analysis to measure trace level contaminants in biological matrices and environmental
media.
Scott A. Mabury
Mabury received his undergraduate chemistry degree from Northland College (1984) after which
he spent a few years as a Peace Corps Volunteer on the island of Mindoro in the Philippines.
Environmental photochemistry focused on aqueous hydroxyl radical took him to the University of
California -Davis where he completed a PhD (1993) in Environmental Chemistry under the
mentorship of Prof. Donald Crosby. Following a short PDF he took up an assistant professorship
in chemistry at the University of Toronto to build an environmental chemistry undergraduate and
graduate program. UofT Chemistry now has 7 full-time environmental chemistry faculty with a
vibrant and impressive complement of PhD and MSc students. Undergraduate courses are well
populated and received at all levels with Mabury focusing on a third year environmental chemistry
(150 enrolled annually) and a fourth year advanced analytical environmental course with an
advanced laboratory. While maintaining interest in aquatic photochemistry, the main thrust of the
Mabury group has focused on the role the fluorine atom plays in the fate, disposition, and
persistence of fluorinated pesticides, pharmaceuticals, consumer and industrial products.
Significant effort has focused on the PFCA class of chemical pollutants with some success
elucidating the sources of these contaminates and the processes at play in their global
dissemination. His group has discovered a number of new contaminants, has determined the
mechanism and kinetics for multiple environmental processes, and has worked to influence
industry and regulators towards developing tnendlier chemical architectures. The Mabury group
has —125 publications, with roughly 85 in the area of fluorinated chemicals, and has delivered —90
invited talks. The group currently has 5 MSc and 4 PhD students, having graduated 10 MSc and
9 PhD students; four former Mabury group students are currently faculty members. Mabury has
been honored with four teaching awards, a Premier's Research Excellence Award and an Alumni
Award from his alma mater. Currently, Mabury is winding up a stint as Chair of Chemistry having
lead the hiring of 10 new faculty, massive expansion of the graduate program, and the renovation
of over $15M of teaching and research laboratories.
Ron Melnick
Dr. Ron Melnick is senior toxicologist and director of special programs in the Environmental
Toxicology Program at the National Institute of Environmental Health. He has worked at the
National Institute of Environmental Health since 1980, where he has been involved in the design,
monitoring and interpretation of toxicity and carcinogenesis studies, as well as research on the
health effects of environmental and occupational agents. He spent a year as an agency
representative to the White House Office of Science and Technology Policy to work on
interagency assessments of health risks of environmental agents and on risk assessment
research needs in the federal government. Dr. Melnick's research has advanced the
understanding of the toxicity of such widely used industrial chemicals as butadiene, isoprene,
glycol esters and drinking water disinfection by-products such as chloroform, and the cancer -
causing potentials of DEHP and MTBE. The author or co-author of more than 140 journal articles,
book chapters and technical reports related to the potential health effects of environmental agents,
Dr. Melnick has organized several national and international symposiums and workshops on
health risks associated with exposure to toxins. He has served on numerous scientific review
boards and advisory panels, including those of the North Carolina Department of Environment
and Natural Resources and the U.S. Environmental Protection Agency.
DEQ-CFW 00000870

Margie Peden -Adams
Margie Peden -Adams completed her Ph.D in Environmental Toxicology from Clemson University
in 1999. Following graduation, she finished a post -doctoral fellowship in Rheumatology and
Immunology at the Medical University of South Carolina, which was followed by a faculty position
in the Department of Clinical Laboratory Services. She is currently faculty in the Department of
Pediatrics and the Marine Biomedicine and Environmental Science Center at MUSC and holds
adjunct faculty appointments at the College of Charleston and Mystic Aquarium. Her research
focuses on the sublethal toxic effects of environmental contaminants and utilizes various
laboratory, wildlife, and in vitro models to assess effects on immune, reproductive, developmental,
and endocrine endpoints.
Jeffrey Peters
Jeffrey Peters is associate professor of molecular toxicology at the Pennsylvania State University.
His research interests include the roles of the peroxisome proliferator -activated receptors
(PPARs) in the regulation of homeostasis, toxicology, and carcinogenesis with extensive
application of null and transgenic mouse models. The goal of his research is to identify functional
roles of the PPARs in the etiology and prevention of carcinogenesis. Dr. Peters is also conducting
research to delineate the role of the PPARs in the regulation of homeostasis, including body
composition, tissue specific gene expression, serum lipid biochemistry, and atherosclerosis.
Results from this research will determine mechanisms that PPARs regulate physiological lipid
metabolism using different activators reported to interact through PPARs. He earned a Ph.D. in
nutrition science from the University of California at Davis and did his postdoctoral training at the
University of California at Davis and the National Cancer Institute.
R. Julian Preston
R. Julian Preston, Ph.D. is currently serving as Acting Associate Director for Health for the
National Health and Environmental Effects Research Laboratory of the U.S. EPA. He served as
Director of the Environmental Carcinogenesis Division at the EPA from 1999 until August 2005.
Prior to this appointment, he served as the Senior Science Advisor at the Chemical Industry
Institute of Toxicology in Research Triangle Park, North Carolina from 1991-1999. He was
employed at the Biology Division of the Oak Ridge National Laboratory in Oak Ridge, Tennessee
from 1970-1991 where he was appointed Section Head, Human Genetics in 1987. He also
served as Associate Director for the Oak Ridge — University of Tennessee Graduate School for
Biomedical Sciences. He is currently Adjunct Professor at Duke University and North Carolina
State University. Dr. Preston received his BA and MA from Peterhouse, Cambridge University,
England in genetics and his Ph.D. from Reading University, England in radiation genetics. Dr
Preston is an Editorial Board Member of Mutation Research, Environmental and Molecular
Mutagenesis, Environmental Health Perspectives, Chemico-Biological Interactions and Health
Physics. Dr. Preston's research and current activities have focused on the mechanisms of
radiation and chemical carcinogenesis and the approaches for incorporating these types of data
into cancer risk assessments. In particular, he is developing approaches for addressing how key
events for tumorigensis can be used to select informative bioindicators of response.
John M. Roaers
Dr. John M. Rogers is Chief of the Developmental Biology Branch in the Reproductive Toxicology
Division at NHEERL/ORD. He earned a Ph.D. in Biology from the University of Miami, and
received a National Research Service Award from the National Eye Institute for postdoctoral work
at the University of California at Davis. He joined the EPA after his postdoctoral fellowship. His
research interests include developmental biology, mechanisms of abnormal development,
developmental nutrition, and risk assessment. Dr. Rogers has authored over 90 journal articles
and chapters, and has been an invited speaker or participant at EPA, NIEHS, FDA and EPRI
workshops. He serves on research grant review panels for numerous organizations. He is a
member of the Society of Toxicology, the Teratology Society and the Society for Experimental
Biology and Medicine. He has taught courses in cell and developmental zoology at North Carolina
DEQ-CFW 00000871

State University and is an Adjunct Associate Professor in the Curriculum in Toxicology at the
University of North Carolina, Chapel Hill.
Mitchell B. loosen
Mitchell Rosen is a Research Biologist at the U.S. Environmental Protection Agency in the
Research Triangle Park, North Carolina. His position is affiliated with the Gamete and Early
Embryo Biology Branch of the Reproductive Toxicology 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 technology to understand the potential mechanisms associated with
reproductive toxicants.
Jennifer Seed
Dr. Jennifer Seed is a Branch Chief with the Office of Pollution Prevention and Toxics, Risk
Assessment Division, Existing Chemicals Assessment Branch of the U.S. EPA. Jennifer has been
the lead for the Agency's hazard and risk assessment activities of PFOA and other perfluorinated
compounds for the last 9 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 actively involved in a
number of activities, both within the EPA as well as with other organizations that have focused on
risk assessment issues. She is the chair of the human health effects subqroup of the Agency_ 's
Risk Assessment Forum and has been involved in Agency efforts to harmonize cancer and
noncancer approaches for risk assessment. She has been involved in Agency and OECD efforts
to develop and harmonize test guidelines and risk assessment guidelines for developmental and
reproductive toxicity. Jennifer received a PhD in developmental biology from the University of
Washington.
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 fate and transport of
perfluorinated compounds environmental media.
John Wilson
John Wilson is a research microbiologist in GWERD's Subsurface Remediation Branch. He has
a B.S. in Biology from Baylor University, an M.A. in Microbiology from the University of California
at Berkeley, and a Ph.D. in Microbiology from Cornell University. He has worked at the R.S. Kerr
Environmental Research Center in Ada, Oklahoma since 1978. Dr. Wilson conducts research on
in -situ bioremediation of fuel spills in the subsurface, and on natural attenuation of BTEX
compounds and chlorinated solvents in ground water. In addition to his research activities, Dr.
Wilson provides training and technical assistance to the EPA regions and to state agencies on
natural attenuation of chlorinated solvents and BTEX compounds in ground water.
DEQ-CFW 00000872

U.S. EPA PFAA Days II Workshop - Abstracts
Author: Scott A. Mabury
Title: Historical Perspectives of PFAAs and Recent Advances in Environmental Distribution, Fate
and Transport
Affiliation: Department of Chemistry, University of Toronto
Abstract:
Perfluorinated acids (PFCAs and PFOS) are widely disseminated in the global environment and
appear at high concentrations in humans and in Arctic mammals; a new PFA, the
perfluorophosphonic acid or PFPAs, was recently discovered in our lab. We have developed the
'precursor alcohol atmospheric reaction and transport' or PAART theory to potentially explain
these observations. Residual fluoro-alcohols are significant in fluorinated polymers and
surfactants (food contact paper coatings) and may contribute significantly to the global burden,
though we know little about the stability of the linkage chemistry within the fluorinated materials.
Recent experiments have shown the ester and phosphate esters in monomers and surfactants
are readily hydrolyzed through microbial and mammalian metabolism. The fluoroalcohols (e.g.
FTOHs) are readily oxidized, via reactive intermediates, to the resulting PFCAs. Some of these
intermediates have been shown to be highly toxic to D. Magna (ie 10:2 FTCA) or readily react
with GSH (the acrylic aldehydes). These fluoroalcohols are also readily found in the atmosphere
and have been shown to undergo atmospheric transport and OH driven transformation reactions
to yield the observed perfluorinated acids. Model studies suggest significant production of these
acids in remote Arctic regions have been confirmed by flux measurements into the ice cap.
Temporal studies of biota contamination yield body burdens that appear to closely match
production changes by industry. 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.
Author: Mark StrYnar', Andy Lindstrom', Shoji Nakayama 2, Amy Delinsky', Jessica Reinert and
Laurence Helfant
Title: PFAAs in Environmental Media
Affiliation: 'U.S. Environmental Protection Agency, Research Triangle Park, NC. 2Oak Ridge
Institute for Science and Education, Oak Ridge, TN. 3National Caucus & Center on Black Aged
Inc., Washington D.C.
Abstract:
Perfluorinated Alkyl Acids (PFAAs) are a globally distributed class of compounds that are found in
humans, wildlife, and environmental samples. Determination of 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. 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
+ract rl f.-.-.m di lks �rfacee �V f4r fish nil house dust) using an organic
exu a�. eu from i i environmental iiicuia �oui iva.c v'u ivi , � o� �, Sv � .. y ... 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 GC -
MS. 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 media will be discussed and results from recent studies will be presented.
DEQ-CFW 00000873

Author: Ferrey, M.L.', Adair, C2, and Wilson, J.T.`
Title: Sorption of PFOA and PFOS to Aquifer Sediment
Affiliation: 'Minnesota Pollution Control Agency, St. Paul, Minnesota, 2U.S. EPA, R.S. Kerr
Research Laboratory, Ada, Oklahoma
Abstract:
During its years of operation, the Washington County Sanitary Landfill near St. Paul, Minnesota
accepted both municipal and industrial solid waste. Several years.of ground water monitoring
performed by the MPCA indicates that, some of the waste disposed of at this landfill contained
PFOA. The PFOA has leached into the ground water and moved with the ground -water flow. It
has also moved deeper, affecting the bedrock aquifer where it was found at low levels.
As part of a risk evaluation, a microcosm study was performed to predict transport and fate of
perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) in leachate from the landfill.
Realistic concentrations of PFOA and PFOS were added to microcosms constructed with
sediment that was collected from beneath the water table at the Washington County Landfill.
Microcosms were then sealed and incubated in the laboratory. Three microcosms of each
treatment were sacrificed at quarterly intervals for analysis.
Aqueous concentrations of PFOA and PFOS increased in the microcosms over the incubation
period. Shortly after the addition of PFOS and PFOA, the adsorption constant, Kd, averaged
0.9'%48 L Kg-1 for PFOA and 1.1503 L Kg-1 for PFOS. At 574 days, the Kd averaged 0.0690 L
K--1 and 0 1973 I K-- 1 for PFOA and PFOS, respe tivcly I ;r,__, ,.s ail,. -1-t .
.y �+.- y . i�.oNcuuvciy. "111-I I\J IJ,IVJJIVII UI LIIO UCILQ
generated slopes of -0.002 L Kg-1 day-1 for PFOA and-0.0014 L Kg-1 day-1 for PFOS.
Corresponding retardation constants were 2.3 and 10.2 for PFOA and PFOS at the beginning of
the study, which decreased to 1.55 and 2.58, respectively, after 574 days.
The fraction organic carbon in the sediments was 0.034%. The Koc after 574 days of incubation
was 203 L Kg-1 and 580 L Kg-1 for PFOA and PFOS, respectively. Higgins and Luthy (ES&T 40:
7251-7256, 2006) determined values of Koc for PFOA and PFOS for freshwater sediments of 130
L Kg-1 and 480 L Kg-1 for PFOA and PFOS, respectively. After 574 days of incubation, there
was good agreement between Koc for sediment and Koc for aquifer material. At the
concentrations of organic material found in water supply aquifers, both PFOA and PFOS should
be highly mobile.
The change in the extent of sorption was not expected. The decrease in the adsorptive properties
of PFOA and PFOS observed in this study may be due to changing redox conditions over time in
the microcosms. It can be rationalized as follows: The sediment as collected was impacted with
leachate, but had a red color, indicating the presence of iron(III) minerals. The PFOA and PFOS
may have initially sorbed to the iron(III) minerals, and then were released back into pore water as
the iron(III) minerals were consumed or modified by iron reducing bacteria.
No evidence of degradation of PFOA or PFOS was observed.
Author: Kurunthachalam Kannan
Title: Perfluorinated Compounds: From Frying Pans to Polar Bears
Affiliation: Wadsworth Center, New York State Department of Health, & School of Public Health,
SUNY at Albany, USA
Abstract:
Perfluoroalkyl surfactants (PASs) are class of fluorochemicals manufactured for their unique
chemical stability and surface -tension lowering properties. Following several decades of
commercial use, f ASa have been discovered to be globally distributed, persistent erivirurimerilaI
contaminants. Evidence of in vivo toxicity, and the occurrence of PASs in the blood of general
populations, has created public health concern.
DEQ-CFW 00000874

Our current research interests are in the areas of identifying sources, pathways and distribution of
PASs in the environment. PASs and related fluorinated compounds are used in a variety of
consurner products including non-stick cookware and microwave popcorn bags. We identified and
measured PASs released from non-stick coated cookware into the gas phase under normal
cooking temperatures. Our results indicate that PFOA and telomer alcohols are not completely
removed during the fabrication process of the non-stick coating for cookware. Rather, they remain
residual in the surface and may be off -gassed when heated to normal cooking temperatures, and
contribute to a source of human and environmental exposures.
PASs are ionic and highly mobile in the aqueous environment. PASs present in several consumer
products can ultimately be released into wastewaters from domestic, commercial and industrial
sources and be directed to wastewater treatment plants (WWTPs). We measured concentrations
and fate of several PASs in six WWTPs in New York State. Primary treatment was found to have
no effect on the mass flows of PASs. Secondary treatment by activated sludge significantly
increased the mass flows of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and a
few long -chain PFCAs.
PASs have been found at higher concentrations in predators, than in their diet. We measured the
occurrence of PASs in natural waters, lower trophic organisms, sport fish, birds, and aquatic
mammals. PFOS and PFOA are ubiquitous in New York waters. Overall, average concentrations
of PFOS in fish were 8850 —fold greater than those in surface water. An average
biomagnification factor of 8.9 was estimated for PFOS in birds relative to that in fish. Significance
of dietary fish in food chain accumulation of PFOS is documented.
Our current studies focus on human and wildlife biomonitoring on a global scale as well as
oceanic survey of PASs to understand their pathways and distribution in the environment.
Perfluorinated contaminant research at NIST: Value assigning Standard Reference Materials
(SRMs) and measuring spatial and temporal trends from the Marine Environmental Specimen
Bank.
Author: Jennifer M. Keller
Title: Perfluorinated Contaminant Research at NIST: Value Assigning Standard Reference
Materials (SRMs) and Measuring Spatial and Temporal Trends from the Marine Environmental
Specimen Bank
Affiliation: Hollings Marine Laboratory, Analytical Chemistry Division, National Institute of
Standards and Technology (NIST)
Abstract:
Some of the members of the Analytical Chemistry Division of NIST are located in the Hollings
Marine Laboratory (HML). Within HML, NIST maintains an organic and inorganic chemistry
laboratory, a nuclear magnetic resonance core facility, and the Marine Environmental Specimen
Bank (www.hml.nist.gov). The research presented today will focus on the quantification of
perfluorinated contaminants (PFCs) in Standard Reference Materials (SRMs) and in specimen
bank samples.. Standard Reference Materials (SRMs) are homogeneous, well -characterized
materials that may be used to validate measurement methods (www.nist.govisrm). NIST, in
collaboration with the Centers for Disease Control and Prevention and the 3M Corporation, are
measuring background concentrations of 12 PFCs in a variety of environmental and biological
reference materials, including human serum (SRMs 1957, 1958), human milk (SRMs 1953, 1954),
fish tissue (SRMs 1946, 1947), mussel tissue (SRMs 1974b, 2977), sediments and sludge (SRMs
1941 b, 1944, 2781), house dust (SRM 2585), and marine mammal liver. Preliminary data
will be presented for selected SRMs. In addition, we utilized samples from the Marine
Environmental Specimen Bank to monitor temporal trends and sex differences of three PFCs in a
marine mammal species. Liver samples from 49 adult white -sided dolphins (Lagenorhynchus
acutus) that stranded in Massachusetts from 1993-2005 were analyzed by the 3M Corporation.
Perfluorooctane sulfonate (PFOS) was the most abundant PFC, and males had higher PFOS
DEQ-CFW 00000875

concentrations than females. Considering only males, PFOS concentrations were stable over the
entire time period, but declined from 1999-2005. Perfluorooctanoic acid (PFOA) was below the
detection limit (=3 ng/g) in most samples. Perfluorononanoic acid (PFNA) showed an increasing
temporal trend in males with a doubling time of =8 y. The possible reasons for these sex
differences and temporal trends will be discussed. Through the tools available at NIST, we
anticipate that use of our SRMs will improve analytical PFC measurements and that support for
the Specimen Bank will continue to allow retrospective studies that can capture the emergence
and trends of environmental contaminants.
Author: Antonia M. Calafat, Lee -Yang Wong, Kayoko Kato, Larry L. Needham
Title: Update of PFAA in the General Population
Affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers
for Disease Control and Prevention, Atlanta, GA 30341
Abstract:
Polyfluoroalkyl compounds (PFCs) can be used in multiple commercial applications, including
surfactants, lubricants, paints, polishes, food packaging, and fire -retardant foams. The Centers
for Disease Control and Prevention's National Health and Nutrition Examination Survey
(NHANES), which includes exposure assessment to selected environmental chemicals of the US
population at various life stages, has confirmed that exposure to PFCs is widespread among the
general population 6 vears of age an nlrier Alsn of interest, cmmnared to data from NHANES
1999-2000, data from NHANES 2003-2004 are consistent with reduced population exposure to
several PFCs, most likely because of recent efforts of industry and government. However, despite
the important advances in our knowledge of human exposure to PFCs in the United States, little
is known about the extent of this exposure of pre -adolescent children, because the amount of
serum collected from young children in NHANES is limited. To fill these data gaps, we have
analyzed pooled serum samples from 3-1 1-year-old children who were participants of NHANES
2001-2002. The concentrations of 9 PFCs were estimated by use of on-line solid -phase
extraction coupled to isotope dilution -high performance liquid chromatography -tandem mass
spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoate, perfluorohexane sulfonate
(PFHxS), perfluorononanoic acid, 2-(N-ethyl-perfluorooctane sulfonamido) acetate, and 2-(N-
methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH) were detected in all pools. The
unweighted mean concentrations were higher for PFOS than for the other PFCs. The
concentrations of some PFCs differed by race/ethnicity. The measurements of PFCs in these
samples will complement the measurements previously conducted on the 2001-2002 NHANES
participants aged 12 years and older.
Author: Jurgen Holzer
Title: Bio-Monitoring of PFAA in Adults and Children Exposed to Contaminated Drinking Water —
An European Perspective
Abstract:
Background: In 2006, contamination of drinking water with Perfluoroalkyl Acids (PFAAs) was
reported from Arnsberg, Germany (Z PFAAs: 598 ng/L, PFOA: 0.519 pg/L; Skutlarek et al. 2006).
40,000 residents were affected. Immediately after the increased PFOA-levels were observed,
German Drinking Water Commission of the German Ministry of Health at the Federal
Environment Agency established guide values for human health protection for composite PFOA
and PFOS-concentrations: health based precautionary value (long term minimum quality goal) for
non-genotoxic substances: 0.1 pg/L, strictly health based guide value for safe lifelong exposure of
all population groups: 0.3 pg/L; precautionary action value for intants: 0.5 pg/L; precautionary
action value for adults: 5,0 ug/L (DWC 2006)_ Based on the results of an extensive environmental
monitoring program, Federal health authorities concluded, that PFAA-contamination of
DEQ-CFW 00000876

agricultural land occurred by the wide-ranging use of soil conditioner, which has been mingled
with industrial waste (Wilhelm et al. in press).
Objective: A biomonitoring study was performed to assess the internal exposure of Arnsberg's
residents to PFAAs in comparison to reference areas.
Study population: 170 children (5-6 years old), 317 mothers (23-49 years) and 204 men (18-69
years) were included in the cross -sectional study.
Methods: Individual consumption of drinking water and personal characteristics 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.
Results:
PFOA-levels in blood plasma of residents living in Arnsberg were 4.4-8.3 times higher compared
to the reference population (ratios based on geometric means: children 22.1/4.8 pg/L, mothers
23.4/2.8 pg/L, men 25.3/5.8 pg/L). Consumption of tap water at home was associated with PFOA-
blood-concentrations in Arnsberg (P < 0.01). PFHxS-concentrations were significantly increased
in Arnsberg compared with controls (P < 0.05). PFBS was detected in 33 % (4 %, 13 %) of the
children (women, men) in Arnsberg compared to 5 % (0.7 %, 3 %) in the reference areas
(P < 0.05). Further details are reported in H61zer et al. (2008).
Conclusions: PFOA-concentrations in blood plasma of children and adults exposed to PFOA-
contaminated drinking water were 4-8fold increased compared with controls.
References:
DWC. 2006. (Drinking Water Commission of the German Ministry of Health at the Federal
Environment Agency). 2006. Provisional evaluation of PFT in drinking water with the guide
substances perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) as
examples. Available: http://www.umweltbundesamt.de/uba-info-presse-a/hintergrund/pft-in-
drinking-water.pdf) [accessed 29.4.2008].
Holzer J, Midasch O, Rauchfuss K, Kraft M, Reupert R, Angerer J, Kleeschulte P, Marschall N,
Wilhelm M. Biomonitoring of Perfluorinated Compounds in Children and Adults Exposed to
Perfluorooctanoate-Contaminated Drinking Water. Environ Health Perspect 116(5): 651-
657.
Skutlarek D, Exner M, Farber H. 2006. Perfluorinated surfactants in surface and drinking waters.
Environmental science and pollution research international 13(5): 299-307.
Wilhelm M, Kraft M, Rauchfuss K, H61zer J. in press. Assessment and management of the first
German case of a contamination with perfluorinated compounds (PFC) in the region
Sauerland, North Rhine-Westphalia. J Toxicol Environ Health A.
Author: Edward A. Emmett, MD, MS
Title: Community Exposure to PFOA and Health Parameters
Affiliation: University of Pennsylvania, School of Medicine
Abstract:
We have studied Perfluorooctanoate (PFOA) in the vicinity of Little Hocking, a contaminated
community in Southeastern Ohio. PFOA is persistent in humans and the environment and is
ubiquitous at low levels in human serum. The reported half-life of PFOA in human serum is about
4 years. At the time our study was initiated the sources(s) of general population exposure were
unknown and no studies of PFOA effects on the health of the general population had been
reported. The toxicokinetics of PFOA in experimental animals and humans are so different that
extrapolations from animals, without human data, can have little or no validity. PFOA is a potent
hepatotoxin and carcinogen in rodents but the mechanism of action may not be relevant to
humans. PFOA has been reported to cause developmental delays in rats.
DEQ-CFW 00000877

Residents of the Little Hocking Water Association (LHWA) reticulation area have potential water
and air PFOA exposure from nearby Fluoropolymer production. We formed an environmental
justice partnership with the community to: (1) determine the levels of PFOA in the blood of
residents in the Little Hocking water service area and compare these with levels in other
populations, (2) determine the major sources of exposure (water, air, other) influencing the blood
C8 levels, and (3) determine whether there is an association between blood C8 levels and levels
of markers of health effects.
We measured serum PFOA and administered questionnaires to a stratified random sample of
324 subjects from 161 households, plus 54 individuals from 35 volunteer households selected by
lottery. These residents were selected from two areas, one with higher potential air exposure, the
other with negligible air exposure, both sharing the same water supply. PFOA was measured by
high performance liquid chromatography (HPLC)/tandem MS, confirmed using C13 labeled
standards. The levels of PFOA in residents of the Little Hocking water district greatly exceeded
US general population medians of—5ng/mL. Control individuals from Philadelphia had values in
the normal population range.
Occupational exposure from production processes using PFOA and residence in the water district
made additive contributions to serum PFOA; no other occupations made discernable
contributions. Median serum PFOA for residents with both air and water exposure was 326ng/mL
and 367ng/mL for water exposure alone, indicating no contribution from air exposure. Median
PFOA was 55ng/mL for current consumers of bottled/spring/cistern water. In well water users,
serum PFOA reflected well water PFOA. The median serum/water PFOA ratio for LHWA water
users was iva. Se urn PFOA was sigruncahuy nigher in children aged <6 years and those aged
>60. No gender differences were observed. For residents whose sole water source was Little
Hocking water, we used the General Estimating Equation to assess the contribution of other
variables: the model of best -fit included age, tap water drinks per day, servings per week of
homegrown fruit and vegetables, and carbon filter use. Eating locally harvested meat and game
was not significant. The association with eating homegrown fruits and vegetables may reflect
water use in cooking, cleaning, and canning. Serum PFOS values did not show the same
association with water source.
We also explored the relationship between serum PFOA and disease biomarkers. Serum PFOA
was not significantly associated with biomarkers of potential liver, renal, hematologic, or thyroid
disease or with serum cholesterol. There was no significant association between serum PFOA
and a history of diagnosis or treatment for liver or thyroid disease. We did not initially study
potential cancer or developmental effects, some studies are continuing. We are also studying the
distribution of PFOA to breast milk in mothers in the area.
The results of our findings were made available to the community. As a result of the findings of
high serum PFOA, bottled water was made available to residents in the community, Over 77% of
LHWA customers accepted the offer. We performed a follow-up study of 64% of the participants
in the original study, approximately 15 months after the release of our original findings. Of those
previously drinking unfiltered LHWA water 86% had changed to bottled water, and over 95% had
made some change in their residential drinking water. The median reduction in serum PFOA
levels was 26%. We observed age -related differences in the changes in blood PFOA. The
LHWA has now installed an advance filtration system which appears to be eliminating PFOA from
the reticulated water.
Our findings have raised a number of additional research questions such as: the relationship of
PFOA to fruit and vegetable consumption, age and gender effects on effective PFOA half-lives,
and the relative effectiveness of different drinking water interventions.
These studies to date indicate the usefulness of a community -investigator partnership, with
independent funding from government agencies, in answering important questions relevant to
hiunidns about envitoirmental exposure and effects In unique exposure circumstances.
DEQ-CFW 00000878

Author: Tony Fletcher
Title: C8 Science Panel Community Study
Affiliation: London School of Hygiene and Tropical Medicine, UK
Abstract:
In February 2005, West Virginia Circuit Court approved a class action settlement in a lawsuit
concerning releases of PFOA (or "C8"), from DuPont's Washington Works in West Virginia. The
settlement, among other provisions, established a "Science Panel" of three epidemiologists: Dr.
Tony Fletcher (London School of Hygiene and Tropical Medicine), Dr. David Savitz (Mt. Sinai
School of Medicine, New York) and Dr. Kyle Steenland (Emory University, Atlanta). Our role is to
conduct a Community Study, and subsequently evaluate whether there is a "probable link"
between C8 exposure and any human disease. (www.c8ciencepanel.org)
After an initial review of the evidence we established the C8 Community Study as a set of
interlinked studies, addressing a number of health outcomes and encompassing several
epidemiological designs and data sources. Some draw on a baseline set of blood analyses and
questionnaire data from 69030 community participants - the C8 Health Project - set up under the
settlement in parallel with the Science Panel.
Cross sectional analyses of the C8 Health Project data, principally analyses of associations
between clinical chemistry and C8 measured at the same time in serum samples;
Health event data (including births, and self reported disease) in the C8 Health Project population
in relation to the reconstructed historical exposure profile;
Longitudinal studies of the C8 Health Project population in subgroups of those with additional
consent to Science Panel studies — multiple repeated sampling of C8 for studying the half life of
C8; repeat sampling of C8 and clinical parameters to assess response to changes in C8 levels;
examination of neurobehavioral development in relation to C8 in a sample of children; follow up of
40000 in the exposed community to assess morbidity and mortality in relation to the history of C8
exposure.
Longitudinal study of workers in the plant.
Ecologic studies of routine data: studies of reproductive and cancer outcomes, with exposure
classification to C8 in water supplies by area of residence at birth/cancer registration.
The first phase of work is under way, including data checking, QA and analyses of the cross
sectional data; reconstruction of C8 exposures and repeat sampling of individuals in the half life
study. Associations of interest are being assessed for a number of outcomes in the cross
sectional study including lipids, uric acid, immune biomarkers, liver and thyroid function and self
reported disease. The population of 69030 participants had a range of concentrations up to
22000 pg/I of PFOA in serum, with a median of 28.2 pg/I (interquartile range 13.4-70.6 pg/1 ). For
PFOS the median was 20.2 pg/I (interquartile range 13.9-29.0 pg/1).
Author: Harvey Clewell, Yu-Mei Tan, and Melvin Andersen
Title: Simulation Modeling of PFAA Exposure and Pharmacokinetics
Affiliation: The Hamner Institutes for Health Sciences, 6 Davis Drive, RTP, NC 27709
Abstract:
Determining the relationship between exposure to PFOA and measured concentrations in plasma
has been hindered by the lack of pharmacokinetic data in humans. For convenience, the
pharmacokinetics of PFOA has 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
DEQ-CFW 00000879

limited, saturable processes must be involved in the kinetic behavior of these compounds. We
have developed a biologically motivated model for PFOA in the monkey and rat, and have
performed an initial extrapolation of this model to the human. This presentation will describe the
alternative approaches for modeling PFOA (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.
Author: Hugh A. Barton
Title: Pharmacokinetic Modeling of PFAA
Affiliation: US EPA, ORD, National Center for Computational Toxicology
Research Triangle Park, NC 27711
Abstract:
Perfluorooctanoic acid (PFOA) has pharmacokinetic properties that appear consistent with a
number of processes that are currently not well understood. Studies in mice exposed orally at
lower doses (1 and 10 mg/kg) demonstrated blood, liver, and kidney concentration time courses
consistent with a one -compartment model, although the tissue distribution is clearly not uniform.
Blood time course concentrations following a single 60 mg/kg oral dose were consistent with a
two -compartment model. Repeated exposures (20 mg/kg/day for 7 and 17 days) produced
exposures inconsistent with the one -compartment predictions, but reasonably predicted by the
two compartment fit based upon the single high dose. I he three -compartment saturable
resorption model can be parameterized to fit all the blood time course data. A more complex
physiologically based pharmacokinetic model would be required to predict the tissue distribution
characteristics. Improved knowledge of the biological processes controlling the pharmacokinetics
of these compounds will better inform cross -species extrapolation and understanding of mode of
action. (This abstract does not present Agency policy).
Author: Christopher Lau, Kaberi Das, Julie Thibodeaux, Brian Grey and John Rogers
Title: Comparative Description of PFAA Developmental Toxicity: An update
Affiliation: RTD, NHEERL, ORD, US EPA, Research Triangle Park, NC
Abstract:
The perfluoroalkyl acids (PFAAs) are a family of fluorocarbons consisting of a perfluorinated
carbon tail (typically 4-12 carbons in length) and an acidic functional moiety, usually carboxylate
or sulfonate. These compounds have excellent surface tension reducing properties and have
numerous industrial and consumer applications. The rates of PFAA elimination and their body
burden accumulation appear to be dependent on carbon -chain length, functional moieties, and
animal species. For instance, in rodents, the serum half-life for the C-8 compounds
perfluorooctane sulfonate (PFOS) was estimated as 7 days (rats) and perflurorooctanoate
(PFOA) as 17-19 days (mice), but that for the C-4 compound perfluorobutyrate (PFBA) was only
2-17 hours (rats and mice). Correspondingly, a slightly longer half-life for the C-9 compound
perfluorononanoate (PFNA), than that of PFOA has been reported in the rat. When laboratory
rodents were exposed to some PFAAs during pregnancy, adverse developmental effects were
noted. Generally, in utero exposure to PFAAs did not produce anatomical defects, except at high
doses where maternal toxicity was observed. However, newborn rats and mice exposed to
PFOS showed labored breathing and died within hours to days, in a dose -dependent manner.
Neonatal mortality was also observed in mice exposed to PFOA, but the rate of loss was less
abrupt than that seen with PFOS, with death reported as late as 3-5 postnatal days of age.
Deficits of growth and development were evident in the neonates exposed to lower doses of the
chemical. Preliminary results from a recent study indicated that mouse neonates exposed to
PFNA displayed a similar pattern of mortality as that seen with PFOA. However, pup loss was
much more gradual, with pups dying until weaning at postnatal day 24. Significant growth deficits
DEQ-CFW 00000880

and developmental delays were noted among survivors, and significant increases in liver weight
were observed up to 6 weeks postnatally. In contrast to the C-8 and C-9 compounds, in utero
exposure to PFBA did not lead to any neonatal death or growth deficits, although slight
developmental delay and transient liver enlargement were seen in the pups. Thus,
developmental toxicity of PFAAs appears to be correlated to the carbon -chain length (with a
potency ranking of PFNA > PFOA = PFOS >> PFBA), and is, to a large extent, related to the rate
of elimination of the chemical. This abstract does not necessarily reflect US EPA policy.
Author: Suzanne E. Fenton, Jason P. Stanko, Sally S. White, and Erin P. Hines
Title: Latent Effects of PFAA Exposure During Perinatal Development.
Affiliation: US EPA, ORD, NHEERL, Reproductive Toxicology Division, RTP, NC 27711
Abstract:
Developmental exposure to PFOA is associated with decreased body weight, as well as
increased mortality of newborn mice. These studies address whether prenatal exposure to PFOA
also leads to altered adult weight gain, changes in organ weights, altered reproductive tissue
development, or other adverse latent health effects in mice. The mouse model was chosen for its
similarity to human PFOA elimination by gender. Time -pregnant CD-1 mice were exposed to a
wide dose range of PFOA for these studies (0.01, 0.1, 0.3, and 1 or 5 mg/kg/day). Exposure was
via gavage over multiple days during gestation or via their water supply (5 ppb) pre- and
postnatally. Male and female offspring were evaluated for numerous health related endpoints.
Males were weighed at numerous ages and preputial separation timing was determined. Females
were assessed for timing of vaginal opening, mammary gland development, estrous cyclicity, and
were weighed on a regular basis. Offspring were necropsied at 18 mo. Whole body, liver, spleen,
white abdominal and intrascapular brown fat were collected and weighed. Mammary glands,
various masses or abnormal tissues, and thymuses were collected and fixed in 10% buffered
formalin.
Significant effects on female weight gain were noted. At postnatal day 1 (PND1), the 5 mg/kg
litters weighed significantly less than control animals while animals of all other dose groups were
similar to controls. There were significant increases in both body weight (0.1, 0.3, and 1 mg/kg) at
20-29 weeks of age and intrascapular brown fat weight (1 and 3 mg/kg at 18 months of age) in
the PFOA group when compared to control animals. Liver, spleen, abdominal white fat and liver
to body weight ratio were not significantly different in any of the treatment groups at 18 months. A
subset of the prenatally exposed females was ovariectomized (ovx) at PND21 and followed
concomitantly with the intact animals. The body weights of these ovx animals showed no
significant difference versus intact animals when compared within dose groups. A final group of
age -matched females were gavage dosed as adults (0, 1, 5 mg/kg PFOA) at 8 weeks of age for
17 days and followed out to 18 months. These adult exposed animals showed no significant
increase in body weight and no significant changes in organ or fat weight at 18 months when
compared to controls. Excessive body or tissue weight gain was not noted in males at any life
stage measured. These data demonstrate a low dose and gender -specific effect of
developmental exposure to PFOA on adult weight.
Effects of developmental exposure to PFOA were noted in the mammary gland. Early
development was abnormal in female offspring and full lactational patency was significantly
delayed in dams. Evaluation of mammary gland sections and whole mounts from late life indicate
lesions that appear to be inflammatory in nature and as well as permanent effects of the early
epithelial stunting. Whether the mammary gland and fat deposition have related modes of action
is currently under investigation. (This abstract does not necessarily reflect EPA policy; SSW
funded by EPA CR833237, NIH T32 ES007126.)
DEQ-CFW 00000881

Author: Barbara D. Abbott
Title: Mechanisms of PFAA Toxicity: Involvement of Peroxisome Proliferator Activator Receptor
Alpha (PPARa) Molecular Signals.
Affiliation: Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection
Agency, Research Triangle Park, NC 27511
Abstract:
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of
environmentally persistent perfluorinaled compounds and are found in the serum of wildlife and
humans. PFOS and PFOA are developmentally toxic in rats and mice. Exposure in utero reduces
postnatal survival and growth and delays development. PFOS and PFOA are weak agonists of
PPARa, a causal pathway for induction of hepatocellular carcinoma in rodents. This presentation
addresses the question of whether PPARa is involved in the mode -of -action for PFOA and
PFOS-induced developmental toxicity and discusses the potential for PFAA to activate PPARa in
an in vitro model. In in vivo studies, WT and PPARa KO mice were exposed to PFOA at 0 — 20
mg/kg/day from GD1-17 or PFOS at 0-10.5 mg/kg/day from GD15-17. These studies
demonstrated that PFOA-induced postnatal lethality, growth effects, and delayed eye opening
were dependent on expression of PPARa, but that the effects on early pregnancy loss were
independent of PPARa. However, PFOS-induced neonatal lethality and delayed eye opening
were not dependent on activation of PPARa. Additional studies are required to further define the
modes -of -action for PFOA and PFOS-induced developmental toxicity. In vitro transfected cell
assays were used to evaluate the ability of PFAA of various carbon chain lengths, (both
perfluoroalkyl and sulfonic acids), to activate the ligand binding domain (LBD) of mouse or human
PPARa. Cos-1 cells were transfected with a plasmid containing either the mouse or human
PPARa LBD and a luciferase reporter and incubated with perfluoroalkyl acids of 4, 6, 8, 9 or 10
carbon chain length or perfluorosulfonic acids of 4, 6, or 8 carbon chain length. The
perfluoroalkyl acids were more active than the sulfonic acids. The activity generally increased
with increasing chain length, and PFAAs generally activated plasmid containing the mouse LBD
to a greater degree than the human LBD. While this model is useful for determining the potential
for PFAA to activate mouse or human PPARa, it cannot address whether these compounds
would activate PPARa in a physiological system. In summary, our in vitro studies indicate that
the PFAAs examined have the potential to act via a PPARa mode -of -action and the in vivo
studies confirmed that PFOA, but not PFOS, has a PPARa-dependent mode -of -action for
developmental toxicity in the mouse. Thus, PFAAs with the ability to activate PPARa and
produce similar outcomes, may or may not have the same mode -of -action. It may be necessary
to determine for each PFAA, and possibly for each outcome, whether a PPARa mode -of -action
exists. This abstract does not necessarily reflect US EPA policy.
Author: M.B. Rosen, D.C. Wolf, B.D. Abbott, J.C. Corton, J.E. Schmid, C. R.Wood, K.P. Das,
R.D. Zehr and C. Lau
Title: Developmental Toxicogenomic Studies of PFOA and PFOS in Mice
Affiliation: NHEERL, ORD, US EPA, Research Triangle Park, NC
Abstract:
Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are developmentally toxic
in rodents. To better understand the mechanism(s) associated with this toxicity, we have
conducted transcript profiling in mice. In an initial study, pregnant animals were dosed throughout
gestation with 1-10 mg/kg PFOA. The expression of genes related to fatty acid catabolism was
altered in hoth the fetal liver and Ming. The effects of PFOA were more pronounced in the fotal
liver and included genes associated with a variety of signaling pathways known to be regulated
by PPARa, although non-PPARa-related effects were suggested as well. In a second study, wild -
type (WT) and PPARa-null adult male mice were dosed for 7 days with either 1-3 mg/kg PFOA or
DEQ-CFW 00000882

50 mg/kg WY-14,643 (WY), a known PPARa agonist. In WT mice, PFOA and WY induced
changes consistent with activation of PPARa. PFOA-treated WT mice deviated from those
exposed to WY with respect to genes involved in xenobiotic metabolism, including up -regulation
of Cyp2b10, a gene regulated by the constitutive androstane receptor (CAR). Few changes were
induced by WY in PPARa-null mice, whereas a moderate number of changes were found in null
mice treated with PFOA, including transcripts related to fatty acid metabolism, inflammation,
xenobiotic metabolism, and cell cycle progression. Regulation by other PPAR isoforms could
account for altered expression of genes involved in fatty acid metabolism and inflammation, while
regulation of xenobiotic metabolizing genes was suggestive of CAR activation. Although a dose -
dependent increase in liver weight was evident in both WT and PPARa-null mice exposed to
PFOA, histological evaluation indicated that this increase was not related to hepatocyte
proliferation in null mice. Instead, nonmembrane-bound cytoplasmic vacuoles were observed
which may be evidence of hepatic PFOA accumulation. A third study focused on the effects of
PFOS in the fetal mouse liver and lung since, unlike PFOA, PPARa is not required for neonatal
mortality in PFOS-treated mice. Pregnant mice were dosed with 5 or 10 mg/kg PFOS throughout
gestation. Transcript profiling was conducted on the fetal liver and lung at term, and results
compared to our previous PFOA study. PFOS-dependent changes were primarily related to
activation of PPARa but also included up -regulation of Cyp2b10. No remarkable differences
were found between PFOS and PFOA, although the effects mediated by PFOS were less robust.
PFOA specifically altered the expression of genes related to inflammation and proteasome
biogenesis in the fetal liver, which may reflect greater activation of PPARa by PFOA. These data
do suggest divergent transcriptional responses for PFOS and PFOA. Therefore, PFOS-induced
neonatal mortality may reflect functional deficits related to the physical properties of the chemical
rather than to transcript alterations. In conclusion, the effects of PFOA are predominately
mediated via PPARa, although activation of CAR as well as other nuclear receptors may be
involved. PFOS is also an agonist of PPARa, although the transcriptional response of PFOS at
developmentally toxic doses is less robust than that observed for PFOA. No apparent differences
in transcript profiling were observed to explain the differences in developmental toxicity between
these two compounds. This abstract does not necessarily reflect EPA policy.
Author: Corton JC' , Rosen MB', Lee JS', Ren H', Vallanat B', Liu J2, Waalkes MP2, Abbott BD'
Lau C'..
Title: Evidence for Involvement of Other Nuclear Receptors in PFAA Toxicity Through Genomic
Profiling
Affiliation:'NHEERL, ORD, US EPA, Research Triangle Park, NC; 2National Cancer Institute,
Research Triangle Park, NC.
Abstract: A number of perfluorinated alkyl acids including perfluorooctanoic acid (PFOA) elicit
effects similar to peroxisome proliferator chemicals (PPC) in mouse and rat liver. There is strong
evidence that PPC cause many of their effects linked to liver cancer through the nuclear receptor
peroxisome proliferator-activated receptor alpha (PPARalpha). To determine the role of
PPARalpha in mediating PFOA transcriptional events, we compared the transcript profiles of the
livers of wild -type or PPARalpha-null mice exposed to PFOA or the PPARalpha agonist WY-
14643 (WYI After 7 rlavc of PYnnC11rA AFi% nr AA 7% of tha nanac nitPrari by PFOA nr WY
exposure, respectively were dependent on PPARalpha. The PPARalpha-independent genes
regulated by PFOA included those involved in lipid homeostasis and xenobiotic metabolism.
Many of the lipid homeostasis genes including acyl-CoA oxidase (Acox1) were also regulated by
WY in a PPARalpha-dependent manner. The increased expression of these genes in
PPARalpha-null mice may be partly due to increases in PPARgamma expression upon PFOA
exposure. Many of the identified xenobiotic metabolism genes are known to be under control of
the nuclear receptor CAR (constitutive activated/androstane receptor) and the transcription factor
Nrf2 (nuclear factor erythroid 2-related factor 2). There was excellent correlation between the
transcript profile of PPARalpha-independent PFOA genes and those of activators of CAR
including phenobarbital and 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) but not
DEQ-CFW 00000883

those regulated by the Nrf2 activator, dithioi-3-thione. These results indicate that PFOA alters
most genes in wild -type mouse liver through PPARalpha, but that a subset of genes are regulated
by CAR and possibly PPARgamma in the PPARalpha-null mouse. The implications of these
studies to the mode of action of PFOA-induced liver tumors will be discussed. This abstract does
not necessarily reflect EPA policy.
Author: Jennifer E. Foreman, Prajakta Palkar and Jeffrey M. Peters
Title: Evaluation of PFOA Toxicity by the Humanized PPARa Transgenic Mouse Model
Affiliation: Center for Molecular Toxicology & Carcinogenesis, The Pennsylvania State University,
University Park, PA.
Abstract:
Previous studies have shown that perfluorooctanoic acid (PFOA) can activate peroxisome
proliferator-activated receptor -a (PPARa). However, significant species differences in the effect of
ligand activation of PPARa are also known to exist. Two humanized PPARa transgenic mouse
lines have been generated; one that expresses the human PPARa in the liver and another that
expresses human PPARa in all tissues. Our laboratory has used these mouse models to examine
the effect of PFOA and perfluorobutryate (PFBA) in the liver. Wild -type, PPARa-null and PPARa-
hTg were treated with either PFOA or PFBA for up to 14 days. After 24 hours, significant changes
in gene expression associated with increased lipid catabolism and activation of PPARa were
observed in clofibrate-treated wild -type mice and PPARa-hTg mire hi it not in PPARa-ni ill miry
These changes were not found in mice treated with PFOA. Serum levels of PFOA were 2,3Xvv
lower after 14 days of treatment in the Sv/129 mice used for this study as compared to CD mice
used in other studies. After 14 days of administration, a PPARa-dependent increase in liver
weight was observed in PFOA-treated wild -type mice at high dose (1.0 mg/kg), but did not occur
in similarly treated PPARa-null or PPARa-hTg mice. Interestingly, an increase in liver weight was
observed in PFBA-treated wild -type mice and was modestly attenuated in PPARa-hTg mice, but
did not occur in similarly treated PPARa-null mice. A PPARa-dependent increase in mRNAs
encoding enzymes involved in fatty acid catabolism was detected by microarray analysis and
confirmed by gPCR in wild -type and PPARa-hTg mice treated with PFOA. Increased expression
of CYP3A4 and CYP21310 were also observed in PFOA-treated mouse liver from all genotypes.
Results from this work demonstrate that PFOA can modulate similar changes in gene expression
required to facilitate fatty acid catabolism via activation of both the mouse and human PPARa. In
contrast, the mild hepatomegaly induced by PFOA is differentially modulated by mouse versus
human PPARa. These results also suggest that other receptors including CAR and PXR may also
be important in modulating liver -specific effects resulting from PFOA exposure.
Recent work has also established that PPARa is required to mediate PFOA-induced post -natal
lethality. Studies are currently underway to examine whether Wy-14,643 and clofibrate can cause
similar post -natal lethality, and whether there is a difference in this response when the human
PPARa is expressed rather than the mouse PPARa. Preliminary results from these studies will be
summarized.
Author: JC DeWitt,' CB Copeland,Z MJ Strynar3, and RW Luebke'
Title: Immunotoxic Potentials of PFOA
Affiliation: 'Curriculum in Toxicology, UNC Chapel Hill, NC; 21mmunotoxicology Branch,
ETD/NHEERL/ORD, US EPA, RTP, NC; 3Methods Development and Application Branch,
HEASD/NERL/ORD, US EPA
Abstract:
Reports of immunomodulation by perfluorooctanoic acid (PFOA) suggest that adaptive immunity
and lymphoid organ weights arP sl lsreptihle to PFOA exposure. Spleen weights, thymus weights,
and primary antibody responses to a T cell -dependent antigen were suppressed in mice exposed
to PFOA for 15 days in the diet or in drinking water at 30 mg/kg body weight (bw). Additional
DEQ-CFW 00000884

studies identified a LOAEL for suppression of primary antibody responses of 3.75 mg PFOA /kg
bw after 15 days of exposure via drinking water. The LOAEL was associated with a PFOA serum
concentration of 7.5 x 104 ng/mL, which is a concentration approximately 150-fold higher than
those measured in environmentally and occupationally exposed humans. PFOA immunotoxicity
may be mediated by the peroxisome proliferator activated receptor alpha (PPARa) as lymphoid
tissues of mice deficient in PPARa (KO) were reported to be less susceptible to PFOA than wild -
type (WT) mice. However, our recent work has demonstrated that changes in adaptive immunity
following PFOA exposure are not exclusively dependent on the presence of PPARa and are
influenced by host phenotype. Primary antibody responses to a T-dependent antigen were
suppressed approximately 15% compared with controls in C57BL/6 WT and PPARa KO female
mice given 30 mg PFOA/kg bw in drinking water for 15 days. Conversely, primary antibody
responses to a T-dependent antigen were not altered compared with controls in Sv129 WT and
PPARa KO female mice exposed at the same dose and for the same duration. In addition to the
influence of PPARa and host phenotype, it has been suggested that primary antibody
suppression from PFOA exposure is mediated by stress -induced corticosterone release. However,
adrenalectomized C57BL/6 WT female mice given 15 mg PFOA/kg for 10 days in drinking water
had suppressed primary antibody responses to a T-dependent antigen that were statistically
equivalent to the suppression observed in sham -operated mice exposed to the same dose and
for the same duration. These studies suggest that adaptive immunity is susceptible to PFOA
exposure, but that the mechanisms by which PFOA affects adaptive immunity are not directly
mediated by receptor activation nor by corticosterone release.
Author: M.M. Peden -Adams""""", D.E. Keil',T. Romano4, M.A.M. Mollenhauer 1,3, D.J. Fort'.
P.D. Guiney7, M. Houde8, K. Kannan9, D.C. Muir8, C.D. Rice10, J. Stuckey", A.L. Segars12, T.
Scott13, L. Talent14, G.D. Bossart15, P.A. Fair", J.M. Keller"
Title: Health Effects of Perfluorinated Compounds- What are the Wildlife Telling Us?
Affiliation: 'Department of Pediatrics, 2Marine Biomedicine and Environmental Science Center,
and the 3Molecular and Cell Biology Program, Medical University of South Carolina, Charleston,
SC, USA; 4Mystic Aquarium and Institute for Exploration, Mystic, CT, USA; 5Clinical Laboratory
Science, University of Nevada —Las Vegas, Las Vegas, NV, USA; 6Fort Environmental, Stillwater,
OK, USA; 7S.C. Johnson and Son, Inc. Racine, WI, USA; 8Environment Canada, Burlington, ON,
Canada; 9Wadsworth Center, New York State Department of Health and Department of
Environmental Health and Toxicology, State University of New York at Albany, Alban, New York,
USA; 10Department of Biological Sciences, Clemson University, Clemson, SC, USA; 'trice
Marine Lab, College of Charleston, Charleston, SC, USA; 12South Carolina Department of Natural
Resources, Charleston, SC, USA; 13Department of Animal and Veterinary Science, Clemson,
University, Clemson, SC, USA; 14Department of Zoology, Oklahoma State University, Stillwater,
OK, USA; 15Harbor Branch Oceanographic Institute, Ft. Pierce, FL, USA; 16NOAA/NOS/CCEHBR
Charleston, SC, USA; 17National Institute of Standards and Technology, Hollings Marine
Laboratory, Charleston, SC, USA.
Abstract:
It has long been said that wildlife often give us the first indication of problems in the environment
that may, if left unchecked, laari to rlalatariniic affar_.t_ in varinim species with subsequent impacts
on human health. From examples with pesticides and raptors to alligators and endocrine
disruption, wildlife has often heralded a problem in an ecosystem. Much work over the last 7
years has documented levels of perfluorinated compounds (PFCs) from multiple species
worldwide. Few studies have, however, assessed the effects of perfluorinated compounds on
health or toxicity in species other than traditional laboratory models. Several studies began
assessing health effects of PFCs in wildlife and lab models in 2003. These models include field
studies with loggerhead turtles and bottlenose dolphins and lab studies with the Western fence
lizard (as a surrogate for sea turtles), white leghorn chickens (as a surrogate for coastal
waterfowl) and rodent models (as a surrogate for bottlenose dolphins and humans). Lab studies
utilized environmentally relevant concentrations that were reported in the literature or measured
DEQ-CFW 00000885

in the field. Previously available studies that assessed only gross toxicological effects such as
weight loss and death, reported effects only at exposure levels above what is documented in
humans and wildlife suggesting that there would likely be no adverse effects from environmentally
relevant exposures. These new studies, however, indicate that PFCs can cause sublethal effects
at environmental concentrations. In relation to clinical health parameters, studies with loggerhead
sea turtles (Caretta caretta) demonstrated positive correlations between the liver enzyme
aspartate aminotransferase (AST) and both perfluorooctane sulfonate (PFOS) and sum total
PFCs. This suggests that these compounds may contribute, either directly or indirectly, to
increased plasma AST levels; thereby, indicating liver dysfunction. Similar increases in AST as
well as alanine aminotranferease (ALT) were observed in the fence lizard (Sceloporus
occidentalis) at PFOS exposure levels comparable to the sea turtles (0.00357 mg/kg/day = 0.1
mg/kg total dose). The correlation and trends in liver enzymes in the two reptile species were not
completely unexpected as previous studies reported increased plasma AST levels in rats
following exposure to 20 ppm PFOS. But these observations were surprising given the PFOS
exposure range of 10 to 100 ppb. Additionally, dosing studies in the lizards confirmed correlative
associations in the loggerhead turtles between PFOS and markers of immune function such as
lysozyme activity and T-cell proliferation. In bottlenose dolphins (Tursiops truncatus) studied in
the summer of 2003, absolute numbers of lymphocytes, numbers of CD4+, CD21+ and CD19+
cells, B-cell proliferation, and C-reactive protein levels were positively correlated with plasma
concentrations of PFOS. However, plasma lysozyme activity and cortisol was negatively
correlated with PFOS levels. NK cell activity, T-cell proliferation, AST, and ALT did not correlated
with PFOS concentrations in the dolphins. In B6C3F1 mice exposed to PFOS concentrations
measured in dolphins, these effects were not observed nor were aiterations in liver enzymes as
has been reported at much higher doses in mammalian models. In ovo chicken (Gallus gallus)
studies resulted in no decrease in hatch rate, while chicks exhibited increased liver (2.5 and 5 mg
PFOS/kg egg wt) and spleen weights (1, 2.5 and 5 mg PFOS/kg egg wt). At the 5 mg PFOS/kg
treatment, body length (crown -rump length) was increased compared to control. For all three
treatment groups lysozyme activity was increased while no significant effect was seen in antibody
titers, or thymic or splenic T-cell populations. In utero PFOS exposure in mice resulted in
decreased NK-cell activity and antibody production. In adult mice, decreases in IgM antibody
production were seen at plasma PFOS levels similar to those found in wildlife and humans.
Studies in the South. African clawed frog (Xenopus laevis) indicate that PFOS may be anti -
estrogenic which appears to be supported by rodent PFOS exposure studies. Although much still
needs to be understood about the mechanism by which these effects occur and how that
mechanism differs between species, these studies clearly indicate that PFCs can alter health
parameters at environmentally relevant levels.
Author: J. Jackson Ellingtona, John W. Washingtonb'a, John J. Evansb'a, Thomas M. Jenkinsb,a
Sarah Hafner°
Title: Method Development for the Determination of Fluorotelomer Alcohols in Soils by Gas
Chromatography Mass Spectrometry
Affiliation:'USEPA, National Exposure Research Laboratory
960 College Station Road, Athens, GA 30605, bSenior Service America, Inc., 'Student Service
Authority,
Abstract: Fluorotelomer alcohols (FTOHs) have been widely studied as precursors to
perfluorocarboxylates, e.g. 8:2 FTOH degrades to perfluorooctanoic acid (PFOA). This
presentation describes an analytical method for the extraction and analysis of 6:2, 8:2, and 10:2
FTOHs. Gas chromatograph/chemical ionization -mass spectrometry (GC/CI-MS) was used for
sensitive determination of the fluortelomer alcohols. The best selectivity and sensitivity was
observed when the detector was operated in the positive mode (GC/PCI-MS). Alcohol levels in
the methyl tertiary butyl elher (MTBE) extracts of soils were determined based on the retention
times of standards and the response of the protonated molecular ions [M + H]+. In fortified soils
the peaks in the PCI chromatogram assigned to FTOHs were confirmed by treatment of the
extract with a silylation reagent through observing the loss of the FTOH peaks and the
DEQ-CFW 00000886

appearance of trimethylsilyl (O-TMS) peaks. The instrument detection limit (IDL) was 0.016,
0.010, and 0.014 pg/uL for 6:2, 8:2, and 10:2 FTOH, respectively. The method detection limit
(MDL) depended on the soil matrix but was as low as 0.05 pg/g.
Author: Zhishi Guo', Xiaoyu Liu', Kenneth A. Krebs', and Nancy F. Roache2
Title: Testing of PFAA Release from Aged Articles of Commerce
Affiliation:'APPCD, NRMRL, ORD, U.S. EPA, Research Triangle Park, NC and 2Arcadis,
Research Triangle Park, NC
Abstract:
Products such as fluoropolymer-coated cookware, plenum cable, thread sealant tape,
membranes for apparel, surface protective coatings for paper, textile, and carpet may contain
PFOA or its precursors (e.g., fluorotelomers). OPPT needs to understand whether these products
play a significant role in human exposure to PFOA in the indoor environment. Although progress
has been made in some areas including toxicity, sources, transport, transformation, and
distribution in the environment, it is not fully understood how the general public gets exposed to
these chemicals. It is known that consumer articles containing or treated with fluorinated
chemicals can be a source of PFOA. Given that consumer articles are used in either close vicinity
of or direct contact with humans, it is important to evaluate the source strengths and ways by
which PFAAs are released. The main goals of this project are to characterize the source and
transport of PFAA in the indoor environment and the factors that may affect PFAA release from
consumer articles.
In the source study, over 100 consumer articles were collected from the open market. They were
analyzed for the content of eight (C5 to C12) perfluoroalkyl acids (PFCAs). The results are used
to identify the PFAA sources potentially important to human exposure. It was observed that the
market has been in a transition period. While consumer articles with high PFAA content are still
on the market, some manufacturers of fluorinated chemicals have re-formulated their products to
reduce the PFAA content, and in some applications, fluorinated chemicals have been replaced by
non -fluorinated chemicals. The trends are uneven, however. Furthermore, given that the
consumer articles are made in many countries, an international collaboration is needed to further
reduce the PFAA content.
In the currently on -going transport study, accelerated aging tests will be conducted to determine
whether PFAA release from the source through gas -phase transfer is significant. Tests will be
conducted based on the principles of ASTM standard guide 5116. Additional tests will be
conducted in large environmental chamber (ASTM standard guide 6670) or research house to
determine whether particle re -suspension plays any role in human exposure. PFAA release under
normal use conditions for certain types of articles, such as apparel and dental floss will also be
tested.
The results of this research project will help better understand the sources of PFAAs to which the
general population is exposed and the potentially important exposure routes in the indoor
environment. The findings will help reduce the uncertainty in PFAA assessments and
development of risk management solutions.
DEQ-CFW 00000887

Author: Helens Goeden
Title: Issues and Needs for PFAA Exposure and Health Research: A State Perspective
Affiliation: Minnesota Department of Health, St. Paul, MN
Abstract:
The 3M Company (3M) produced perfluorochemicals (PFCs) at its Cottage Grove facility in
Washington County, Minnesota from the late 1940's until 2002. For a time, wastes from the
production process were disposed on site. The water treatment plant on site that processed water
from production activities did not remove PFCs, so PFCs were in the waste water that went into
the Mississippi River. Some sludge left over from the water treatment process also contained
PFCs and was disposed on site. Firefighting foams containing PFCs were also used in training
exercises on -site.
PFCs-containing wastes were also disposed of by 3M off -site at three disposal sites located
within Washington County. A variety of PFCs released from the disposal sites have contaminated
groundwater and drinking water wells in 7 communities, covering an area of nearly 100 square
miles.
In 2004 the Minnesota Pollution Control Agency (MPCA) began evaluating closed and active
landfills that may have accepted PFC containing waste, directed 3M to investigate and cleanup
the various PFC waste disposal sites, and initiated sampling of Mississippi River sediment and
discharge from outfalls at the 3M Cottage Grove facility. MPCA is also investigating PFCs in the
wider environment through statewide sampling of ambient groundwater and surface water. fish
tissue, wastewater treatment plants, and landfills that did not accept 3M waste.
Perfluorobutanoic acid (PFBA) was the most frequently detected PFC in ambient groundwater
and surface water. A wider range of PFCs (perfluorobutane sulfonate (PFBS), perflurohexane
sulfonate (PFHxS), perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA)) were
frequently detected at waste water treatment plants. PFCs, mainly PFBA, PFOA and PFOS, were
detected in the leachate and/or condensate gas at all landfills sampled, including those that did
not accept 3M waste. PFC concentrations in the non-3M related landfills were between one to
three orders of magnitude lower than at sites that accepted 3M waste.
In late 2004 the Minnesota Department of Health (MDH) began sampling public and private water
supplies to investigate possible exposures from past PFC waste disposal. PFBA, PFOA and
PFOS were the most commonly detected PFCs, reaching maximum concentrations in drinking
water of 11.8, 3.2 and 3.4 ug/L, respectively.
Over the last few years the MDH and MPCA have derived health based criteria for a limited
number of PFCs
Groundwater and Drinking Water
7 ug/L PFBA, 0.3 ug/L PFOA, and 0.3 ug/L PFOS
Surface Water
Mississippi River Pool 3
0.72 ug/L PFOA and 0.006 ug/L PFOS
Lake Calhoun
0.61 ug/L PFOA and 0.0122 ug/L PFOS
Fish Advisory
1 meal/week
> 40 ng/g PFOS
1 meal/month
> 200 ng/g PFOS
Soil Screening Values
Residential Land Use
77 mg/kg PFBA, 2 mg/kg PFOA, and 2 mg/kg PFOS
Industrial Land Use
500 mg/kg PFBA, 13 mg/kg PFOA, and 14 mg/kg PFOS
DEQ-CFW 00000888

The MDH and MPCA are continuing to expend resources on evaluating PFCs in the environment.
On -going activities include expansion of environmental media sampling, air and precipitation
monitoring, foodweb study, source identification study, PFC product substitution, and treatability
studies. EPA is assisting Minnesota in evaluating the extent and magnitude of PFC
contamination in fish throughout the state.
Health based criteria for additional PFCs (such as PFBS, PFHxS and PFHxA) are needed in
order to provide health based advice to citizens who are exposed to contaminated environmental
media. Derivation of these values is based on knowledge regarding toxicity and exposure. Data
identifying relevant adverse health effects, life stage sensitivities, and toxicokinetic are essential
to evaluate toxicity potential. Understanding potential sources and routes of exposure are critical
for risk management decisions. The generation of this type of data is typically beyond the
resources of individual state agencies. Increased communication and cooperation between EPA
and state agencies can improve our ability to deal with emerging contaminant situations such as
PFCs and meet our common goal of protecting human health and the environment.
DEQ-CFW 00000889

U.S. EPA FFAA Days ii Workshop - Fosters
P-1 Elevated Levels of Perfluorochemicals in Plasma of New York State Personnel
Responding to the World Trade Center Disaster
LIN TAO', KURUNTHACHALAM KANNANt`, KENNETH M. ALDOUS',
MATTHEW P. MAUER', AND GEORGE A. EADON'
'Wadsworth Center, New York State Department of Health and Department of
Environmental Health Sciences, State University of New York at Albany, Empire State Plaza, PO
Box 509, Albany, New York 12201-0509, USA
$Bureau of Occupational Health, Center for Environmental Health, New York State Department of
Health, 547 River Street, Troy, NY 12180, USA
The collapse of the World Trade Center (WTC) on September 11, 2001 resulted in the release of
several airborne pollutants in and around the site. Perfluorochemicals including
perfluorooctanesuifonate (PFOS) and perfiuorooctanoic acid (PFOA), which are used in soil and
stain resistant coatings on upholstery, carpets, leather, floor waxes, polishes, and fire -fighting
foams were potentially released during the collapse of the WTC. In this pilot study, we analyzed
457 plasma samples of New York State (NYS) employees and National Guard personnel
assigned to work in the vicinity of the WTC between September 11 and December 23, 2001, to
assess exposure to perfluorochemicals released in dust and smoke. he plasma samples
collected from NYS WTC responders were grouped based on estimated levels of exposure to
dust and smoke, as: more dust exposure (MDE), less dust exposure (LDE), more smoke
exposure (MSE), and less smoke exposure (LSE). Furthermore, samples were grouped, based
on self -reported symptoms at the time of sampling, as: symptomatic and asymptomatic. Eight
perfluorochemicals were measured in 457 plasma samples. PFOS, PFOA,
perfluorohexanesulfonate (PFHxS), and perfluorononanoic acid (PFNA), were consistently
detected in almost all samples. PFOA and PFHxS concentrations were approximately two fold
higher in WTC responders than the concentrations reported for the US general population. No
significant difference was observed in the concentrations of perfluorochemicals between
symptomatic and asymptomatic groups. Concentrations of PFHxS were significantly (p 50.05)
higher in the MDE group than in the LDE group. Concentrations of PFNA were significantly
higher in the MSE group than in the LSE group. Significantly higher concentrations of PFOA and
PFHxS were found in individuals exposed to smoke than in individuals exposed to dust. A
significant negative correlation existed between plasma lipid content and concentrations of certain
perfluorochemicals. Our initial findings suggest that WTC responders were exposed to
perfluorochemicals, especially PFOA, PFNA, and PFHxS, through inhalation of dust and smoke
released during and after the collapse of the WTC. The potential health implications of these
results are unknown at this time. Expansion of testing to include all archived samples will be
critical to help confirm these findings. In doing so, it may be possible to identify biological markers
of WTC exposure and to improve our understanding of the health impacts of these compounds.
P-2 Pilot Study of Serum Biomarkers of Polyfluoroalkyl Compounds in Young Girls
Susan M. Pinney', Frank M. Biro2,3, Lusine Yaghjyan', Cendi Dah13, M. Kathrr BrownAnn
Hernick', Gayle Windham¢, Antonia Calafat5, Kathy Ball', Lawrence H. Kushi , Robert
Bornschein'
'University of Cincinnati College of Medicine, Dept. of Environmental Health, Cincinnati, OH,
zUniver University of Cincinnati College of IMedl Vll le, Dept. of PGdlatrlls, ^ill ll,lnl-1 iitl, v^H, tJSA
USA; ;
3Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; 4Division of Environmental
and Occupational Disease Control, California Department of Public Health, Richmond, CA, USA;
5Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease
Control and Prevention, Atlanta, GA, USA; 6Division of Research, Kaiser Permanente, Oakland,
CA, USA.
DEQ-CFW 00000890

Background: Polyfluoroalkyl compounds (PFCs) and their salts, such as perfluorooctanoate
(PFOA) and perfluorooctane sulfonate (PFOS), are chemicals that have wide consumer and
industrial applications and known environmental persistence. PFCs have been detected in
humans and wildlife, and health effects have been noted in laboratory animals, including changes
in mammary gland structure and function.
Objective/Hypothesis: Within the NIH Breast Cancer and the Environment Research Centers
(BCERC), we conducted a pilot study of multiple environmental biomarkers in young girls (age 6-
8 years), including PFCs, followed by a second study at the Ohio site where elevated levels of
PFOA had been detected in the pilot study.
Methods: Participants for the pilot study were recruited from area schools in Cincinnati and
Northern Kentucky (n=27) and membership of the Kaiser Permanente health maintenance
organization in the San Francisco Bay area (N=28). Blood was collected using a standard
protocol and materials provided by the Centers for Disease Control and Prevention (CDC), and
assayed for the perFluoroalkyl acids using high-performance liquid chromatography -tandem mass
spectrometry.
Results: Four of the seven PFCs, including PFOA and PFOS, were detected in all samples, and
only one was detected in less than 70%. The median values for PFOA differed by site (PFOA -
12.9 ng/ml for California and 20.2 ng/ml for Greater Cincinnati), an unexpected finding.
Within the Ohio site, 14 of the 15 girls in one community had PFOA values above the NHANES
1999-2000 951h percentile value for children 12-19 years (11.2 ng/ml, Calafat, 2007). In the
follow-up study of 42 girls from the community with higher values, the elevation in serum PFOA
persisted (median 17.4 ng/ml, range 6.9-42.6 ng/ml serum), with 31 having values above the
NHANES 95'h percentile. For the subset of girls from greater Cincinnati who were in both the pilot
and second study, the pilot serum samples were reanalyzed with the second study samples. The
difference between PFOA measures for each girl, one year apart, was a median decrease of 7.9
ng/ml for girls in the community with the higher values (p<0.0001 under a one sample t-test with
Ho=O) and a median decrease of 1.6 ng/ml (p<0.001) for the girls from the community with the
lower values.
Conclusions: Sufficient between -person variation in PFC levels exists to enable an investigation
of association with age of onset of pubertal maturation. The elevated serum PFOA levels in one
community in the greater Cincinnati areas appear to be decreasing, but cannot be linked to a
source at this time. Further research is required to identify the source and potential health effects.
Calafat A., Kuklenyik Z., Reidy J., Caudill S., et al. Serum concentrations of 11 polyfluoroalkyl
compounds in the US population: Data from the National Health and Nutrition Survey (NHANES)
1999-2000. Environ. Sci. Technol. 2007; 41(7):2237 — 2242.
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), and to the University of California San Francisco Bay
Area Breast Cancer and the Environment Research Center (U01 ES012801). We also
acknowledge the biostatistical expertise of Paul Succop, and geocoding assistance of Patrick
Ryan.
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.
DEQ-CFW 00000891

P-3 PFOS and PFOSA in Bottlenose Dolphins: An Investigation Into Two Unusually
High Mortality Epizootics
Douglas Kuehl', Romona Haebler2, Charles Potter 3, Garet Lahvis4,
Michael Donahue5 and Ronald Rega15
' Mid -Continent Ecology Division, National Health and Environmental Effects Research
Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth,
MN, 55804 [e-mail]
2 Atlantic Ecology Division, National Health and Environmental Effects Research, Office of
Research and Development, U.S. Environmental Protection Agency, Narragansett, RI 02882
[e-mail]
3 Museum of Natural History, Smithsonian Institution, Washington, D.C. 20562
4 Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR
97239
5 Department of Mathematics and Statistics, University of Minnesota -Duluth, Duluth, MN 55812
Along the Atlantic coast of the United States during 1987 and 1988, bottlenose dolphins (Tursiops
truncates) suffered one of this country's largest marine mammal mass mortality events. An
estimated 50% of all near -shore bottlenose died during this short period. Two years later a
second, although less dramatic, event occurred along the United States coastline of the Gulf of
Mexico. The cause of these mortalities is not known for certain; however, morbilliviral infection
seemed to have spread rapidly throughout the dolphins. Suppression of the animal's immune
system by high concentrations of chemical contaminants was suggested as a contributing factor.
III uider to investigate this hypothesis, we determined by GC/MS the concentration of many
polychlorinated and polybrominated chemicals, such as PCBs, chlorinated pesticides, and
brominatcd flame retardants, as well as mercury, determined by AA, in the affected animals. The
development of electrospray ionization LC/MS has now allowed us to re-examine these same
dolphin tissues (liver) for the presence of PFOS and a metabolic precursor of PFOS, PFOSA.
Concentrations of PFOS in the affected bottlenose were found to be greater than, and statistically
different from those found in other species not affected during the epizootics, and to other
bottlenose dolphin populations. PFOS concentrations were found to be as great as, or greater
than, concentrations of PCBs, thirteen chlorinated pesticides, and PBDPEs. PFOS concentrations
were generally less than mercury residues. PFOS was found to be readily transferred in utero
from mother to fetus.
P-4 Identification of a Major Source of Perfluorooctane Sulfonate (PFOS) at a
Wastewater Treatment Plant in Brainerd, Minnesota
James Kelly, M.S., Minnesota Department of Health, and Laura Solem, PhD, Minnesota Pollution
Control Agency, St. Paul, MN.
Perfluorooctane sulfonate (PFOS) is a globally distributed persistent contaminant in
environmental and biological media. Due to the history of perfluorochemical (PFC) manufacture
and waste disposal in the state, the state of Minnesota has been evaluating the presence of
PFCs in drinking water and fish. PFOS has been shown to bioaccumulate in fish tissue, and the
detection of elevated concentrations of PFOS in fish in a number of lakes and rivers in Minnesota
has resulted in the issuance of PFOS-based fish consumption advice in some instances. While
PFC waste disposal sites have been identified as one potential source, currently, little is known
about other source(s) of PFOS in lakes and rivers in Minnesota.
In 2007, the Minnesota Pollution Control Agency (MPCA) conducted a study of PFCs in influent,
effluent, and sludge at 28 public and private wastewater treatment plants (WWTPs) throughout
Minnesota. Samples of influent (n=32), effluent (n=28), and sludge (n=23) were analyzed for 13
PFCs by Axys Analytical Services, British Columbia, Canada.
Several WWTPs, mainly in urban areas, had elevated levels of individual or multiple PFCs that
could reasonably be attributed to local sources, including known PFC contamination in drinking
water sources or the use of PFC containing products at an industrial facility or airport. A notable
DEQ-CFW 00000892

exception was PFOS in the influent, effluent, and sludge from the City of Brainerd WWTP,
operated by Brainerd Public Utilities (BPU). The plant is located about 135 miles northwest of St.
Paul, and discharges to the Mississippi River. This plant had the highest detections of PFOS in all
three media of any of the wastewater treatment plants tested, with an effluent PFOS level of 1.51
micrograms per liter (pg/L). Samples from wells supplying drinking water to the city of Brainerd
showed no PFCs.
BPU conducted an investigation of the wastewater collection system to identify the source(s) of
the PFOS contamination. The main source (-95%) of the PFOS was identified as a large chrome
plating operation in the city who reported using a legal surfactant product to control hexavalent
chromium emissions. The product reportedly contained "organic fluorosulfonate" between 1 % and
7% by weight.
Samples collected within the plating facility by BPU staff identified the specific points where
PFOS remains in the plating solution tanks. An alternate surfactant product that does not contain
PFOS is currently being used by the facility and levels of PFOS in wastewater from the facility
and the BPU WWTP are expected to drop over time.
The findings of the Brainerd investigation represent the first comprehensive look at PFOS inputs
to a WWTP, and the first documentation of the importance of chrome plating as a possible source
of PFOS in WWTP effluent. Little is currently known about levels of PFOS in agricultural fields
where PFOS-containing sludge from such facilities is applied, and the uptake of PFOS by crops
has not been extensively studied.
P-5 Determination of Perfluorocarboxylic Acids in Sludge
Hoon Yooa,b, John W. Washington b, Thomas M. Jenkins`'b
a Student Service Authority
bUS EPA, National Exposure Research Laboratory,
960 College Station Rd, Athens, GA 30605
Senior Service America, Inc.
Methods were developed for the extraction from wastewater -treatment sludge and quantitation by
LC/MS/MS of perfluorocarboxylic acids (PFCAs, C6 to C12), 7-3 fluorotelomer carboxylic acid (7-
3 FTCA) and 8-2 fluorotelomer 2-unsaturated carboxylic acid (8-2 FTUCA) using LC/MS/MS. In
the last 10 years, advances in analytical instrumentation and techniques have enabled monitoring
studies aimed at documenting the presence of PFCAs in various matrices including human
serums, biological tissues and water bodies. Although these studies have documented the
widespread distribution of PFCAs in numerous environmental matrices, exposure routes of the
PFCAs to the receptors remain unclear. To help address this uncertainty, researchers now have
begun looking for PFCA precursors, such as 8-2 FTUCA, in these matrices as well. Unlike many
organo-chlorine contaminants, which primarily sorb to abiotic solid matrices, PFCAs commonly
tend to partition to the water column in part because of their low dissociation constants and high
water solubility. In sludge, mostly anaerobic bacteria decompose organic contaminants via
enzymatic processes including hydrolysis, oxidation and reduction. In part because of this,
concentrations of PFCAs in sludge, which are considered to be recalcitrant, are expected to be
elevated compared to soils and sediments. In addition, biosolids, the treated form of sewage
sludge, have been permitted for use in land -application programs. This raises concerns over the
impact of bioavailability of PFCAs in land -applied sludge to in -situ vegetation or live -stock. For
these reasons, there is a need to develop protocols for the extraction and determination of
PFCAs and related compounds from sludge and biosolids.
Three extractants were tested to evaluate their efficacies to recover PFCAs and telomer acids
from sludge; 60:40/ACN:H2O, 90:10/MeOH:H20, and MTBE. Test sludge from a New York City
wastewater -treatment plant was settled overnight and supernatant was decanted. Briefly, 1g wet
sludge in a 16-mL PPCO centrifuge tube was spiked with 1ng of 13C5-PFNA as a recovery
internal standard and sonicated in a hot water bath with an addition of 200uL of 2M NaOH for an
hour. Then, an equivalent volume of 2M HCl was added to neutralize the solution. The -sludge
was shaken in 7.5mL of 60:40/ACN:H2O or 90:10/MeOH:H20 for an hour. This slurry was
DEQ-CFW 00000893

separated by centrifugation at 10,000rpm and this extraction step was repeated three times.
Conventional MTBE ion -pairing extraction also was conducted wherein 1g of sludge was mixed
with an ion -pairing agent (2mL TBA mix) and 5mL of MTBE. This mixture was shaken for 30min.
This extraction step was repeated three times and all extractions were combined. In addition, the
effect of an overnight oxidation � pretreatment on PFCA extraction from sludge was tested using
NaOH, HCI, and K2S2O8. Upon completion of the pretreatments, the sludge was extracted with
60:40/ACN:H2O as described above. The extract was dried under an SPE assembly and
reconstituted with 1 mL of 60:40/ACN:H2O containing 13C4-PFOA as a matrix internal standard.
Among the extractants tested, 60:40/ACN:H2O extracted the greatest concentrations of PFCAs
from test sludge, followed by 90:10/MeOH:H20 and MTBE. Pretreatment of NaOH effectively
extracted PFCAs in sludge, but HCI and K2S2O8 were less effective. A NaOH pretreatment
yielded at least three times greater PFCA concentrations than the sludge without a pretreatment.
Disclaimer: Although this work was reviewed by EPA and approved for publication, it may not
necessarily reflect official Agency policy. Mention of trade names or
commercial products does not constitute endorsement or recommendation for use.
P-6 Results from a Study on the Biodegradation Behaviour of a Clariant Fluorotelomer-
Based Acrylate Polymer Coated on Polyester and Cotton Fabric Under Landfill Simulation
Conditions
1 1 2 2 3
Volker Koch , Wolfgang Knaup , Henrich Roeper , Rainer Steqmann , Silke Fiebiq , Thomas
3 3
Geffke ,DirkSchulze
1 2 3
Clariant Products (Germany) GmbH, Hamburg University of Technology Germany, Noack
Laboratories Germany
Fluorotelomer-based substances like 8-2 Fluorotelomer alcohol (2-Perfluorooctylethanol) are
speciality chemicals being used to synthesize e.g. high molecular weight Fluorotelomer-based
acrylate polymers (FBAPs). FBAPs are used for coating of textiles, paper and carpet to achieve
oil, stain and water repellency properties. Concerns that fluorotelomer-based polymers may be a
source for low molecular Fluorote lomer-based substances which could be transformed to
perfluorinated carboxylic acids like PFOA have triggered investigations on the biodegradation
potential of a commercial FBAP coated on Polyester and Cotton Fabric under landfill conditions.
Due to the long residence time of waste in a landfill and the unknown sources of the waste the
degradation behaviour of FBAPs in a municipal landfill is difficult to study. Instead a Landfill
Simulation Study has been set up using artificial waste which is representative for the waste
composition of municipal solid waste being dumped on American landfills today. Experimental set
up of the Landfill Simulation and results are reported.
P-7 Biodegradation Kinetic and Estimated Half -Life of a Clariant Fluorotelomer-Based
Acrylate Polymer — Results from a Test on Aerobic Transformation in Soil
1 1 2 2 2
Volker Koch , Wolfgang Knaup , Silke Fiebig , Thomas Geffke , Dirk Schulze
Clariant Gerrnany, Noack Laboratories Germany
Fluorotelomer-based substances like 8-2 Fluorolelorner alcohol (2-Perfluorooctylethanol) are
speciality chemicals being used to synthesize e.g. high molecular weight FlLie rote lomer-based
acrylate polymers (FBAPs). FBAPs are used for coating of textiles, paper and carpet to achieve
oil, stain and water repellency properties. Concerns that fluorotelomer-based polymers may be a
source for low molecular Fluorotelomer-based substances which could be transformed to
peifluuiiiraled carbuxylic acids like PFOA Iiave triggered invesligatlons on the biodegradation
potential of a purified FBAP in aerobic soil. The PFOA measured in soil during this test on
Aerobic Transformation may be residual PFOA in the FBAP and PFOA formed from degradation
DEQ-CFW 00000894

st
of the FBAP as well as from degradation of 8-2 Fluorotelomer alcohol. A three component 1
- order kinetic model allows to attribute the origin of PFOA in the soil and the estimation of the half-
life of 8-2 Fluorotelomer alcohol as well as the half-life of the Fluorotelomer-based acrylate
polymer (FBAP).
P-8 Determination of Perfluorinated Compounds in Surface Soils
Mark Strynar', Shoji Nakayama 2, Larry Helfant3, Andrew Lindstrom'
'U.S. Environmental Protection Agency, National Exposure Research Laboratory, North Carolina,
USA
2Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA
3Senior Environmental Employment Program, NCBA, North Carolina, USA
Much attention has recently been focused on the investigation of perfluorinated compounds
(PFCs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and other
related homologues. A growing number of studies have demonstrated the widespread presence
of PFCs in environmental and biological matrices. However, little has been done to date to
characterize the environmental distributions of these compounds at the local, regional, or world-
wide scales. Surface soils are an easily acquired matrix that can be used to evaluate patterns of
PFC contamination. Moreover, soils are intricately linked with hydrologic and atmospheric cycling,
both of which have been shown to be important factors in the distribution and fate of the PFCs.
Recent evidence for transport of PFCs from a manufacturing facility to nearby soil and water has
been demonstrated. In addition, consumption of PFC contaminated water has been shown to
increase the body burden of individuals drinking that water. The net negative charge of soils and
negative charge of the more common PFCs acids and sulfonates may lead to mobility through
soils to ground water. Little to no information exists concerning the translocation of PFCs from
contaminated soils into plant matter. Few studies have investigated the analysis of PFCs in soils,
but given the central role that soil is likely to play in the contamination of water and food supplies,
a well characterized analytical method for PFCs in soils is a very high priority. A new method has
been developed for the analysis of 10 related PFCs in surface soils at the sub ng/g concentration
range. This method involves ultrasonic extraction of soils in methanol followed by a graphitized
carbon SPE cleanup and LC/MS-MS analysis.
Surface soils were obtained from various sources world-wide and stored at 4°C prior to being
sieved to 2 mm at field moisture before analysis. Sub -samples were extracted with methanol via
shaking and sonication. Extracts were then subjected to cleanup using SPE (graphitized carbon).
The final sample eluate was reduced in volume under N2 gas and then injected on a high-
performance liquid chromatography coupled with quadrupole tandem mass spectrometer
(LC/MS/MS) for quantitation. Quantitation was carried out using surface soil/solvents fortified with
a series of PFC standards (6 points). Recoveries were calculated using matrix matched solutions.
Methanolic extracts of soils are inherently dirty due to co -extraction of matrix interferences. The
SPE cleanup with graphitized carbon (GL Sciences, Carbograph) with no modifiers removed
much of the matrix interference and allowed the extracts to be reduced in volume enough to
provide sensitivity and precision in the sub ng/g range. Recovery experiments using solvent
based standards and soils spiked with methanolic PFC standards indicated that SPE cleanup
with graphitized carbon generally lead to recoveries in the range of 70-130%. Duplicate analysis
of soils resulted in coefficients of variation ranging between 2.2 — 15.1 % at spike levels of 50 and
200 pg/g soil. Extraction of between 2-5 grams of soils appeared to be adequate for
determination of low level (sub ng/g) contamination. Application of the method to a soil sub -set
indicates a wide range in concentrations and composition of PFC in these samples. An
assessment of the performance characteristics of this method and application to an international
collection of soils (USA, Japan, China) for PFC analysis will be presented.
DEQ-CFW 00000895

P-9 Analysis of Fish Homogenates for Perfluorinated Compounds
Mark J. Strynar', Xibiao Ye', Andrew Lindstrom', Shoji Nakayama', Laurence Helfant', Jerry
Varns' and James Lazorchak2
Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory,
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, 2 Ecological
Exposure Research Division, National Exposure Research Laboratory, U.S. Environmental
Protection Agency, Cincinnati, OH 45268
Perfluorinated compounds (PFCs) have been manufactured and used in industrial and consumer
applications for more than 50 years. Recent studies have demonstrated that PFCs are
widespread in wildlife and environmental matrices. Due to the toxicity, persistence, and
bioaccumulation of some PFCs, interest in these compounds is increasing. However, little is
known about the ecological or human exposure effects of PFCs. A pilot scale study was
undertaken to assess PFCs in whole fish homogenates collected as part of the Environmental
Monitoring and Assessment Program (EMAP)-Great Rivers Ecosystem (GRE) project. The EMAP
GRE fish tissue indicator was developed as a means to assess the bioaccumulation of persistent
toxic substances in the environment and to estimate potential exposures at higher trophic levels.
Although whole fish contamination is primarily an indicator of exposures in piscivorous wildlife,
these data are also useful for estimating potential human exposures via this route. In brief, a
subset of 60 whole fish homogenates from 10 sites on each of three major river systems in the
United States (Upper Mississippi, Missouri and Ohio Rivers) were analyzed for PFCs. This
gll .-,et was, cuhiartivaly rhncan f1.rom tha PNAAP-',Pr n1.rnhnhilic+ir rr1neinr of fish h .,,.,no. +o� to
get a spatially representative sample from each of the three rivers. Methods development,
validation data, and preliminary study results will be discussed.
Disclaimer: Although this work was reviewed by EPA and approved for publication, it may not
necessarily reflect official Agency policy.
P-10 Method Development for the Determination of Perfluorinated Organic Compounds
(PFCs) in Surface Water
Shoji F. Nakayama, Andrew B. Lindstrom, Mark J. Strynar, Xibiao Ye, Laurence Helfant, Jerry
Varns.
Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory,
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Perfluorinated organic compounds (PFCs) have been manufactured world wide and used for
more than 50 years. Concern over these compounds is due to recent studies showing some
PFCs are toxic, carcinogenic, bioaccumulative, and persistent. Perfluorooctanoic acid (PFOA)
and perfluorooctane sulfonate (PFOS) are the best known PFCs, but there are a number of other
PFCs that have been produced. Little information has been published about the distribution of
these compounds in the environment or how humans are exposed. The most comprehensive
research is a series of studies from Japan that suggest contamination of surface waters and
related drinking water supplies may contribute to exposure. To determine the environmental
distributions of these materials in the U.S., a method for the determination of the PFCs has been
developed and used to characterise surface water samples from the Cape Fear River Basin in
North Carolina, USA, in the spring of 2006. One litre water samples were collected, spiked with
internal standards, and run through Oasis HLB using a positive pressure loading pump. The
PFCs were then eluted with methanol, concentrated, and analysed via LC/MS/MS equipped with
Wakopak Fluofix column. Quantification for C6—C12 perfluorinated carboxylic acids and C4—C8
sulfonates was performed using a 6-point standard curve prepared with deionised water. To
ensure method precision and accuracy, quality control samples and travel blanks were analysed
simultaneously. The method detection limit was 1 ng/L for all compounds with precision and
accuracy being ±16% and within 100±15%, respectively. These PFCs were found in most
samples with total PFC concentrations ranging from 1.64 to 942 ng/L. The variations in
DEQ-CFW 00000896

concentration and distinctive patterns of the different PFCs found in various parts of the basin will
be discussed.
P-11 Method Development for the Determination of Perfluorinated Compounds in
Human Urine
Shoji F. Nakayama, Mark J. Strynar, and Andrew B. Lindstrom
U.S. Environmental Protection Agency, National Exposure Research Laboratory, North Carolina,
USA
There is increasing research focusing on and public interest in perfluorinated compounds (PFCs),
including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and other structurally
related analogues, primarily because they are bioaccumulative, persistent, and toxic. To explore
the possibility of a non-invasive way to assess human exposures to these materials, a new
method has been developed and evaluated for the quantitation of trace levels of 10 PFCs in
human urine. In preliminary studies using a synthetic human urine analogue, the limit of
quantitation (LOQ) was determined as 1-2 ng/L with precision and accuracy ranging from 5%-
16% and 75%-125%, respectively, for all compounds. The application of this method using
human urine samples will be presented at the conference. The ability to detect and quantify these
compounds in human samples may be a significant new tool for the non-invasive biological
monitoring of PFC exposure. Application of this method in human studies will be of great interest
for physiologically -based pharmacokinetic modelling efforts which are intended to describe the
disposition of these materials in humans. This study is the first report of a method for the
measurement of PFCs in human urine. The lower limit of quantitation (LLOQ) was determined to
be 1-2 ng/L for all targeted compounds by computing the standard deviation of a series of
injections of the lowest possible standard in synthetic urine and multiplying the standard deviation
by ten. The matrix matched recoveries ranged from 55%-105% with less than 10% of relative
standard deviation (RSD) for all compounds. Method accuracy, based on the nominal values of
the QC samples, ranged between 75%-125%. The coefficient of correlation of each calibration
curve was greater than or equal to 0.99 for all compounds, with a linear range from 1 or 2 ng/L to
200 ng/L (compound specific). These method performance characteristics indicate that the
method provides sufficient reliability for use in the analysis of perfluorinated alkyl compounds in
human urine.
P-12 Method Development for the Analysis of PFOA in Gestationally Exposed Mice —
Serum, Urine, Amniotic Fluid, and Whole Pups
Jessica L. Reiner, Mark J. Strynar, Shoji F. Nakayama, Amy D. Delinsky, Jason P. Stanko,
Suzanne E. Fenton, and Andrew B. Lindstrom
NERL and NHEERL, ORD, USEPA, Research Triangle Park, NC
Perfluoroalkyl acids (PFAAs) have received growing attention because of their widespread
environmental and biological presence. One PFAA, perfluorooctanoic acid (PFOA), has been
subject to increased scrutiny because of its detection in human blood samples from around the
world. Recent studies with mice have shown that dosing pregnant dams with PFOA during
gestation gives rise to a dose -dependent mortality in the litters, reduction in neonatal body weight
for the surviving pups, and subsequent deficits in mammary gland development in comparison to
controls. The actual body burdens of PFOA in dams and pups that are associated with these
endpoints have not been determined, in part due to lack of robust analytical methods for these
matrices. Such information would be very helpful in reducing the uncertainties of the risk
assessment process. In order to do a more thorough evaluation of the pharmacokinetics in utero,
pregnant CD-1 mice were dosed with PFOA at concentrations of 0.1 mg/kg, 1.0 mg/kg, and 5.0
mg/kg body weight on gestation day 17, with dam and pup serum, urine, amniotic fluid, and whole
mouse pups being isolated for method development and analysis. The analytical methods and
performance data are presented here. Preparation of mouse serum and amniotic fluid involved
DEQ-CFW 00000897

the addition of formic acid, followed by the addition of acetonitrile to precipitate proteins. Mrnise.
urine was diluted with formic acid and extracted using solid -phase extraction (SPE) with WatersT""
weak anion exchange (WAX) cartridges. For whole pup samples, the weighed pups were
homogenized and digested with 0.01 M NaOH in methanol. Cleanup was preformed by SPE with
WAX cartridges using methods previously established for other biological matrices. Extracted
samples were analyzed using Waters AcquityTM Ultra Performance LC interfaced with a Waters
Quattro Premier XE triple quadrupole mass spectrometer (UPLC-MS/MS). The resulting methods
provide excellent accuracy (100 ± 10%) and reproducibility (coefficient of variance between 2 and
15%) and will be used for future measurements. Tissue specific measurements of PFOA in serum,
urine, amniotic fluid, and whole pup homogenate will be used to more completely describe the
dose -response relationships for the most sensitive health outcomes and inform pharmacokinetic
models that are being developed and evaluated.
P-13 Interrogating the Interactions of Perfluorinated Carboxylic Acids in Human Blood
Using Nuclear Magnetic Resonance (NMR) Spectroscopy
Jessica C. D'eon, Andrew Baer, Rajeev Kumar, Andre Simpson and Scott Mabury.
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON CA
Unlike traditional organic pollutants that accumulate in lipid -rich adipose tissue, perfluorinated
sulfonic acids (PFSAs) and perfluorinated carboxylic acids (PFCAs) accumulate in proteineous
tIS$I,1P$ Rl lr.h aR thp- hlnnrl lixrer and kirinPy c• 1-h imnn PPr A rnntnminatinn is relevant as
•�•-� �•••� ••M• ...V14ull lulu 41V 11 IV relevant lAJ
perfluorooctanoic acid (PFOA) is detected in sera from the North American population at about 5
ng/mL (1). At concentrations of about 40 mM, serum albumin is the most prevalent protein in
blood and the most likely site for PFCA interactions in blood. Previous studies have characterized
interactions between PFSAs and PFCAs with serum albumin using mass spectrometry and
binding assays (2, 3). In this study we wanted to expand upon this understanding using nuclear
magnetic resonance (NMR) spectroscopy to observe the interaction PFCAs in human sera
without isolation or prior treatment of the sample. We used saturation transfer difference NMR
(STD-NMR) to determine the major site of interaction for perfluorohexanoic acid (PFHxA) and
perfluorooctanoic acid (PFOA) in human sera. This technique works by irradiating a component of
the mixture, this component then becomes saturated and transfers some of this energy to species
in close contact, which are subsequently detected. Using STD-NMR we were able to identify
serum albumin as the major site of interaction for PFHxA and PFOA in human sera. We were
also able to identify the orientation of PFHxA and PFOA in the serum albumin binding sites. Both
PFCAs were positioned with their fluorinated tails in the binding site and their carboxylate heads
pointed towards the surface. This position suggests that PFCAs are interacting with the fatty acid
binding sites on serum albumin, which x-ray crystallography has shown contain hydrophobic
pockets with cationic surface sites (4). The interactions described here may help understand the
pharmacokinetics of PFCA accumulation in human sera.
(1) Calafat, A. M.; Kuklenyik, Z.; Caudill, S. P.; Reidy, J. A.; Needham, L. L. Perfluorochemicals in
pooled serum samples from United States residents in 2001 and 2002. Environ. Sci. Technol.
2006, 40, 2128-2134.
(2) Jones, J. D.; Hu, W.; De Coen, W.; Newsted, J. L.; Giesy, J. P. Binding of perfluorinated fatty
acids to serum proteins. Evnviron. Toxicol. Chem. 2003, 22, 26392649.
(3) Han, X.; Snow, T. A.; Kemper, R. A.; Jepson, G. W. Binding of perfluorooctanoic acid to rat
and human plasma proteins. Chem. Res. Toxicol. 2003 16 775-781.
(4) Bhattacharya, A. A.; Grune, T.; Curry, S. Crystallographic analysis reveals common modes of
binding of medium and long -chain fatty acids to human serum albumin. J. Mol. Biol. 2003, 303,
721-732.
DEQ-CFW 00000898

P-14 Bioaccumulation and Biortransformation of 8:2 FTOH Acrylate
Craig M. Butt', Derek C.G. Muir2, Scott A. Mabury'
'Department of Chemistry, University of Toronto
2Water Science & Technology Directorate, Environment Canada
In recent years perfluorinated carboxylates (PFCAs) and sulfonates (PFSAs) have received a
great deal of scientific and regulatory attention. This is due, in part, to their apparently ubiquitous
global presence in wildlife, including those from remote regions. However, the source of PFCAs
and PFSAs is not fully understood. Recent studies have shown that precursor compounds can
be biotransformed by rats and microbes to yield PFCAs and PFSAs. One potential precursor is
the 8:2 fluorotelomer acrylate (8:2 FTOH acrylate), a common monomer used in fluorotelomer
based polymers. Fluorotelomer based polymers are incorporated into many commercial products
for their hydrophobic and lipophobic properties. The present study investigated whether the 8:2
FTOH acrylate could be bioaccumulated and subsequently biotransformed to PFCAs by rainbow
trout. Juvenile rainbow trout were purchased from a local hatchery and exposed to the 8:2 FTOH
acrylate via commercial fish food dosed at a concentration of 93 µg/g. Fish were fed the dosed
food during the five day uptake phase and fed clean food during the 8 day depuration phase.
Tissues were analyzed for the parent compound as well as suspected metabolites. The
intermediate metabolites, 8:2 saturated and unsaturated telomer acids (8:2 FTCA & 8:2 FTUCA)
and 7:3 FTCA, were observed within 1hr of dosing. Perfluorooctanoate (PFOA), the terminal
metabolite was observed with 4hrs of dosing. These results indicate that 8:2 FTOH acrylate was
rapidly taken up and biotransformed by the fish. In an additional experiment, fish were dosed
with the intermediate metabolites, separately, in order to elucidate the metabolism mechanism.
P-15 Biodegradation of Polyfluoroalkyl Phosphate Surfactants as a Source of
Perfluorinated Carboxylic Acids and Fluorotelomer Acids
Holly Lee, Jessica D'eon, Scott A. Mabury
Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6
The widespread occurrence of perfluorinated carboxylic acids (PFCAs) has raised public
awareness due to their bioaccumulative properties, potential toxicity in humans and animals, and
environmental persistence. In addition to production plants as direct sources, an alternative route
of exposure is the release of PFCA precursors, such as fluorotelomer alcohols (FTOHs), that are
either present as residuals or as degradation products from the breakdown of fluorotelomer-
based products. One example of these fluorotelomer-based compounds is the polyfluoroalkyl
phosphate surfactant (PAPS)', commonly used as grease resistants in food packaging paper and
as anti -foaming additives in pesticides. Concern for these compounds as potential PFCA sources
via degradation is implied in the recent U.S. EPA revocation of the tolerance for perfluoroalkyl
phosphates as inert ingredients in pesticide formulations in 2006.2 To date, knowledge of PAPS
degradation is limited to one study where rat metabolism of the 8:2 FTOH mono- and diPAPs
showed that their phosphate ester linkages are biologically labile and hence, both congeners may
be biotransformed into 8:2 FTOH, and ultimately, to PFCAs and other FTOH metabolites .3 What
has not yet been fully explored is the potential for PAPS to be microbially degraded and the
current investigation demonstrated the biodegradation of 8:2 monoPAPS using activated sewage
sludge from a local wastewater treatment facility. A purge -and -trap system coupled to gas
chromatography -mass spectrometry was employed to monitor the production of 8:2 FTOH which
leveled off at day 44, resulting in 19% transformation of 8:2 monoPAPS in the 72-day experiment.
The effect of the length of the singly -chained monoPAPS on the lability of the ester linkage was
also probed in which 4:2, 6:2, 8:2, and 10:2 monoPAPS were simultaneously subjected to
microbial hydrolysis as in the previous experiment. Results showed that the 4:2 congener was
produced the fastest and at the highest level, followed by 6:2 FTOH, then 8:2 FTOH, and finally
10:2 FTOH, suggesting that the microbial cleavage of the P-O bond in monoPAPS was sterically
controlled by chain length. As FTOH has been shown to be a prevalent source of PFCAs, the
DEQ-CFW 00000899

biodegradability of PAPS to FTOH shown here confirms the compound as a likely contributor to
the load of PFCAs in the environment.
1. General structure of PAPS: (RfCH2CH2O),P(0)(OH)y where Rf is a perfluorinated chain
containing 1-10 carbons; x = 1 or 2; y = 1 or 2; and x + y = 3
2. U.S. EPA. Mono- and bis-(1 H, 1 H, 2H, 2H-perfluoroalkyl) phosphates where the alkyl
group is even numbered and in the C6-C12 range; Proposed Revocation of Pesticide
Inert Ingredient Tolerance Exemption; U.S. EPA public Docket OPP-2006-0253;
Washington, DC, 2006.
3. D'eon, J.; Mabury, S.A. Production of perfluorinated carboxylic acids (PFCAs) from the
biotransformation of polyfluoroalkyl surfactants (PAPS): Exploring routes of human
contamination. Environ. Sci. Technol. 2007, 41, 4799-4805.
4. Dinglasan, M.J.A.; Ye, Y.; Edwards, E.A.; Mabury, S.A. Fluorotelomer alcohol
biodegradation yields poly- and perfluorinated acids. Environ. Sci.
P-16 Modeling Single and Repeated Dose Pharmacokinetics of PFOA in Mice
John F. Wambygh , Inchio L u , Christopher Laut, Roger G. Hansom, Andrew B. Lindstrom§,
Mark J. Strynar, , R. Dan Zehr , R. Woodrow Setzerh, and Hugh A. Barton
National Center for Computational Toxicology, (Reproductive Toxicology Division, National
Health and Environmental Effects Research Laboratory, and Human Exposure and
Atmospheric Science Division, National Exposure Research Laboratory, Office of Research and
Development, U.S. Environmental Protection Agency, Research triangle Park, North Carolina
27711
Perfluorooctanoic acid (PFOA) displays complicated pharmacokinetics in that plasma serum
concentration indicates a long half life — 3.8 years in humans (Olsen et al. 2007) — but also rapidly
achieves steady-state (Lau et al., 2006). Attempts to address this have included using different
pharmacokinetic parameters for different doses (Washburn et al., 2005, Trudel et al., 2008) as
well as biologically -based models such as the saturable resorption model of Andersen et al.
(2006). We examined plasma concentration time -courses for female CD1 mice after single, oral
doses of 1, 10, and 60 mg/kg of PFOA. We found that the pharmacokinetics for the two lower
doses are well -described by an empirical, one -compartment model. The predictions for that
model are not, however, consistent with the 60 mg/kg data which was instead found to be
consistent with a two -compartment model that was in turn inconsistent with the two lower doses.
We then examined plasma concentrations observed after 7 and 17 daily doses of 20 mg/kg
PFOA from Lau et al. (2006) as well as additional 17-day studies. The 1 and 10 mg/kg one -
compartment fit was not consistent with repeated dose concentrations while the 60 mg/kg two -
compartment was. We found that some level of consistency between low and high doses could
be achieved using the saturable resorption model of Andersen et al. (2006) in which PFOA is
cleared from the plasma into a filtrate compartment from which it is either excreted or resorbed
into the plasma by a process with a Michaelis-Menten form. A maximum likelihood estimate
found a transport maximum of Tm = 860.9 (1298.3) mg/L/h and half -maximum concentration of KT
= 0.0015 (0.0022) mg/L where the estimated standard errors (in parentheses) indicated large
uncertainty. The estimated rate of flow into and out of the filtrate compartment, 0.6830 (1.0131)
L/h was too large to be consistent with a biological interpretation of the filtrate. For these model
parameters we estimated that a single dose greater than 40 mg/kg, or a daily dose in excess of 5
mg/kg were necessary to observe non -linear pharmacokinetics for PFOA in female CD1 mice.
This work was reviewed by EPA and approved for publication but does not necessarily reflect
official Agency policy.
DEQ-CFW 00000900

P-17 Modeling the Pharmacokinetics of Perfluorooctanoic Acid During Gestation and
Lactation in Mice
Chester E. Rodriguez and Hugh A. Barton
National Center for Computational Toxicology, US EPA, RTP, NC, USA.
Perfluorooctanoic acid (PFOA) is used as a processing aid for the production of commercially
valuable fluoropolymers and fluoroelastomers. It has been widely detected in biological
organisms including humans whose estimated blood levels are in the low ppb levels for the
general US population. PFOA is metabolically stable and exhibits a plasma half-life of 3-5 years
in humans. In mice, PFOA induces developmental toxicity in the form of full litter resorption,
compromised postnatal survival, delayed growth and development, and altered pubertal
maturation. While some postnatally observed developmental effects have been attributed to
gestational exposure, it remains to be elucidated whether these result from a higher internal dose
(pharmacokinetics) and/or exposure during a developmentally sensitive period
(pharmacodynamics). To address the pharmacokinetics of PFOA during gestation and lactation, a
biologically -supported dynamic model was developed. A two compartment system linked via
placental blood flow described gestation, while milk production linked the dam to a pup litter
compartment during lactation. Mathematical functions described the growth of the dam,
conceptus, placental blood flow, and nursing pups. Serum:fetal and serum:milk partition
coefficients and milk production were estimated from published literature. Absorption and
elimination were described as 1st order processes. The model reasonably simulated reported
serum levels in non -lactating and lactating dams as well as nursing pups. Lactation is predicted to
be an important clearance pathway for the dam and correspondingly a major source of exposure
for the nursing pups. However, developmentally sensitive periods may render gestation more
important toxicologically. The incorporation of renal resorption was necessary to simulate the
non -linear behavior of serum levels in the adult non -pregnant mouse, especially at doses >
1 mg/kg/day at which full -litter resorption occurs in the pregnant mouse.
These analyses indicate that a linear pharmacokinetic model may be appropriate in the analysis
of gestational and lactational exposures to doses of PFOA _< 1 mg/kg/day, though this may be
dependent on strain and toxicological endpoint.
These modeling efforts provide an initial template for further explorations of the pharmacokinetics
of PFOA relevant to one -generation toxicity studies.
(This work does not reflect official Agency policy).
P-18 8-2 Fluorotelomer Alcohol: Liver Glutathione Status, Metabolite Kinetics in
Tissues, and Excretion and Metabolism with Daily Oral Dosing
W.J. Fasano, M.P. Mawn , D.L. Nabb, X. Han, B. Szostek and R. C. Buck.
E.I. DuPont de Nemours & Co., Inc., Wilmington, DE.
Male and female rats were administered 8-2 Fluorotelomer Alcohol (8-2 FTOH) by oral gavage for
45 days and livers collected periodically to evaluate glutathione status, and samples of liver,
kidney, fat, thyroid, bone marrow, thymus, skin and plasma were analyzed for 8-2 FTOH and
14
perfluorinated metabolites. On day 46, conditioned and naive rats were administered [ C]8-2
FTOH and sacrificed 1-2 hours post dose to determine the percent of covalently bound
14
radioactivity in liver, kidney and plasma. Also, conditioned rats were administered [ C]8-2 FTOH,
maintained for 7 days, sacrificed and a complete material balance performed along with
metabolite identification in excreta and tissues. Lastly, selected tissues and excreta were
processed with DNPH and screened by LC/MS for aldehyde and ketone metabolites. Overall,
liver glutathione was unaffected by daily oral 8-2 FTOH administration. The most ubiquitous
metabolites in tissues were 7-3 Acid and PFO; 8-2 FTOH had the greatest concentration in fat
and most metabolites exhibited steady-state concentration by day 25. There were no differences
in the percent of covalently bound radioactivity in naive and conditioned rats. Following a single
DEQ-CFW 00000901

14
oral dose of [ C]8-2 FTOI I, >74% was eliminated in the feces, which contained primarily 8-2
FTOH. Urine was a minor elimination pathway and contained PFO, 7-2 secondary FTOH-
glucuronide and 8-2 unsaturated FTOH N-acetyl cysteine (females only). The greatest
percentage of the administered dose was found in the liver, fat and skin; in liver, the principle
metabolites were PFO, PFN, 8-2 FTOH-sulfate and 7-3 Acid (males only). In the kidney, PFO
(males only) and 8-2 FTOH-sulfate (females only) was observed, and in plasma, 7-3 Acid, PFO
and 8-2 FTOH-sulfate (females only) was detected. DNPH-derivatized tissues/excreta confirmed
the presence of 7-2 Ketone, 7-3 aldehyde and 7-3 unsaturated aldehyde. These results provide a
comprehensive evaluation of 8-2 FTOH pharmacokinetics and metabolism following sub -chronic
exposure in the rat.
P-19 Comparative in silico modeling of environmental and therapeutic classes of
Perfluorinated Chemicals (PFCs): ADME properties, virtual receptor profiling and
generalized PBPK models
Michael -Rock Goldsmith', Rogelio Tornero-Velezl, Thomas R. Transue3, Stephen B. Little'`,
James R. Rabinowitz2, Curtis C. Daryl
' National Exposure Research Laboratory, U.S. EPA. Research Triangle Park, NC, USA
2 National Center for Computational Toxicology, U.S. EPA, RTP, NC;
3 Lockheed -Martin Information Technology, RTP, NC;
Perfluorinated chemicals (PFC) have unique physicochemical/biological properties that have
historically made them amenable to numerous industrial and biomedical applications. Therapeutic
class PFCs used in prosthetics, contrasting agents, artificial blood replacements and partial liquid
ventilation have low toxicity (NOEL > g/kg), resist metabolic degradation and form stable micelles
that remain intact in vivo with short serum half-lives. Furthermore, the pharmacokinetic behavior,
elimination routes, and benign histopathology of various tissues exposed to these chemicals are
well documented. On the other hand, the environmentally persistent PFCs that are by-products of
perfluorotelomer industries have significantly higher potencies (i.e., NOEL < mg/kg) longer serum
half-life, and have been implicated with multiple adverse effects endpoints with attributable risk
down to the molecular level. Yet, despite the multitude of in vivo and in vitro studies revolving
primarily around PFOA/PFOS (C8/C7), much remains to be learned from studying congeneric
PFAAs so that the biological disposition and effects may be extrapolated on a molecular
structural level: In silico methods are ideal candidates to explore receptor binding, PBPK and
ADME property relationships on such a basis.
Using both established 2D-physicochemical descriptors in addition to predicted ADME properties
generated by 3D-QSAR models in Epiwin (US -EPA) and QikProp (Schrodinger Inc.) respectively,
we built generalized PBPK models (Cahill et al Env Tox & Chem, 22(1): 26-34) to compare and
contrast the differences in biological disposition and elimination profiles of "environmental" (-20
chemicals) and "therapeutic" (14 chemicals) classes of PFCs on the basis of molecular structure.
In addition we performed multiple -target molecular docking profiles using eHiTS (Simbiosys Inc.)
whereby the 3D structure of the PFCs and an additional 135 PPAR-UF_1 high affinity ligands from
kibank (http://kibank.iis.u-tokyo.ac.]p/ ) were independently docked into 151 unique biological
targets (comprised of nuclear receptors, oxidoreductases, kinases, phosphatases, lipid carrier
proteins and serum proteins). Docking provides 3D coordinates of the ligand molecules bound to
a given receptor and the. scores are surrogates for the magnitude of their mutual interaction. The
multiple -target scores were subsequently analyzed using (1) PCA and (2) hierarchical cluster
analysis in Partek. In addition chemical -receptor linkage maps were generated in CytoScape.
These analyses have provided additional insight on target selectivity and specificity (a) in
comparison to other known chemicals (b) as a function of chain length and (c) as a result of
structural features,
Both the data and analyses provide alternative (in silica) apprnaches to deal with multi-
dimensional data on a comparative basis and how in turn such studies may be used in rapid and
rational hypothesis generation, development of new structure -activity relationships and discovery
DEQ-CFW 00000902

toxicology in general for PFCs.[This work was reviewed by EPA and approved for publication but
does not necessarily reflect official Agency policy.]
P-20 Consequences of Prenatal PFOA Exposure on Mouse Mammary Gland Growth and
Development in F1 and F2 Offspring
White, Sally S.'; Hines, Erin P.2; Stanko, Jason P.2; Fenton, Suzanne E.2
' UNC, Curriculum in Toxicology, Chapel Hill, NC, 2US EPA, ORD, NHEERL, RTD, RTP, NC,.
Perfluorooctanoic acid (PFOA) is a known developmental toxicant with ubiquitous presence in
industrial applications and the ambient environment. We previously reported that prenatal PFOA
exposure results in delayed development of the mouse mammary gland (MG) in F1 female
offspring. To determine consequences of this delayed MG development on lactational function
and subsequent development of F2 offspring, F1 females exposed transplacentally to 0, 1 or 5
mg PFOA/kg/day (control, 1P, 5P; gestation days 1-17), were bred to generate F2 offspring (no
direct exposure to PFOA). F2 offspring were monitored for growth and development from
postnatal day (PND) 1-22, and F1 dam MG function was assessed on PND10 by lactational
challenge. MG tissue was isolated from both F1 and F2 females at necropsy on PND10 and 22,
and scored for age -appropriate development on a 1-4 scale. As hypothesized, MG morphological
scores were lower (p<0.05) in 1 P and 5P F1 dams evaluated on PND10, and in 5P F1 dams on
PND22. However, no effect of treatment on milk production (volume after 30-min nursing) or
maternal behavior (time to initiate nursing) was detected on PND10. Body weight of F2 pups was
similar between groups on PND1-10, however, starting on PND14 and persisting through PND22
body weight of 1 P F2 offspring was significantly higher than controls. MG developmental scores
in F2 pups were similar to control at PND10, but lower among P5 F2 offspring on PND22. The
time of eye-opening was similar in all groups. These findings confirm previous PFOA-induced
delays in lactating mammary gland differentiation, with a current LOEL for these effects at 1
mg/kg/d, and suggest that these delays have little, if any, deleterious effects on the F2 offspring
early in life; further evaluation of F2 offspring will illuminate whether adverse health effects may
result in adult life. (This abstract does not necessarily reflect EPA policy; SSW funded by EPA
CR833237, NIH T32 ES007126.)
P-21 Differential Effect of Peripubertal Exposure to Perfluorooctanoic Acid on Mammary
Gland Development in C57B1/6 and Balb/c Mouse Strains
Ying Tan' 2, Chengfeng Yang''2'4, Jack Harkema3 and Sandra Z. Haslam''2
Department of Physiology', Breast Cancer and the Environment Research Center 2, National
Center for Food Safety and Toxicology 3, Center for Integrative Toxicology 4, Michigan State
University, East Lansing, MI 48824
Perfluorooctanoic acid (PFOA) is a chemical widely used in the production of fluoropolymers for
making numerous industrial and consumer products. PFOA is one of the most common persistent
organic pollutants in environment, and its presence in humans and wildlife has raised
considerable health concerns. Toxicological studies have found that PFOA is an agonist for
peroxisorrme pro!iferator-activated receptor (PPAR) and causes Leydig cell adenomas, mammary
fibroadenomas and liver cancer in rats. While exposure to PFOA throughout gestation induces
general developmental toxicity in rats and mice, offspring of mice exposed during gestation to low
dose PFOA display a defect in mammary gland development resulting in stunted mammary
ductal growth and branching at postnatal day 10 and 20. The peripubertal period is an important
window of susceptibility to environmental exposures that may predispose humans to increased
breast cancer risk later in life. Nothing is known about the effect of peripubertal PFOA exposure
on mammary gland development. Thus, our current studies have examined PFOA-induced
effects on pubertal mouse mammary gland development in Balb/c and C57131/6 mice. We found
that the effects of PFOA exposure differed significantly between the two mouse strains.
DEQ-CFW 00000903

Three-week old female Balb/c and C57BI/6 mice were given PFOA by oral gavage 5 times per
week for 4 weeks. The dosages were 0 (vehicle control), 1, 5, or 10 mg PFOA/kg BW. Mammary
glands, livers and uteri were collected for histological examination. A significant decrease in BW
was observed only at 10 mg/kg dose. Dose dependent increases of relative liver weight were
detected in both strains of mice and increased to a greater extent in C57BI/6 mice. Liver
histopathology revealed that the principal morphologic alteration in the livers of both strains of
mice was a dose -dependent hepatocellular hypertrophy. However, at each dose the extent and
severity of the lesions were greater in C57131/6 mice. PFOA treatment caused a significant and
dose -dependent decrease of relative uterine weight in Balb/c mice. In contrast, the 1 mg/kg
PFOA dose significantly increased the relative uterine weight in the C5713I/6 mouse strain
whereas the 10 mg/kg PFOA dose caused a significant decrease in relative uterine weight. PFOA
treatment inhibited mammary gland growth in a dose dependent manner, as evidenced by
reduced duct length and decreased numbers of end buds, in the Balb/c strain. However, in
striking contrast, PFOA treatment in the C57131/6 strain resulted in a significant increase in end
bud number, generalized mammary gland stimulation and no inhibition of ductal growth. This
effect was maximal at the 5 mg/kg dose. An inhibitory effect on mammary gland development
was seen at the 10 mg/kg dose. A dose dependent effect causing delayed vaginal opening was
also observed in both strains.
In summary, pubertal PFOA exposure causes hepatocellular hypertrophy and delayed vaginal
opening in both mouse strains. However, the effects of PFOA on the uterus and mammary gland
were significantly different between the two mouse strains. In the Balb/c mice there was a dose
dependent inhibitory effect whereas in the (57R1/6 strain there was a stimi ilatnry eff-rt nn the
mammary gland and uterus at low doses and an inhibitory effect of a high dose. The molecular
basis for the differential responses of two mouse strains to pubertal PFOA exposure is not known.
Whether PFOA affects mouse mammary gland development through a direct or indirect
mechanism remains to be determined. Importantly, the finding of the striking differences in the
effect of pubertal PFOA exposure on mammary gland and uterus in two genetic backgrounds in
the same species suggest that caution should be used when drawing conclusions about the
effects of PFOA on a given target tissue on the basis of studies in a single mouse strain. (This
study was supported by the Breast Cancer and the Environment Research Center Grant 1-UO1
ESO12800 01 from National Institute of Environmental Health Sciences).
P-22 Prenatal Exposure to Perfluorooctane Sulfonate or Perfluorononanoic Acid
Increases Blood Pressure in Adult Sprague Dawley Rat Offspring
Ellis -Hutchings RG, Zucker R, Lau C, Grey BE, Norwood J, Jr. and Rogers JM.
Reproductive Toxicology Division, NHEERL, ORD, US EPA, Research Triangle Park, NC
The long term health effects of exposure to environmental chemicals during pregnancy have
been identified as a significant data gap by several reproductive and developmental toxicology
working groups over the past decade. In response, we have established a program to investigate
the long-term adult health effects of adverse intrauterine environments induced by environmental
chemical exposure. We have incorporated perfluorooctane sulfonate (PFOS) and
perfluorononanoic acid (PFNA) as chemicals in this program due to their considerable interest to
the U.S. EPA and/or their well defined toxicological effects following developmental exposures.
Through the program's broad investigation into adverse adult health effects following prenatal
exposures to environmental chemicals, an increase in systolic blood pressure has emerged as a
consistent response with the majority of test chemicals. In this pester we will present Systolic
blood pressure findings in offspring of pregnant rats exposed to PFOS or PFNA, and
investigations into potential modes of action.
Timed -pregnant Sprague Dawley rats were treated by oral gavage with either PFOS (18.75
mg/kg in 0.5% Tween-20, gestation day (GD) 2-6) or PFNA (5 mg/kg in water, GD 1-20).
Exposure concentration, duration and gestational periods were selected based upon previous
research demonstrating either some maternal toxicity and/or a decrease in offspring birth weight.
DEQ-CFW 00000904

Corresponding vehicle and Dexamethasone (Dex) (subcutaneous injection of 0.6 mg/kg in water,
GD 16-20) exposures were included as negative and positive controls, respectively. At birth,
PFOS, PFNA and Dex treated pups were fostered to untreated control dams, while pups from
vehicle -treated control dams were cross -fostered within this group. Systolic blood pressure was
measured at several timepoints between 7-54 weeks of age using non-invasive tail cuff
photoplethysmography.
Exposure to either of the perfluouroalkyl acids or Dex caused a reduction in maternal body weight
gain during their respective exposure periods. A reduction in birth weight was evident in all
treatment groups, reaching statistical significance in offspring of PFNA- and Dex-exposed dams.
Catchup growth occurred and by weaning on postnatal day 21, no differences in body weight
were apparent among the groups. Systolic blood pressure was elevated by 10-15 mmHg as early
as 7-10 weeks of age in male offspring in all treatment groups when compared to the negative
controls. Female offspring in the PFNA group demonstrated elevations in systolic blood pressure
as early as 10 weeks of age, while PFOS and Dex female offspring showed an increase at 37
weeks of age, the next testing period. These results suggest that programming of systolic blood
pressure in juvenile and adult rats can be altered by prenatal exposure to PFOS or PFNA. We
are currently completing evaluations of key pathways involved in blood pressure regulation and
programming, including glucocorticoid and renin-angiotensin-aldosterone system components
and kidney nephron endowment. This abstract does not reflect EPA policy.
P-23 Adult Outcomes of Gestational or Adult Exposure to Perfluorooctanic Acid (PFOA)
in Female CD-1 Mice
Erin P. Hines', Sally S. White2, Jason P. Stanko', and Suzanne E. Fenton'
'US EPA, ORD, NHEERL, RTD, RTP, NC, 2 UNC, Curriculum in Toxicology, Chapel Hill, NC.
PFOA, an environmentally persistent chemical detected in humans and wildlife, is a surfactant
with wide consumer and industrial applications. Developmental exposure to PFOA is associated
with decreased body weight in neonates as well as other later life effects. This study addresses
whether prenatal exposure to PFOA also leads to adult weight gain and changes in organ weights.
Timed pregnant CD-1 mice (n>30 per dose group) were exposed to PFOA (0.01, 0.1, 0.3, and 1
or 5 mg/kg/day) via oral gavage over days 1 to 17 of pregnancy. At post -natal day 1 (PND1),
litter weights were recorded and the 5 mg/kg litters weighed significantly less than control animals.
At 18 months, the animals were sacrificed and body weight, organ weight, and fat weights
recorded. There was a significant increase in both body weight (0.01, 0.1, and 1 mg/kg) at 20-29
weeks and intrasubscapular brown fat in the 1 and 3 mg/kg PFOA group at 18 months when
compared to control animals. Liver, spleen, abdominal white fat and liver to body weight ratio
were not significantly different in any of the treatment groups. A subset of the gestationally
exposed females ovariectomized (ovx) at PND21 were followed concomitantly with the intact
animals. The body weights of these ovx animals showed no significant difference versus intact
animals when compared within dose groups. A final group of age -matched females were dosed
as adults (0, 1, 5 mg/kg PFOA) for 17 days and followed out to 18 months. These adult exposed
animals showed no significant increase in body weight and no significant changes in organ or fat
weight at 18 months when compared to controls. These data show a critical window of exposure
to PFOA leads to increased weight gain as an adult. Whether increased body weight associated
with prenatal PFOA exposure is associated with other health effects later in life is under
investigation. (This abstract does not necessarily reflect EPA policy.)
DEQ-CFW 00000905

P-24 Sodium Perfiuorohexanoate: Oral Repeated Dose Subchronic, One -Generation
Reproduction, Genotoxicity and Developmental Toxicology
B.P. Slezak, T.L. Serex, S.E. Loveless, R.C. Buck, S.H. Korzeniowski
E.I. DuPont de Nemours & Co., Inc., Wilmington, DE.
Sodium perfluorohexanoate (PFHxNa) was evaluated in subchronic, one -generation
reproduction, genotoxicity, and developmental toxicity studies. In the subchronic/one-generation
reproduction study, four groups of young adult male and female Crl:CD(SD) rats were
administered PFHxNa daily by gavage at dosages of 0, 20, 100, or 500 mg/kg/day. Rats were
dosed for 90 days and evaluated after one- and three- month recovery periods. In the
developmental study, time -mated female rats were dosed via gavage on GD 6-20 with the same
doses of PFHxNa used in the subchronic study. On GD-21 rats were euthanized and fetuses
were examined for soft tissue and skeletal alterations. The NOAEL for subchronic toxicity was 20
mg/kg/day, based on nasal lesions observed at 100 and 500 mg/kg/day. The relevance to
humans is unknown. The NOAEL for reproductive toxicity was 500 mg/kg/day, the highest dose
tested. No test substance -related effects were observed on reproductive parameters. The NOEL
for P 1 adult rats was 20 mg/kg/day (reduced body weight/gains in males at 100 mg/kg/day). The
NOEL for F 1 offspring was 100 mg/kg/day (reduced pup weights during lactation at 500
mg/kg/day). The NOEL for F1 adults was 100 mg/kg/day, (reduced body weight/gains in F1 males
and females and reduced food consumption in F i adult males at 500 mg/kg/day). Genotoxicity
studies of PFHxNa indicated no mutations in the bacterial reverse mutation assay or
chromosome aberrations in human lymphocytes. In the developmental study, there were no test
substance -related deaths or gross findings in the dams at any dose. The NOEL for the
developmental study was 100 mg/kg/day (maternal toxicity observed as decreased body weight
and food consumption and developmental toxicity based upon decreased fetal weights was
observed in rats administered 500 mg/kg/day). PFHxNa is therefore concluded not to present a
reproductive or developmental hazard. The lowest NOEL representing all of the studies
described above was 20 mg/kg/day.
P-25 Effects of Perfluorobutyrate on Thyroid Hormone Status in Rats
S. Chang', J. Bjork2, K. Wallace 2, and J. Butenhoffl
13M Company, St. Paul. MN; 2University of Minnesota, Duluth, MN
Perfluorobutyrate (PFBA) is a perfluorinated carboxylate that has been shown to be a peroxisome
proliferator activated receptor alpha (PPARa) agonist. Subchronic (28 d and 90 d) oral studies at
doses up to 150 mg/kg-d produced adaptive effects in male rats that included increased
hepatocellular hypertrophy and increased minimal -mild hypertrophy/hyperplasia of the thyroid
follicles. These effects were accompanied by hypothyroxinemia without elevation of thyrotropin
(TSH). We investigated the hypothesis that PFBA, like some other PPARa agonists, for example,
free fatty acids and aspirin, may compete for binding with thyroxine (T4), and increase peripheral
tissue turnover of T4.
Experiments evaluated: 1) potential for in vitro binding displacement of T4 by PFBA; 2) potential
in vivo binding displacement of T4 by PFBA (time -course and relation to serum PFBA
concentration); 3) disposition of 1251 from 1251-labelled T4 on dosing with PFBA in vivo; and 4)
expression of marker genes for thyroid hormone (TH) response in liver by quantitative RT-PCR.
Results demonstrated that: 1) PFBA does compete with T4 for binding in serum in vitro; 2) total
T4 was decreased, free T4 increased, and TSH decreased within 2 hours after a single dose of
PFBA, and homeostasis was regained within 72 hours corresponding to PFBA serum
concentration; 3) 1251 excretion in feces was increased by PFBA treatment; and 4) expression of
marker genes for TH response did not suggest hypothyroid status.
DEQ-CFW 00000906

Conclusion: PFBA increases thyroid hormone turnover and transiently increases free T4.
Therefore, PFBA, like some other PPARa agonists, may act as a thyroid -displacement compound.
P-26 Comparison of the Activities of Carboxylates and Sulfonates of Perfluoroalkyl
Acids (PFAA) of Various Carbon Chain Lengths on Mouse and Human Peroxisome
Proliferator-Activated Receptor -Alpha (PPARa) in COS-1 Cells
Wolf, Cynthia J., Takacs, Margy L., Schmid, Judith E., Lau, Christopher, Abbott, Barbara D.
RTD, NHEERL, ORD, US EPA, Research Triangle Park, NC, USA
PFAAs are used in consumer products and persist in the environment. They elicit adverse effects
on rodent development and neonatal survival, and may act via PPARa to produce some of their
effects. The induction of mouse and human PPARa activity by perfluorinated carboxylic acids
(PFCAs) and perfluorinated sulfonic acids (PFSAs) of various carbon chain lengths was tested
using a transiently transfected COS-1 cell assay. COS-1 cells were transfected with either a
mouse or human PPARa receptor luciferase reporter plasmid. After 24 hours, cells were exposed
to either vehicle control (DMSO [0.1 %]), PPARa agonist (WY14643, [10 pM]), PFAA vehicle
control (water or DMSO [0.1 %]); perfluorooctanoic acid (PFDA) or perfluorononanoic acid
(PFNA) at 0.5-100 pM; perfluorobutanoic acid (PFBA), perfluorodecanoic acid (PFDA), or
perfluorohexanoic acid (PFHxA) at 5-100 pM; perfluorohexane sulfonate (PFHxS) at 5-100 pM; or
perfluorobutane sulfonate (PFBS) or perfluorooctane sulfonate (PFOS) at 1-250 pM. After 24 hrs
of exposure, PPARa plasmid luciferase activity was measured. Lowest observed effects
concentration (LOEC) was determined by ANOVA (p< 0.05). Each of the PFAAs activated the
mouse and the human PPARa plasmid in a concentration dependent fashion, except PFDA,
which did not activate human PPARa plasmid at any concentration. Activation of both mouse
and human PPARa was positively correlated with carbon chain length, for PFBA (C4), PFHxA
(C6), and PFOA (C8). PFDA (C10) induced high activity in the mouse PPARa plasmid (LOEC, 5
pM). PFOA produced a biphasic dose -response with a plateau at high doses. PFSAs generally
induced lower activity of mouse and human PPARa compared to PFCAs. We have found that
PFCAs of different chain lengths induce activity of the mouse and human PPARa differently, and
that PFSAs are weaker activators of mouse and human PPARa than PFCAs. This abstract does
not necessarily reflect EPA policy.
P-27 Development of Health -based Drinking Water Guidance for PFOA
Gloria Post
New Jersey Department of Environmental Protection, Trenton, NJ.
Health -based drinking water guidance for perfluorooctanoic acid (PFDA) was developed in
response to a request from a public water supply in New Jersey with PFOA detections. The
starting point for the assessment was the USEPA Draft Risk Assessment of the Potential Human
Health Effects Associated with Exposure to Perfluorooctanoic Acid and Its Salts (2005) and the
USEPA Science Advisory Board (2006) review of this assessment. More recent studies which
were not included in the USEPA (2005) draft risk assessment, including studies of developmental
effects in mice, were not considered in developing the drinking water guidance. The USEPA draft
risk assessment (2005) aimed to evaluate the significance of the exposure of the general
population to PFDA and developed margins of exposure (MOEs) in humans compared to
LOAELs and NOAELs from animal studies. USEPA (2005) classified PFOA as a suggestive
carcinogen, while the SAB (2006) classified it as a likely carcinogen. Since the half-life of PFOA
in humans is much longer than in animals, MOEs are based on comparison of animal blood levels
and human blood levels rather than administered doses. However, USEPA did not address the
relationship between intake of PFOA and blood levels in humans, and this information is needed
to develop drinking water guidance. A study of an Ohio community ingesting water contaminated
with PFOA indicates that there is a 100-fold concentration factor between PFOA in drinking water
and blood (e.g., 1 ug/L in drinking water results in 100 ug/L in blood. Emmett et al., 2006), and
DEQ-CFW 00000907

this factor was used to develop health -based drinking water concentrations for the non -cancer
and cancer endpoints identified by USEPA (2005). Similar results were obtained by others using
the ratio of half-lives of PFOA in humans and experimental animals. The most sensitive
endpoints were decreased body weight and hematological effects in a chronic study in female
rats, and the guidance value based on this endpoint is 0.04 ug/L. The drinking water
concentration based on cancer at the one in one million risk level is 0.06 ug/L. This assessment is
available at http://www.nj.gov/dep/watersupply/pfoa dwquidance.pdf.
P-28 Derivation of Groundwater Standards for Perfluorobutyric Acid (PFBA)
and Perfluorooctanoic Acid (PFOA)
Goeden, Helen; Rita Messing; Pamela Shubat
Minnesota Department of Health, St. Paul, MN, USA
Perfluorochemicals (PFCs) have been found in the groundwater in Washington County,
Minnesota. The chemical structures of PFCs make them resistant to environmental degradation.
PFCs are very soluble in water but unlike most groundwater contaminants PFCs are slowly
removed from the body, with half-life estimates for some PFCs of nearly 9 years. In contrast, the
half-life in some laboratory animals is a few hours to a few weeks.
PFCs present unique challenges for risk characterization. The Minnesota Department of Health
(MDH) has incorporated new risk characterization approaches to derive health based criteria for
PFCs.
MDH evaluates the health risks of contaminated groundwater and establishes human health
based values, expressed as micrograms of contaminant per liter of groundwater (pg/L), that
represent a level that is without appreciable risk to human health. Historically, noncancer health
based values were based on protecting against adverse health effects from long-term exposure
and combined an adult intake rate with a chronic reference dose.
However, recent legislative mandates have placed an increasing emphasis on protecting children
from environmental exposures due to greater exposure (on a per body weight basis) and
mounting scientific evidence to support the vulnerability of the developing fetus and child.
MDH has responded by incorporating a variety of risk characterization approaches recommended
by recent US EPA guidance into the process utilized to derive health based criteria. The
derivation process includes: 1) assessing evidence of life stage sensitivity; 2) assessing the
relationship between the effects observed and duration of exposure; 3) selecting endpoints based
on characterization of the entire database rather than the "critical' study; 4) incorporating water
intake rates based on age and duration considerations; and 5) comparing the calculated HRL
values for different durations to ensure that the final values are protective of human health.
The revised derivation process was used to derive health based criteria for perfluorobutyric acid
(PFBA) and perfluorooctanoic acid (PFOA). The derivation process demonstrated that the historic
reliance on chronic assessments may not be protective of less -than -chronic exposures. A major
challenge encountered in the derivation process involved interspecies extrapolation toxicokinetic
issues such as differences in internal dose (serum levels) and estimation of internal dose levels
from short duration exposure as well as toxicodynamic issues such as human sensitivity to
adverse effects.
A limited number of toxicokinetic and toxicity studies have been conducted on PFBA. The half-
life of PFBA in humans has been estimated to be only a few days. Based on this limited data set
RfDs for acute, short-term, subchronic and chronic exposure were derived. A corresponding time -
weighted water intake rate was estimated for each duration. The resulting calculated health
based values were 8, 7, 8 and 10 ug/L for acute, short-term, subchronic and chronic. Longer
duration values must be protective of the periods of higher exposure which occur within the
longer duration period. I heretore, the tinal subchronic and chronic health based values were set
at the short-term value of 7 ug/L.
DEQ-CFW 00000908

Unlike PFBA, the half-life of PFOA in humans is nearly 4 years. The toxicokinetic information
necessary to confidently estimate acute, short-term or subchronic RfDs for PFOA which slowly
accumulates over time is currently not available. Additional uncertainties include: toxicokinetics in
young infants (the most highly exposed population via water ingestion) and pre-existing body
burden at birth (PFOA readily crosses the placenta). As a result health based criteria were not
derived for acute, short-term or subchronic exposure durations. A human equivalent dose
associated with a steady-state serum level was used to derive a chronic health based value of 0.3
ug/L.
DEQ-CFW 00000909

U.S. Environmental Protection Agency
PFAA Days II Workshop
.Dune 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
Barbara Abbott
Robert Bilott
Antonia Calafat
Principal Investigator
Partner
Lead Research Chemist
US EPA
Taft Stettinius & Hollister LLP
CDC
Reproductive Toxicology Division
d25 Walnut Street, Suite 1800
4770 Buford Hwy, MS F-53
(MD67)
Cincinnati, OH 45202
Atlanta, GA 30345
NHEERL/ORD
Tel: [phone]
Tel: [phone]
Research Triangle Park, NC 27711
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Linda Birnbaum
Sue Chang
Senior Toxicologist
3M Company
Linda A.11er
ORD/NCEA., U.S. EPA,
3M Center, 7.7.0 `F: 03
Bennett & Williams
MD B143-01
St. Paul, MN 55144
2700 E. Dublin -Granville Road
109 T. W. Alexander Drive
Tel: [phone]
Columbus, OH 43035
Research Triangle Park, NC 27709
Email: [e-mail]
Tel: [phone], X135
Tel: [phone]
Email:
Email: birnbaurn.linda @.cpa.gov
Ian Chatwell
[e-mail]
Senior Environmental Officer
Jack Bishop
Transport Canada
Stacey Anderson
Staff Scientist/Research Geneticist
620 - 800 Burrard Street
Research Scientist
NIEHS/NTP
Vancouver, British Columbia, CA
CDC/NIOSH
PO Box 12233
Tel: [phone]
1095 Willowdale Dr
RTP, NC 27709
Email: [e-mail]
Morgantown, WV 26505
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Selene Chou
Email: [e-mail]
Environmental Health Scientist
Connie Brower
Agency for Toxic Substances
Katherine Anitole
WQ Standards Coordinator
and Disease Registry
Toxicologist
State of NC
1600 Clifton Road, N.E.
I1.S. EPA
1617 Mail Service Center
ATSDR/DTEM Mailstop F32
1200 Pennsylvania Ave NW
Raleigh, NC 27699
Atlanta, GA 30333
MC 7403M
Tel: [phone], x 380
Tel: [phone]
Washington, DC 20460
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Bob Buck
Jonathan Clapp
Technical Fellow
PTFE Business Manager
Scott Bartell
DuPont
AGC Chemicals Americas, Inc.
Assistant Professor
4417 Lancaster Pike
55 E. Uwchlan Ave, Suite 201
University of California, Irvine
BMP23-2236
Exton, PA 19341
Dept. of Epidemiology
Wilmington, DE 19803
Tel: [phone]
100 Theory Room 126
Tel: [phone]
Email: [e-mail]
Irvine, CA 92697
Email:
Tel: [phone]
[e-mail]
Harvey Clewell
Email: [e-mail]
Director, Center for Human
John Butenhoff
Health Assessment
Hugh Barton
3M Company
The Hamner
Toxicologist
3M Center, 220-6W-08
6 Davis Drive
US EPA
St. Paul, MN 55144
Research Triangle Park, NC 27709
109 TW Alexander Drive
Tel: [phone]
Tel: [phone]
Research Triangle Park, NC 27711
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Craig Butt
Chris Corton
Phd student
Senior Research Biologist
Tim Begley
University of Toronto
US EPA
Chief, Methods Development Branch
80 St. George Street
109 TW Alexander Dr.
FDA
Toronto, Ontario , CA
Research Triangle Park, NC 27711
5100 Paint Branch Parkway
Tel: [phone]
Tel: [phone]
College Park, MD 20740
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email:
tiiiiothy.begley@FDA,Iihs.gov
52
DEQ-CFW 00000910

U.S. Environmental Protection Agency
PFAA Days 11 Workshop
June 3-5, 2008
Research Triangle Park, NC
Walter Cybulski
Biologist
US EPA - ORD/OSP
Ronald Reagan Building
Room 51120, MC 8104R
1200 Pennsylvania Avenue NW
Washington, DC 20460
Tel: [phone]
Email: [e-mail]
Kaberi Das
Biologist
Reproductive Toxicology
Division/NHEERL
Mail Drop 72
US EPA
Research Triangle Park, NC 27711
Tel: [phone]
Email: [e-mail]
Stephanie Davis
Epidemiologist
ATSDR
4770 Buford Highway
MS-F57
Atlanta, GA 30341
Tel: [phone]
Email: [e-mail]
Rory -Owen Delaney
CEO
Man Bites Dog Films
1000 S. Orlando Ave.
Los Angeles, CA 90035
Tel: [phone]
Fax: [e-mail]
Jessica D'eon
PhD Candidate
University of Toronto
80 St. George Street
Toronto, Ontario, CA
Tel: [phone]
Email: [e-mail]
Jamie DeWitt
Postdoctoral trainee
UNC/EPA
109 TW Alexander Dr., MDB 143-01
RTP, NC 27711
Tel: [phone]
Email: [e-mail]
Alan Ducatman
Professor, Chair
West Virginia Univ
WVU School of Medicine
Dept of Community Medicine
Morgantown, WV 0
Tel: [phone]
Email: [e-mail]
PARTICIPANT ROSTERS
Peter Egeghy
Research Environmental Scientist
US EPA National Exposure
Research Laboratory
109 TW Alexander Dr.
Mail Drop E205-04
Durham, NC 27711
Tel: [phone]
Email: [e-mail]
Dave Ehresman
3M Company
3M Center, 236-C 148
St. Paul, MN 55144
Tel: [phone]
Email: [e-mail]
Jackson Ellington
Research Chemist
US EPA/SSA
960 College Station Road
Athens, GA 30605
Tel: [phone]
Email: [e-mail]
David Evans
Publisher
Elsevier
360 Park Ave South
New York, NY 10010
Tel: [phone]
Email: [e-mail]
Cathy Fehrenbacher
Branch Chief
US EPA/OPPT
1200 Pennsylvania Ave. N.W.
(7406M)
Washington, DC 20460
Tel: [phone]
Email: [e-mail]
Suzanne Fenton
Research Biologist
US EPA
2525 Hwy 54
MD-67
Research Triangle Park, NC 27711
Tel: [phone]
Email: [e-mail]
Robert Ellis -Hutchings
Postdoctoral Trainee
Tony Fletcher
U.S. EPA
Epidemiologist
2525 East NC-54
LSHTM
Durham, NC 27713
Keppel St
Tel: [phone]
London, GB
Email:
Tel: [phone]
[e-mail]
Email: [e-mail]
Edward Emmett
Professor of Occupational Medicine
School of Medicine, Univ. of
Pennsylvania
Silverstein Pavilion, Ground Floor
3400 Spruce Street
Philadelphia, PA 19101
Tel: [phone]
Email:
emmetted@ma il.med.upenn.edu
Mindy Erickson
Research Scientist
MN Pollution Control Agency
520 Lafayette Road North
St. Paul, MN 55101
Tel: [phone]
Email: [e-mail]
Yasuo Eto
Senior Technical Manager
AGC Chemicals Americas, Inc.
55 East Uwchlan Avenue
Exton, PA
Tel: [phone]
Email: [e-mail]
53
Francesca Florey
Sr. Research Scientist
Battelle Memorial Insitiute
100 Capitola Drive
Durham, NC 27713
Tel: [phone]
Email: [e-mail]
Roy Fortmann
Acting Director
Human Exposure and Atmospheric
Sciences Division, National
Exposure Research Lab
U.S. EPA
MD205-04, 109 TW Alexander Dr.
Research Triangle Park, NC 27709
Tel: [phone]
Email: [e-mail]
DEQ-CFW 00000911

U.S. Environmental Protection Agency
PFAA Days II Workshop
June 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
Paul Foster
Tony Gemma
Zhishi Guo
Branch Chief
Scientist IV
Environmental Scientist
NIEHS/NTP
NCBA/SEEP
US EPA
PO Box 12233 (MD EC-34)
109 TW Alexander Dr.
Mail Code E305-03
Research Triangle Park, NC 27709
Research Triangle Park, NC 27711
RTP, NC 27711
Tel: [phone]
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Email: [e-mail]
Email: [e-mail]
John Fowle
Dori Germolec
Romona Haebler
Acting Director, NTD
Immunology Discipline Leader
Veterinary Medical Officer
US EPA / ORD/NHEERL
NTP/NIEHS
US EPA
109 TW Alexander Drive
79 Alexander Drive
27 Tarzweli Dr.
MD 105-03
Durham, NC 27713
Narragansett, R1 2882
RTP, NC 27711
Tel: [phone]
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Email: [e-mail]
Email: [e-mail]
Helen Goeden
Kimberly Harris
Elaine Francis
Research Scientist
Life Scientist
National Program Director
Minnesota Department of Health
US EPA - Region 5
US EPA
625 Rohert St, N
77 W. Jackson Boulevard
1200 Pennsylvania Avenue, NW
P.O. Box 64975
WG-15J
(8101 R)
St. P an 1, MN 0
Chicago, IL 60604
Washington, DC 20460
Tel: [phone]
Tel: [phone]
Tel: [phone]
Email:
Email: [e-mail]
Email: [e-mail]
helen.goeden@health. state.mn.us
Lynne Harris
Jennifer Franco
Michael -Rock Goldsmith
Senior Vice President
Research Scientist
Research Physical Scientist
SPI
CDC/NIOSH
US -EPA / NERL-HEASD / EDRB
1667 K Street NW, Ste. 1000
1095 Willowdale Dr
109 TW Alexander Dr.,
Washington, DC 22181
Morgantown, WV 26505
MD E205-01
Tel: [phone]
Tel: [phone]
RTP, NC 27711
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Amy Hartford
Jeffrey Frithsen
Attorney
Supervisory Biologist
David Gray
D. David Altman Co., LPA
USEPA - ORD - NCEA - 8623P
Toxicology Program Director
15 E. 8th Street, Suite 20OW
1200 Pennsylvania Avenue, NW
Tetra Tech Inc.
Cincinnati, OH 45202
Washington, DC 20460
10306 Eaton Place, Suite 340
Tel: [phone]
Tel: [phone]
Fairfax, VA 22030
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Sandra Z. Haslam
Michael Gage
Professor
SEE scientist
Mark Greenwood
Michigan State University
US EPA
Ropes&.Gray
Department of Physiology
NHEERL, MD-67
One Metro Center
2201 Biomedical & Physical
RTP, NC 27711
700 12th Street. NW, Suite 900
Sciences Bldg
UTel: 919-541-1309
Washington, DC 20005
East Lansing, MI 48824
Email: [e-mail]
Tel: [phone]
Tel: [phone] X1154
Email:
Email: [e-mail]
Andrew Geller
[e-mail]
Asst. Laboratory Director
Martin Healy
U.S. EPA/ NHEERL/ORD
Robert Griffin
Associate
Mail Code: B305-02
General Manager
W. L. Gore & Associates, Inc.
Research Triangle Park, NC 27711
Little Hocking Water Association
501 Vi"", Way
Tel: [phone]
P.O. Box 188
Elkton, MD 21921
Email: [e-mail]
3998 State Route 124
Tel: [phone]
Little Hocking, OH 45742
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
54
DEQ-CFW 00000912

U.S. Environmental Protection Agency
PFAA Days II Workshop
June 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
John Heinze
Elaine Cohen Hubal
Deborah Keil
Senior Science Advisor
NCCT/ EPA
Associate Professor
Fluoropolymer Products
RTP, NC 27711
UNLV
Information Center
Tel: [phone]
Clinical Laboratory Sciences, 4505
529 14th Street, NW, Suite 807
Email: [e-mail]
Maryland Parkway
Washington, DC 20045
Box 453021
Tel: [phone]
Sid Hunter
Las Vegas, NV 89154
Email: jheinze@ehrfinfo
Acting Division Director
Tel: [phone]
US EPA
Email: [e-mail]
Laurence Helfant
Reproductive Toxicology
Scientist
Division/NHEERL/ORD
Jennifer Keller
U.S. EPA
Mail Drop 71
Biologist
109 TW Alexander Drive
Research Triangle Park, NC 27711
National Institute of Standards and
Research Triangle Park, NC 27711
Tel: [phone]
Technology
Tel: [phone]
Email: [e-mail]
Hollings Marine Laboratory
Email: [e-mail]
331 Ft. Johnson Rd.
Thomas Jenkins
Charleston, SC 29412
Barbara Henry
Research Chemist
Tel: [phone]
Associate
USEPA
Email: - [e-mail]
W. L. Gore & Associates Inc.
960 College Station Road
501 Vieves Way
Athens, GA 30605
James Kelly
Elkton, MD 21921
Research Scientist
Tel: [phone]
Mary Kaiser
Minnesota Department of Health
Email: [e-mail]
Senior Research Fellow
625 Robert St. N
DuPont
PO Box 64975
Ross Highsmith
E402/5321
St. Paul, MN 55164
ALD
P.O. Box 80402
Tel: [phone]
NERL/EPA
Wilmington, DE 0
Email: [e-mail]
MD 305-01
Tel: [phone]
RTP, NC 27711
Email:
Gerald Kennedy
Tel: [phone]
[e-mail]
Toxicologist
Email: [e-mail]
Haskell Lab/DuPont Company
Kurunthachalam Kannan
1080 Elkton Road
Erin Hines
Professor
Newark, DE 19714
Postdoc Biologist
Wadsworth Center, New York State
Tel: [phone]
US EPA
Department of Health
Email:
US EPA MD-67
Empire State Plaza
[e-mail]
RTP, NC 27713
P.O. Box 509
Tel: [phone]
Albany, NY 12201
Tara Siemens Kennedy
Email: [e-mail]
Tel: [phone]
Environmental Toxicologist
Email: [e-mail]
SLR Consulting (Canada) Ltd.
Colette Hodes
200-1620 West 8th Ave
Toxicologist
Myra Karstadt
Vancouver, British Columbia, CA
OPPT/RAD/ECAB
Adjunct Assistant Professor
Tel: [phone]
1200 Pennsylvannia Ave.
Drexel University School of
Email: [e-mail]
MC 7403M
Public Health
Washington, DC 20460
6722 Hillandale Road
Kirk Kitchin
Tel: [phone]
Chevy Chase, MD 20815
US EPA
Email: [e-mail]
UTel: 301-652-1540
Mail Code: B143-06
Email: [e-mail]
RTP, NC
Jiirgen Holzer
Tel: [phone]
Ruhr -University Bochum
Robert Kavlock
Email: [e-mail]
Department for Hygiene, Social and
Director
Environmental Medicine
NCCT
Thomas Knudsen
MA 1/33, Universitaetsstrasse 150
B-205-01
Developmental Systems Biologist
Bochum, 44801 DE
US EPA
U.S. EPA National Center for
Tel: [phone]
RTP, NC 27711
Computational Toxicology
Email: [e-mail]
Tel: [phone]
B205
Email: [e-mail]
Research Triangle Park, NC 27711
Tel: [phone]
Email: [e-mail]
N17
DEQ-CFW 00000913

U.S. Environmental Protection Agency
PFAA Days II Workshop
.Tune 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
Volker Koch
Richard Leukroth
Christopher Lyu
Environmental Safety Assessment
Chemist / Toxicologist
Associate Director
Clariant DE Corporate
US EPA
Battelle/Centers for Public Health
Product Safety
1200 Pennsylvania Avenue, N.W.
Research & Evaluation
Am Unisys -Park 1
Mail Stop 7405
100 Capitola Drive, Suite 200
Sulzbach, 65843 DE
Washington, DC 20460
Durham, NC 27713
Tel: [phone]e+012
Tel: [phone]
Tel: [phone]
Email:
Email: [e-mail]
Email:
[e-mail]
[e-mail]
Laurence Libelo
Toni Krasnic
Environmental Engineer
Scott Mabury
Biologist
EPA/OPPTS/OPPT/EETD/E,AB
Professor
CCD/OPPT/OPPTS/US EPA
1200 Penn Ave NW
Dept. of Chemistry, Univ. of Toronto
Mail Code 7405M
MC 7406M
TO-OSt. George Street
Ariel Rios Building
Washington, DC 20460
Toronto, Ontario CA
1200 Pennsylvania Ave., NW
Tel: [phone]
Tel: [phone]
Washington, DC 20460
Email: [e-mail]
Email:
Tel: [phone]
[e-mail]
Email: [e-mail]
Andy Lindstrom
USEPA
Susan Makris
Ken Krebs
Mail Code: E205-04
Toxicologist
Chemist
R'I P, NC, NC 27701
US EPA, ORD, NCEA-W
US EPA
Tel: [phone]
1200 Pennsylvania Ave., NW
Mail Code E305-03
Email: [e-mail]
Mail Code: 8623P
RTP, NC 27711
Washington, DC 20460
Tel: [phone]
Xiaoyu Liu
Tel: [phone]
Email: [e-mail]
Chemist
Email: [e-mail]
US EPA
David Lai
109 T.W. Alexander Drive
Edward Massaro
Toxicologist
Durham, NC 27711
Toxicologist
US EPA
Tel: [phone]
USEPA/RTP/RTD/DBB/MD-67
1200 Pennsylvania Ave., N.W.
Email: [e-mail]
Durham, NC 27713
Washington, DC 20460
Tel: [phone]
Tel: [phone]
Matthew Lorber
Email: [e-mail]
Email: [e-mail]
Senior Environmental Engineer
NCEA/ORD/EPA
Elizabeth Maull
Edward Lampert
NCEA (8623P)
Program Administrator
Lampert&Associates
1200 Pennsylvania Ave, NW
NIEHS
3-15-11-940 Roppongi
Washington, DC 20460
PO Box 12233 (MD EC21)
Minato-ku
Tel: [phone]
RTP, NC 27709
Tokyo, Japan
Email: [e-mail]
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Email:
Mike Luster
[e-mail]
Senior Advisor
Jean Meade
NIOSII
Research Scientist
Christopher Lau
1095 Willowdale Rd
CDC/NIOSH
Lead Research Biologist
Morgantown, WV 26505
1095 Willowdale Dr
Reproductive Toxicology
Tel: [phone]
Morgantown, WV 26505
Division/NHEERL/ US EPA
Email: [e-mail]
Tel: [phone]
Mail Drop 67
Email: [e-mail]
Research Triangle Park, NC 27711
Callie Lyons
Tel: [phone]
Journalist/Author
Ronald Melnick
Email: [e-mail]
WMOA/WJAW
Toxicologist
1005 Lancaster Street
National Toxicology
Holly Lee
Marietta, OH 45750
Program/NIEHS
Student
Tel: [phone]
Division of Intramural Research,
University of Toronto
Email: [e-mail]
NIEHS
80 St. George Street
MD EC-14, P.O. Box 12233
Toronto, Ontario , CA
Research Triangle Park, NC 27709
Tel: [phone]
Tel: [phone]
Fnlail: [e-mail]
Email: ❑[e-mail]:,gov
56
DEQ-CFW 00000914

U.S. Environmental Protection Agency
PFAA Days II Workshop
June 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
David Menotti
Edward Ohanian
Susan Pinney
Partner
Director, Health and Ecological
Associate Professor
Pillsbury
Criteria Division
University of Cincinnati Dept. of
2300 N Street NW
US EPA
Environmental Health
Washington, DC 20037
Office of Water (4304T)
PO Box 670056
Tel: [phone]
1200 Pennsylvanian Avenue, NW
Cincinnati, OH 0
Email:
Washington, DC 20460
Tel: [phone]
[e-mail]
Tel: [phone]
Email: [e-mail]
Email: [e-mail]
George Millet
Gloria Post
QEHS Director
Fardin Oliaei
Research Scientist
Dyneon/3M
Research Scientist
NJDEP
6744 33rd St.
Mote Marine Laboratory
PO Box 409
Oakdale, MN 550128
Sarasota, FL 34236
Trenton, NJ 8625
Tel: [phone]
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Email: [e-mail]
Email:
[e-mail]
Bruce Mintz
Geary Olsen
Asst Lab Director for Water
Staff Scientist
Julian Preston
EPA ORD/NERL
3M
Acting ADH
107 TW Alexander Dr
Medical Dept
U.S. EPA
RTP, NC 27709
Mail Stop 220-6W-08
NHEERL (B105-01)
Tel: [phone]
St. Paul, MN 55144
Research Triangle Park, NC 27711
Email: [e-mail]
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Email: [e-mail]
Leonard Mole
Research Chemist
Margie Peden -Adams
James Rabinowitz
US EPA
Asst. Prof.
Senior Scientist, NCCT/ORD
MD 72, NHEERL
MUSC
Mail Code 343-03
US EPA
221 Ft. Johnson Rd.
U.S. Environmental Protection
RTP, NC 27511
Charleston, SC 29412
Agency
Tel: [phone]
Tel: [phone]
Research Triangle Park, NC 27711
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Shoji Nakayama
Jeffrey Peters
Research Participant
Associate Professor
Amy Rand
US EPA / NERL / HEASD
Pennsylvania State University
Graduate Student
MD: E205-04
312 Life Science Building
University of Toronto
Research Triangle Park, NC 27511
University Park, PA 16802
80 St. George St.
Tel: [phone]
Tel: [phone]
Toronto, Ontario, CA
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Retha Newbold
Terry Peters
Developmental Biologist
Executive Director
William Reagen
N1EHS/NIH
FPD
Laboratory Manager
Alexander Drive
1667 K Street NW, Suite 1000
3M
Building 101, Mail drop E4-02
Washington, DC 20006
3M Center, Bldg 260-05-N-17
Research Triangle Park, NC 27709
Tel: [phone]
St. Paul, MN
Tel: [phone]
Email: [e-mail]
Tel: [phone]
Email: newboldl@niehs,nih,gov
Email: wkreagen@.mnun.com
Andrea Pfahles-Hutchens
Lynda Nolan
Epidemiologist
Jessica Reiner
Advanced Practice Nurse
US EPA
Postdoctoral Fellow
Practitioner
1200 Pennsylvania Ave., NW
USEPA
University of Pennsylvania
7403M
Human Exposure and Atmospheric
4 Evana Road
Washington, DC 20460
Sciences Division
East Brunswick, NJ 8816
Tel: [phone]
Mail Drop: E205-04
Tel: [phone]
Email:
Research Triangle Park, NC 27711
Email: [e-mail]
[e-mail]
Tel: [phone]
Email: [e-mail]
57
DEQ-CFW 00000915

U.S. Environmental Protection Agency
PFAA Days II Workshop
June 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
Katherine Rhyne
Mitch Rosen
Jennifer Seed
King & Spalding
Research Biologist
Branch Chief
1700 Pennsylvania Ave. NW
Reproductive Toxicology
US EPA
Suite 200
Division/NHEERL
1200 Pennsylvania Ave NW
Washington, DC 20006
Mail Drop 67
Washington, DC 20460
Tel: [phone]
US EPA
Tel: [phone]
Email: [e-mail]
Research Triangle Park, NC 27711
Email: [e-mail]
Tel: [phone]
Penelope Rice
Email: [e-mail]
Irnran Shah
Toxicologist
US EPA
U.S. FDA/Division of Food
Erin Russell
109 TW Alexander Dr, B20501
Contact Notifications
TRP Representative
RTP, NC 27516
5100 Paint Branch Parkway
Clariant
Tel: [phone]
HFS-275
4000 Monroe Road
Entail: [e-mail]
College Park, MD 20740
Charlotte, NC 28205
Tel: [phone]
Tel: [phone]
Laura Solem
Email:
Email: [e-mail]
Toxicologist
[e-mail]
Minnesota Pollution Control Agency
William Russo
525 Lake Ave South, Suite 400
Robert Rickard
Assistant Laboratory Director for
Duluth, MN 55802
Science Director - Health and
Water & Land Programs
Tel: [phone]
Environmental Scienc
U.S. EPA/NHEERL/ORD
Email:
DuPont
Mail Code: B305-02
[e-mail]
DuPont CRP 708/111
4930 Old Page Rd.
4417 Lancaster Pike
Research Triangle Park, NC 27709
Bob Stallings
Wilmington, DE 19805
Tel: [phone]
Environmental Engineer
Tel: [phone]
Email: [e-mail]
US EPA
Email:
109 T W Alexander
[e-mail]
Carin Sakr
Research Triangle Park, NC 27711
Occupatinnal Medicine Physician
Tel: [phone]
Chester Rodriguez
DuPont Epidemiology Program
Email: [e-mail]
Biologist
1090 Elkton Road
US EPA
Newark, DE 19714
Jason Stanko
109 TW Alexander Drive
Email:
USEPA NHEERL
Research Triangle Park, NC 27703
[e-mail]
2525 E Hwy 54
Tel: [phone]
Durham, NC 27713
Email:
David Sanders
Tel: [phone]
[e-mail]
Environmental Engineer
Email: [e-mail]
U.S. EPA
John Rogers
C539-01
Kyle Steenland
Chief, Developmental
109 TW Alexander Drive
Professor
Biology Branch
Research Triangle Park, NC 27711
Rollins Sell Pub Hlth, Emory U
U.S. EPA
Tel: [phone]
1518 Clifton Rd
MD-67
Email: [e-mail]
Atlanta, GA 30322
Research Triangle Panic, NC 27711
Tel: [phone]
Tel: [phone]
David Sarvadi
Email: [e-mail]
Email: [e-mail]
Keller and llcckman lip
1001 G Street NW
Mark Sttynar
Jacky Rosati
Washington, DC 20001
Physical Scientist
Environmental Scientist
Tel: [phone]
USEPA/ORD/NERL
U.S. EPA
Email: [e-mail]
109 T.W. Alexander Dr.
109 TW Alexander Drive
Durham, NC 27711
E343-06
Jay Schulz
Tel: [phone]
Research Triangle Park, NC 27711
Regulatory Affairs Specialist
Email: [e-mail]
Tel: [phone]
3M
Email: [e-mail]
3M Center
Adam Swank
Bldg. 236-1 B-10
Chemist
St. Paul, MN 55144
U.S. EPA/NHEERL-ACC/ORD
Tel: [phone]
Mail Code: D305-02
Email: [e-mail]
Research Triangle Park, NC 27711 _
Tel: [phone]
Email: [e-mail]
58
DEQ-CFW 00000916

U.S. Environmental Protection Agency
PFAA Days II Workshop
June 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
J. Morel Symons
Veronica Vieira
Richard Wiggins
Supervisor, Research
Assistant Professor
EPA/ORD/NHEERL
and Development
Boston University School of
MD B305-02
DuPont Epidemiology Program
Public Health
RTP, NC 27711
1090 Elkton Road, P.O. Box 50
715 Albany Street
Tel: [phone]
Newark, DE 19714
Talbot 4W
Email: [e-mail]
Tel: [phone]
Boston, MA 2072
Email:
Tel: [phone]
John Wilson
[e-mail]
Email: [e-mail]
Research Microbiologist
U.S. EPA
Cecilia Tan
Teresa Wall
R.S. Environ. Res. Center
The Hamner Institutes
Program Analyst
919 Research Drive
6 Davis Drive
NHEERL, ORD, US EPA
Ada, OK 74820
PO Box 12137
Research Triangle Park, NC 27711
Tel: [phone]
Research Triangle Park, NC 27709
Tel: [phone]
Email: [e-mail]
Tel: [phone]
E-mail: [e-mail]
Email: [e-mail]
Douglas Wolf
John Wambaugh
Assistant Laboratory Director
Katoria Tatum
Post -doctoral Researcher
NHEERL/ORD/USEPA
Post -doe
US EPA, National Center for
MD B305-02
UNC/EPA
Computational Toxicology
109 Alexander
2525 Highway 54 E
109 T.W. Alexander Dr.
Research Triangle Park, NC 27711
Durham, NC 27713
Mail Code D343-03
Tel: [phone]
Tel: [phone]
Researtch Triangle Park, NC 27711
Email: [e-mail]
Email: [e-mail]
Tel: [phone]
Email: [e-mail]
Cynthia Wolf
Kevin Teichman
US EPA
Deputy Assistant Administrator
John Washington
109 TW Alexander Drive
for Science
Research Chemist
MD-67
U.S. EPA
US EPA
Research Triangle Park, NC 27711
1200 Pennsylvania Ave., NW
960 College Station Road
Tel: [phone]
Washington, DC 20004
Athens, GA 30605
Email: [e-mail]
Tel: [phone]
Tel: [phone]
Email: [e-mail]
Email:
Robert S. Wright
[e-mail]
Chemist
Kent Thomas
US EPA
Acting Branch Chief
John Wathen
Mail Code E343-03
EPA/ORD/NERL/HEASD/EMAB
Asst. Branch Chief
109 TW Alexander Drive
MD E205-04
EPA-OW-OST
Research Triangle Park, NC 27711
Research Triangle Park, NC 27711
1300 Pennsylvania Ave
Tel: [phone]
Tel: [phone]
Mail Code 4305T
Email: [e-mail]
Email: [e-mail]
Washington, DC 20460
Tel: [phone]
Tai-Teh Wu
Takashi Tozuka
Email: [e-mail]
Principal Scientist
Daikin Industries, LTD
Bayer CropScience
Umeda Center Bldg.,
Clement Welsh
8400 Hawthorne RD
2-4-12, Nakazaki-Nishi, Kita-ku,
ATSDR
Kansas City, MO 64120
Osaka, Japan
4770 Buford Highway
Tel: [phone]
Tel: [phone]
Mail Stop F-58
Email:
Email:
Atlanta, GA 30341
Tai-Tell.Wr](&bayer'CrOpsclence.coiii
[e-mail]
Tel: [phone]
Email: [e-mail]
Chengfeng Yang
Pablo Jorge Tseng
Assistant Professor
Graduate Student
Sally White
Michigan State University
University of Toronto
Predoctoral Trainee
Department of Physiology
80 St. George Street
US EPA ORD RTD
4171 Biomedical Physical Sceicnes
Toronto, Ontario, CA
Durham, NC
East Lansing, MI 48824
Tel: [phone]
Tel: [phone]
Tel: [phone], ext1139
Email: [e-mail]
Email: [e-mail]
Email: [e-mail]
59
DEQ-CFW 00000917

U.S.. Environmental Protection Agency
PFAA, Days II Workshop
.Tune 3-5, 2008
Research Triangle Park, NC
PARTICIPANT ROSTERS
Hoon Yoo
Research Chemist
T iSEPA/SEE
960 College Station Road
Athens, GA 30605
Dan Zehr
SEE Employee
U.S. EPA
2525 Hwy 54
Durham, NC 27713
Tel: [phone]
Email:
[e-mail]
Harold Zenick
Laboratory Director
NHEERL/ORD/US EPA
Mail Code B305-01
Research Triangle Park, NC 27711
Tel: [phone]
Email; zenick.hai(vepa.gov
Larry Zobel
Vice President & Medical Director
3M
3M Medical Department
3M Center, Bldg. 220-6W-08
St. Paul, MN 55144
Tel: [phone]
Email: [e-mail]
DEQ-CFW 00000918