CSS Research News and Highlights
AUGUST 2014
CSS Highlights
EPA Paper Published in Nature Biotechnology: Phenotypic screening of the ToxCast
chemical library to classify toxic and therapeutic mechanisms
EPA scientists recently published a paper on high
throughput toxicology research in Nature Biotechnology
that showcased how ToxCast might be used to predict the
potential toxicity of chemicals. EPA researchers analyzed the
screening results generated by one of its assay technologies,
BioSeek, and compared the results to known chemical
information to determine if this new technology can be
used to predict the potential toxicity and therapeutic effect
of 776 chemicals found in pharmaceuticals, pesticides, and
other commonly used consumer products.
The paper describes the analysis of all screening results and
then compares them to animal toxicity studies and other established toxicity information, demonstrating that
these new technologies can be used to predict potential health hazards. The authors also explain that the
screening results provide information on how the chemicals interact with exposed cells and which important
biological processes may be impacted.
The paper is available on the publisher's website.
Visit the ToxCast website to learn more about the EPA ToxCast program.
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EPA Paper Awarded "Top Five Best Papers" in SETAC Journal 2013
EPA researcher Carlie LaLone's paper titled, Cross species
sensitivity to a novel androgen receptor agonist of potential
environmental concern, spironolactone has been awarded "Best
Paper Award Finalist" by the Society of Environmental
Toxicology and Chemistry (SETAC) for 2013. This paper was
among 5 nominated articles for "Best Paper Award."
Environmental Toxicology and Chemistry (ET&C) will be
publishing a list of the top 5 articles as well as a piece on the
winner of the "Best Paper Award" in the July 2014 issue. The
paper studied the effects of spironolactone, a pharmaceutical
drug that affects the androgen receptor, on vertebrates and
invertebrates. More importantly this paper demonstrates how
prior knowledge of adverse outcome pathways (AOPs) and the
conservation of a key molecular target across vertebrates can Figure from LaLone, etai 2013
be utilized to identify potential chemicals of concern for
monitoring and highlight potentially sensitive species and endpoints for testing. This paper presents one of
several CSS studies evaluating the applications of AOPs to transform and enable predictivity in chemical safety
evaluations.
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Non-Monotonic Dose Response Curve (NMDRC)
The National Academy of Sciences released their review of EPA's State-of-the-Science Evaluation of
Nonmonotonic Dose-Response Relationships as They Apply to Endocrine Disruptors. This report is the
Agency's first step towards an evaluation of the state of the science and informed understanding of NMDRs
and their implications to chemical testing strategies. EPA is currently reviewing the NAS recommendations
and will determine the next steps for addressing their findings and recommendations. There is more
information available on EPA's NMDRC report webpage.
Non-Monotonic Curves
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CSS Program in Review
Joint Science Advisory Board (SAB) and Board of Scientific Counselors (BOSC)
Meeting - July 24-25
The SAB and BOSC met July 24-25 to evaluate preliminary outlines of EPA's Office of Research and
Development's (ORD) FY16-19 Strategic Research Action Plans (StRAPs) for the National Research Programs
(NRPs). The six research programs (ACE. CSS, SSWR, HHRA. HS. and SHC) provided overviews of their strategic
direction, soliciting feedback from the SAB and BOSC advisory members.
In addition, the advisory members provided feedback on four ORD cross-cutting research roadmaps which
include: the Children's Environmental Health Roadmap led by Elaine Cohen Hubal of CSS, Global Climate
Change led by Andy Miller of ACE, Nitrogen and Co-pollutants led by Anna Rea of SSWR, and Environmental
Justice led by Mary Manibusan of OSP,
This meeting provided the opportunity to solicit early input on each NRP's strategic direction and seek
feedback on the strength of cross-program integration either explicitly through the cross-cutting roadmaps, or
through coordinated research activities. Plenary and breakout group discussions provided rich feedback to the
National Program Directors, who will begin to address these as they evolve the StRAPs and roadmaps in FY 14-
15.
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FIFRA Scientific Advisory Panel Meeting - July 29-30
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory
Panel (SAP) met July 29-30, 2014 to hear presentations from EPA researchers
about using high-throughput exposure estimates to prioritize chemicals for
potential endocrine disruption. The SAP was convened by EPA's Endocrine
Disruption Screening Program (EDSP). EPA's EDSP is charged with determining
whether chemicals disrupt estrogen (direct female reproduction and
development), androgen (direct male reproduction and development) and
thyroid hormones (important to brain development). EDSP is interested in using
high-throughput exposure estimates from EPA's Chemical Safety for
Sustainability Research Program to inform prioritization of the thousands of chemicals of interest for testing.
To ensure these results are scientifically sound and relevant the SAP was asked to provide recommendations
to EPA about using these new approaches. The SAP's initial comments were positive and supportive, and their
report with specific evaluations and comments will be issued in approximately 90 days. More information is
available at: http://www.epa.gov/scipoly/sap/meetings/2014/072914meeting.html
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Upcoming Events & Meeting Announcements
ToxCast Data Summit - September 29-30 at EPA in Research Triangle Park, NC
Do you have ideas of how the ToxCast high-throughput screening data can be used? We want YOU to submit
your ideas in an abstract for this event! It is not necessary to have any detailed or published work in order to
attend. This Data Summit encourages discussion, collaboration, and feedback about the ideas presented, and
also on EPA's work with the Data and iCSS Dashboard. Abstracts are due August 1. Please see the Data Summit
website for more information.
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EPA @ Upcoming International Society of Exposure Science
(ISES) Meeting
The EPA will be participating in the 24th Annual International Society of
Exposure Science (ISES) Meeting coming up on October 12-16, 2014 in
Cincinnati, Ohio. The theme for this year is Exposure Science Integration to
Protect Ecological Systems, Human Well-Being, and Occupational Health, with
the Agency's own Dr. Tim Buckley and Dr. Lisa Jo Melnyk serving as meeting
chairs.
Additionally, Dr. Buckley will be co-chairing and speaking at one of the
symposia on the development of predictive models from big data. EPA scientist Dr. Kristin Isaacs will also co-
chair a session titled, "The ExpoDat Initiative: Exposure-Informed Chemical Safety Assessment for High
Throughput Prioritization," during which she will present on the Stochastic Human Exposure and Dose
Simulation High Throughput (SHEDS-HT) Model, alongside Dr. John Wambaugh, who will discuss the use of
EPA's ExpoCast Framework for rapid exposure forecasts.
Conference attendees can also check out the Agency exhibit booth and some of the pre-conference
workshops instructed by EPA staff. To learn more, visit the meeting website at: http://www.ises2014.org/.
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EPA Scientists to Present at 9th World Congress on Alternatives and Animal Use in
the Life Sciences Meeting - August 24-28 in Prague, Czech Republic
Dr. Bob Kavlock, Deputy Assistant Administrator for Science of the Office of
Research and Development, is a Keynote Speaker at the 2014 WC9 meeting.
He will be discussing the US Toxicology in the 21st Century (Tox21 Program,
a federal collaboration between EPA, NIEHS/NTP, NCATS, and FDA. Several
EPA scientists are leading the organization of sessions at the Congress and
will present transformative applications of EPA research on alternatives and
animal use in life science research. These include: Dr. Thomas Knudsen on virtual tissue models, Dr. Bill Mundy
on high-content imaging, Dr. Richard Judson on predictive biology, Dr. Keith Houck on nanomaterials risk
assessment, Dr. Ann Richard on computational modeling and chem-informatics, and Dr. John Wambaugh on
exposure. Dr. David Dix will also be chairing two sessions on Endocrine Disruption and Chemical Regulation.
Please visit the meeting agenda for additional presentations by EPA experts and more detailed information.
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20 H
NINTH WORLD CONGRESS
ALTERNATIVES CONGRESS TRUST
AOP Scientific Workshop - September 3-5, 2014
Scientific Workshop
The National Toxicology Program (NTP) and Physicians
Committee for Responsible Medicine (PCRM) are hosting a
public scientific workshop, Adverse Outcome Pathways: From
Research to Regulation, on September 3-5, 2014 in Bethesda,
MD. The workshop will feature a diverse group of speakers from
government, academia and industry, including EPA staff
Stephen Edwards, David Dix, Dan Villeneuve, John Wambaugh, Shannon Bell, Rita Shoeny and Robert Devlin.
For more information on the workshop, visit; http://ntp.niehs.nih.gov/go/41374.
Adverse Outcome Pathways:
From Research to Regulation
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Previous Events & Meetings
EPA Hosts Networks for Characterizing Chemical Life Cycle (NCCLC) and Networks
for Sustainable Molecular Design and Synthesis (NSMDS) Grantees Kick-Off Meeting
On June 23-24, 2014, EPA hosted a kick-off meeting for grants recently awarded to academic institutions to
form two research networks: the Networks for Characterizing Chemical Life Cycle (NCCLC) and the Networks
for Sustainable Molecular Design and Synthesis (NSMDS). These grants were funded through a joint
collaboration between EPA and the National Science Foundation. During the meeting, lead researchers from
both Networks presented their project plans, and EPA lead researchers presented their ongoing research in
these areas. The NCCLC grant recipients include University of California, Santa Barbara and Arizona State
University. For more information on these grants, visit the NCER webpage. The NSMD grant recipients include
Yale University, University of Kansas, University of Arizona, and Colorado State University. For more
information on these grants, visit the NSF website.
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Green Chemistry & Engineering Conference
EPA had a large presence at the American Chemical
Society (ACS) Green Chemistry Institute's 18th
Design sessions, titled "Knowledge and Tools to Evaluate Alternatives." Several EPA scientists also presented
over the three-day conference, including Dr. Paul Harten, who promoted EPA's Program for Assisting the
Replacement of Industrial Solvents (PARIS III) software tool, and Keith Houck, who spoke about ToxCast in the
workshop on "Making Tools for Safer Chemical Design Work for You."
Be sure to check out conference video presentations, including a video of Dr. Harten explaining PARIS III on
the ACS Green Chemistry Institute YouTube Channel:
https;//www.youtube.com/plavlist?list=PLLIMW6nMYOanSaqvidWi CDs7taatrjhr
Advancing Chemistry. ? s
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Innovating
for Sustainability
Annual Green Chemistry and Engineering
Conference on June 17-19, 2014. CSS National
Program Director (NPD) Dr. Tina Bahadori served as
one of the co-chairs on the conference organizing
committee, along with Deputy NPD Dr. Elaine
Cohen Hubal who chaired one of the Chemical
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International OECD meeting for Validating Testing Standards for Engineered
Nanoparticles
Dr. William K. Boyes participated in the Organization for Economic Cooperative
Development (OECD) Working Party on Manufactured Nanoparticles June 4-5
meeting. At the meeting, two sub-committees: the Steering Group on Testing
and Assessment of Manufactured Nanomaterials (SG-TA) and the Steering Group
on Risk Assessment and Regulatory Programs (SG-AP) met to discuss approaches
for validating testing standards for engineered nanomaterials. The SG-TA is
developing several relevant test guidelines for ENMs including: Inhalation Test
Guidelines and Guidance to Accommodate Nanomaterials, Aquatic and
Sediment Toxicology Testing of nanomaterials, Dissolution Rate of
Nanomaterials in the Aquatic Environment, Test Guidance for Nanomaterials
Removal from Wastewater, Dispersion and Dissolution of Nanomaterials in Aquatic Media - Decision tree,
Assessing the Apparent Accumulation Potential of Nanomaterials, and Dispersibility and Dispersion Behavior
of Nanomaterials in Aquatic Media. Several international partnerships were discussed including NanoReg, a
common European approach to regulatory testing; a Canada-US Regulatory Cooperation Council; and a
Business and Industry Advisory Committee (BIAC) to the OECD. Stay Current on EPA's Nanomaterials Research
- visit the nanomaterials research webpage.
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Funding & Employment Opportunities
EPA is Accepting Applications for ORISE Postdoctoral Positions
As part of the Oak Ridge Institute for Science and Education (ORISE) Internship/Research Positions Program,
EPA is accepting applications for a number of Chemical Safety for Sustainability (CSS) centric positions across
several EPA labs and centers including: the National Health Effects Research Lab (NHEERL), the National
Exposure Research Lab (NERL), the National Center for Environmental Assessment (NCEA), the National Risk
Management Research Lab (NRMRL), and the National Center for Computational Toxicology (NCCT), Some
postdoctoral positions from the various labs and centers are listed below, but there are many more on the
ORISE Current EPA Research Opportunities page.
• Sustainable Synthesis and Applications of
Nanomaterials and Nanocomposites
• Application of Computational Chemistry to
Predictive Toxicity Modeling
• Chemical Safety for Sustainability
• Human Behavioral Exposure
• Applying Novel Data Streams to Advance
Human Health Risk Assessment
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Chemical Safety Research in the News
Recent News Articles
• EPA Advisers Endorse Agency's Draft Plans to Research Air, Chemicals arid
Other Topics
• EPA Strategies to Promote Rapid Analysis of Toxicity. Life Cycle Impacts to Be
Critiqued
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let us know by contacting LaCresha Styles (styles. Iacresha(5)epa .gov).
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