EPA 601/R-17/001 I October 2016 I www.epa.gov/research
Children's
Environmental Health
RESEARCH ROADMAP
FY16 ANNUAL REPORT
V
Office of Research and Development
Research Roadmap: Children's Environmental Health
FY]6 Annual Report
&EPA
United States
Environmental Protection
Agency
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Contents
Authors and Contributors iii
Children's Environmental Health Implementation Working Group Members iv
Abbreviations and Acronyms v
Executive Summary vi
I, Accomplishments 1
A. Impacts of ORD CEH Research on EPA Decisions 1
Certification of Pesticide Applicators 2
Organophosphates - Retention of Safety Factor 2
Endocrine Disruptor Screening Program (EDSP) 2
Microcephaly and Zika Virus 2
Recycled Tire Crumbs and Health Risks 3
Remediating Lead Contamination in Drinking Water 3
Perchlorate Dose-Response Modeling 4
B. Integration of CEH Research for Impact Delivery 4
Virtual Tissues Modeling Research Project - Integrating EPA's Intramural and
Extramural Research 4
Developmental Health - Integrating across ORD and with Program and Regional
Partners 5
Safe Drinking Water - The Lead Example: Integrating across Policy Domains 6
Indoor Air and Health - Emerging Area of Integration 6
C. Outreach to Partners and Stakeholders 7
Scientific and Advisory Bodies 7
Program Offices and Regions 8
Current List of Products/Peer-Reviewed Publications 9
D. Encouraging Innovation 9
Pathfinder Innovation Projects 9
Smart Acceleration of Research Through Investment Awards 10
Science to Achieve Results (STAR) Grants 10
E. Challenges & Opportunities 19
Changes in the Broader Scientific and Policy Landscape with Impact on CEH Research 19
Improving Integration of Research Projects across ORD 20
II, The Year Ahead 21
A. Near-term Research Efforts 21
B. Proposed Meetings and Workshops 21
Appendix A. Completed Peer-Reviewed ORD Publications in FY16 A-l
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Authors and Contributors
Roadmap Lead
John Cowden
Office of Research and Development
Lead Author
Benjamin Zukowski
Office of Research and Development
Contribute?! 'in Iph ibeti>vjI oider)
Tina Bahadori
Office of Research and Development
Susanna Blair
Office of Research and Development
Michael Firestone
Office of Children's Health Protection
William Fisher
Office of Research and Development
Lynn Flowers
Office of Research and Development
Jill Franzosa
Office of Research and Development
Dayna Gibbons
Office of Research and Development
Annette Guiseppi-Elie
Office of Research and Development
Monica Linnenbrink
Office of Research and Development
Nica Louie
Office of Research and Development
Kelsey Maloney
Office of Research and Development
NicolleTulve
Office of Research and Development
Valerie Zartarian
Office of Research and Development
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Children's Environmental Health Implementation Working
Group Members
Working Group Leads
Jill Franzosa
Office of Research and Development, U.S. EPA
NicolleTulve
Office of Research and Development, U.S. EPA
Working Group Members (in alphabetical order)
Marcus Aguilar
Annette Guiseppi-Elie
Edward Ohanian
Region 9
Office of Research and
Development
Office of Water
Daniel Axelrad
Maureen Gwinn
Kathleen Raffaele
Office of Policy
Office of Research and
Office of Land and Emergency
Development
Management
Tina Bahadori
Intaek Hahn
Santhini Ramasamy
Office of Research and
Office of Research and
Office of Water
Development
Development
Kim Bartels
Ronald Hines
John M.Rogers
Region 8
Office of Research and
Office of Research and
Development
Development
Wayne Cascio
Kristen Keteles
Jason Sacks
Office of Research and
Region 8
Office of Research and
Development
Development
Elaine Cohen Hubal
Thomas Knudsen
LaTonya Sanders
Office of Research and
Office of Research and
Region 7
Development
Development
John Cowden
Nica Louie
Gretchen Stewart
Office of Research and
Office of Research and
Region 10
Development
Development
Michael Firestone
Mark Maddaloni
Maryann Suero
Office of Children's Health
Region 2
Region 5
Protection
Stiven Foster
Kelsey Maloney
Siobhan Tarver
Office of Land and Emergency
Office of Research and
Region 4
Management
Development
Andrew Geller
Jacquelyn Menghrajani
Prentiss Ward
Office of Research and
Region 9
Region 3
Development
Dayna Gibbons
Becky Ofrane
Benjamin Zukowski
Office of Research and
Region 2, U.S. EPA
Office of Research and
Development
Development
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Abbreviations and Acronyms
ACE
Air, Climate, Energy National Research Program
ADHD
Attention Deficit Hyperactivity Disorder
ATSDR
Agency for Toxic Substances and Disease Registry
BBDR
Biologically Based Dose Response
BPA
bisphenol A
CEH
children's environmental health
CEH IWG
Children's Environmental Health Implementation Working Group
CSS
Chemical Safety for Sustainability National Research Program
DDT
dichlorodiphenyltrichloroethane
EDSP
Endocrine Disruptor Screening Program
EPA
Environmental Protection Agency
FIFRA
Federal Insecticide, Fungicide, and Rodenticide Act
FY16
Fiscal Year 2016
HHRA
Human Health Risk Assessment National Research Program
HS
Homeland Security National Research Program
NHANES
National Health and Nutrition Examination Survey
NIEHS
National Institute of Environmental Health Sciences
NIH
National Institutes of Health
NRC
National Research Council
OCM
Organotypic Culture Models
OCSPP
Office of Chemical Safety and Pollution Prevention
OW
Office of Water
ORD
Office of Research and Development
PAH
Polycyclic Aromatic Hydrocarbon
PBDE
polybrominated diphenyl ethers
PCB
Polychlorinated biphenyl
PEHSU
Pediatric Environmental Health Specialty Unit
PFC
Perfluorinated Compound
SHC
Sustainable and Healthy Communities National Research Program
SmARTI
Smart Acceleration of Research Through Investment
SSWR
Safe and Sustainable Water Resources National Research Program
STAR
Science to Achieve Results
SVOC
Semivolatile Organic Compound
TSCA
Toxic Substances Control Act
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Executive Summary
Purpose of the Chill iviro in inn entail Health Research Roadmap
Protecting children's health from environmental risks remains a critical and enduring part of the U.S.
Environmental Protection Agency's (EPA's) mission. EPA conducts and supports children's environmental
health (CEH) research to inform regulatory decisions and to support community decision-making that
promotes sustainable, healthy environments for children. In October 2015, EPA's Office of Research and
Development (ORD) released the Children's Environmental Health (CEH) Research Roadmap, which
describes the Agency's strategic vision for CEH research. The CEH Research Roadmap provides EPA and
stakeholders with scientific understanding, information, and tools required to address early-lifestage
sensitivity, susceptibility, and vulnerability1 to chemical and nonchemical stressors.
The CEH Research Roadmap is not a research program. Rather, it integrates children's health research
activities across ORD's six Strategic Research Action Plans (https://www.epa.gov/research/strategic-
research-action-plans-2016-2019) developed by the ORD National Research Programs: Air, Climate, and
Energy (ACE); Chemical Safety for Sustainability (CSS); Human Health Risk Assessment (HHRA); Safe and
Sustainable Water Resources (SSWR); Sustainable and Healthy Communities (SHC), and Homeland
Security (HS). The CEH Research Roadmap describes crosscutting research needs that have two
important attributes: (1) they are "owned" by a National Research Program in a near-term timeframe;
and (2) they should enable EPA/ORD to take a transformative leadership role.
Purpose of the Ann port
This CEH Research Roadmap Annual Report summarizes progress made during the fiscal year on
research goals and activities described in the Research Roadmap; it also demonstrates EPA's
commitment to continue integrating and advancing this critical area of crosscutting research. This report
highlights successes and challenges of implementing ORD's CEH research during Fiscal Year 2016 (FY16;
October 1, 2015 to September 30, 2016). The report also identifies emerging issues or data needs that
could inform future research efforts.
"uiiiiii-r M II i'l«" CI H research Progress
ORD is investing heavily in CEH research—intramurally, extramurally, and through strategic
partnerships. Through each National Research Program research portfolio, ORD is collecting and
compiling data on children's exposures and providing access to information on exposure factors, human
1 Sensitivity- Differences in toxic response resulting from toxicodynamic differences, toxicokinetics differences, or both. These differences can
arise due to numerous biological factors such as lifestage (windows of enhanced sensitivity), genetic polymorphisms, gender, disease status,
and nutritional status.
Susceptibility - Differences in risk resulting from variation in both toxicity response (sensitivity) and exposure (due to gender, lifestage, and
behavior).
Vulnerability - Differences in risk resulting from the combination of both intrinsic differences in susceptibility and extrinsic social stress factors
such as low socioeconomic status, crime and violence, lack of community resources, crowding, access to healthcare, education, poverty,
segregation, and geography.
Lifestage - A distinguishable period in an individual's life characterized by unique and relatively stable behavioral or physiological (or both)
characteristics that are associated with development and growth.
Source: EPA/NCER 2013 RFA re: Susceptibility and Variability in Human Response to Chemical Exposure
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behavior, chemical use, and developmental toxicity. Complex systems models of tissues and multi-organ
development are being constructed, and studies are being implemented that combine epidemiological
and laboratory-based approaches, to provide a holistic understanding of the relationship between
early-life environmental exposures and well-being across the lifespan. ORD is developing tools and
models that can be used to access data, forecast exposures for thousands of chemicals, and evaluate
dosimetry of chemicals in the developing organism. ORD is also developing decision-support tools to
help States, local governments, and community organizations consider potential impacts of
environmental exposures in the context of decisions designed to protect and promote children's health.
Selected of FY16 research products are highlighted here. Complete references for FY16 peer-reviewed
publications and for the citations in the body of this report are presented in Appendix A.
In FY16, ORD CEH research resulted in the development of pharmacokinetic models of vasculogenesis
(El-Masri et al. 2016), computational models of estrogen receptor activity (Mansouri et al. 2016), and in
silico models of reproductive development (Leung et al. 2016a, 2016b). These predictive models are part
of a larger research effort on development health. ORD continued developing novel screening
approaches for developmental neurotoxicants in FY16 (Druwe et al. 2016). Research also furthered
progress on adverse outcome pathways for developmental neurotoxicity, including investigations on
epigenetic modifications (Perumal-Kuppusamy et al. 2015; Vidal et al. 2015) and the lasting impacts of
prenatal thyroid hormone disruption (Gilbert et al. 2016; Spring et al. 2016). A systematic scoping review
synthesized evidence of both chemical and nonchemical stressors, reporting prenatal growth, sleep
health, lead, water pollutants, breastfeeding, and social interactions as factors associated with
childhood cognitive ability (Ruiz et al. 2016). Consideration of both chemical and nonchemical stressors,
organized by common adverse outcomes and biological targets, is a first step towards understanding the
cumulative impact of the environment on the developing nervous system (e.g., Kraft et al. 2016).
ORD's systems approach to hazard and exposure integrates a variety of data streams (e.g., in vitro, in
vivo, and in silico) to inform complex risk decisions, such as lead contamination in drinking water. Risk
decisions require understanding both hazard and exposure. In FY16, ORD researchers developed
methods to directly measure chemical exposure in children (Funk et al. 2015) and built predictive
exposure models for perfluorinated compounds (Wu et al. 2015a) and polybrominated diphenyl ethers
(Bennett et al. 2015; Wu et al. 2015b; Marchitti et al. 2016).
A fundamental challenge for EPA is evaluating the combined impact of chemical (e.g., Howdeshell et al.
2015; Moser et al. 2015; Paul Friedman et al. 2016) and nonchemical (e.g., Chen et al. 2015; Morgan et
al. 2015; Vesper et al. 2015; Arnold et al. 2016; King et al. 2016; Vesper and Wymer 2016) stressors on
children's health. ORD's FY16 work demonstrates that coordinated and focused research can provide
rapid response to emerging issues of concern, such as indoor air quality. The systems approach outlined
in the CEH Research Roadmap, and integrated into ORD's research portfolio, is the first step in
characterizing cumulative impacts of the built, natural, and social environments on children's health.
In FY16, EPA and NIEHS awarded five new NIEHS/EPA Children's Center grants. Research supported
under these awards includes the interplay of particulate matter and obesity on asthma among inner city
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children; prenatal and early childhood pollutant exposure and adverse birth outcomes; polycyclic
aromatic hydrocarbons and adolescent cognitive, emotional, behavioral health outcomes; cumulative
environmental exposures and increased risk for childhood acute lymphoblastic leukemia; and the effects
of environmental contaminants on the microbiome and neurodevelopment.
Suiiriiiiri ii -if I i I' CI.III Psearch Translation
To protect vulnerable lifestages, ORD collaborates with partners and stakeholders to CEH research can
be translated into action. In FY16, ORD regularly communicated CEH research at scientific meetings and
conferences in the United States and abroad as well as targeted meetings and presentations for ORD
partners in Programs and Regions. For instance, ORD researchers partnered with the Endocrine
Disruptor Screening Program (EDSP) to develop and evaluate a high-throughput screening assay with
over 1,000 chemicals from the ToxCast Phase I and II libraries (Paul Friedman et al. 2016). This work is
part of a larger collaborative ORD research effort to develop in vitro high-throughput assays and
computational models for detecting receptor activity in endocrine pathways, including androgen and
thyroid.
Another effort to translate ORD CEH research is through support to the Zika Interagency Task Force, a
cross-Federal government partnership established to address the emerging health issue from the Zika
virus. Laboratory studies are underway within ORD, Organotypic Cell Model Science to Achieve Results
(STAR) Centers, and other external collaborations to probe maternal viral infection and develop a virtual
tissue model for microcephaly. ORD CEH research also is informing the Presidential mandate to
investigate potential risk to children from exposure to tire crumbs. In FY16, Synthetic Turf Fields with
Tire Crumb Rubber Infill Research Protocol was drafted to provide a standard method to evaluate the
chemical make-up of tire crumbs. ORD scientists are gathering tire crumb samples from manufacturing
plants and fields across the country and will release a draft status report in late 2016.
ORD scientists are providing technical assistance to address the issue of lead in drinking water. In FY16,
exposure and dose model predictions, generated with the Stochastic Human Exposure and Dose
Simulation-Multimedia and Integrated Exposure Update Biokinetic models, were used to identify key
exposure pathways and model inputs, providing health-based values for evaluating lead in drinking
water. In another important effort focusing on exposure and dose, ORD developed a novel
physiologically based pharmacokinetic approach to inform the derivation of the maximum contaminant
level goal for perchlorate in drinking water. This unprecedented effort uses a biologically based dose-
response (BBDR) model to estimate the effects of perchlorate exposure on hormone levels in pregnant
mothers and fetuses.
Internally, ORD has built a coalition of children's health experts through the CEH Implementation
Working Group (IWG). The CEH IWG, whose members are listed at the beginning of this report, is
composed of ORD researchers, ORD National Research Program leadership, and EPA Program Office and
Regional partners. The group meets monthly to learn about and help translate results of CEH research,
facilitate integration, and leverage ongoing efforts to implement the strategic vision of the CEH Research
Roadmap.
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Sun eairch Impact
In FY16, ORD CEH research substantially contributed to multiple, high-profile Agency efforts. Risk
decisions about perchlorate in drinking water and pesticide applicator certifications relied on ORD
research to protect vulnerable lifestages. ORD's research on lead was the scientific foundation for EPA's
response to drinking water contamination in Flint, Michigan. ORD CEH research provided critical
biological context for microcephaly following exposure to Zika virus, and informed EPA's
recommendations for combating mosquito vectors. ORD research on endocrine disruptors, including
screening compounds and building predictive models, continued to provide critical support to the EDSP.
These activities clearly demonstrate that ORD CEH research directly supports the efforts of EPA's Science
Advisor and are essential for protecting children's health.
II ii >';ires. -iik! II merging Opportunities
FY16 was the first full year the CEH Research Roadmap was implemented. ORD scientists produced an
impressive number of peer-reviewed publications (Appendix A), continuing EPA's legacy of scientific
leadership in CEH research. ORD CEH research and scientific expertise were applied to critical Agency
needs (e.g., contaminated drinking water, tire crumbs, Zika virus, endocrine disruption) through
collaborations with partners and stakeholders. Because of these science translation efforts, ORD
research was the cornerstone for EPA risk decisions on pesticide application, perchlorate, and lead.
Looking ahead, the focus will remain on translating ORD's research to support EPA's public health
mission. Future research will apply complex systems science to integrate the rapidly expanding body of
information on children's health. This information will be translated into tools and databases to support
Agency decisions that promote and protect children's health and well-being. ORD will apply advanced
systems science and integrate diverse emerging data and knowledge in exposure, toxicology, and
epidemiology to improve understanding of the role of environmental exposure during early life on
health impacts that could occur at any point over the lifecourse.
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I. Accomplishments
This section describes the Office of Research and Development's (ORD) efforts to integrate, coordinate,
and deliver children's environmental health (CEH) research products and to support several high-priority
issues across the U.S. Environmental Protection Agency (EPA) in FY16. In addition to peer-reviewed
publications, results of ORD research are regularly communicated through scientific meetings and
conferences in the United States and internationally, and at targeted meetings and presentations for
ORD partners in EPA Program Offices and Regions. ORD also regularly collaborates with these partners
to translate its research for use in EPA actions and decisions, including risk assessments and health
advisories. Example impacts of ORD CEH research on EPA decisions are provided. "Research Highlights"
boxes showcase a sample of impactful publications, and several research projects are described in the
section, Integration of CEH Research for Impact Delivery, to demonstrate progress toward integrating
this research among the National Research Programs. Appendix A provides a complete list of ORD CEH
peer-reviewed manuscripts delivered during the fiscal year.
A. Impacts of ORD CEH Research on EPA Decisions
In FY16, results from ORD's
intramural and extramural CEH
research were used to inform
several pesticide risk
assessments and EPA's decisions
regarding safe drinking water,
contaminants of emerging
concern, dietary exposures, and
air pollution health. Critical CEH
issues addressed by ORD
research included certification of
pesticide applicators, screening
for endocrine disrupting
compounds, microcephaly from
Zika virus, analysis of exposure
effects of tire crumbs, and
recommendations for
remediating lead contamination
in drinking water. These
activities directly support the
efforts of EPA's Science Advisor
and are essential for protecting
children's environmental health.
Research Highlight
Exposure to elemental carbon, organic carbon, nitrate, and sulfate
fractions of fine particulate matter and risk of preterm birth in New
Jersey, Ohio, and Pennsylvania (2000 2005). Rappazzo et aI.;
Environmental Health Perspectives 2015 Oct; 123(10):1059 65. doi:
10.1289/ehp. 1408953.
Exposure to particulate matter < 2.5 p.m (PM2.5) during pregnancy is
associated with preterm birth. There are numerous PM2.5 species, but
few studies have examined how the different species contribute to risk
of preterm birth. Risk of preterm birth associated with prenatal exposure
to changes in ambient concentrations of PM2.5—specifically elemental
carbon, organic carbon, nitrate, and sulfate—was the focus of this
manuscript.
Using a cohort of approximately 1.8 million pregnancies, the study
identified associations between average weekly PM2.5 exposure during
gestation and risk of preterm birth. The study reported differences
among PM2.5 species, with elemental carbon and sulfate showing
consistent association with risk for preterm birth. Differences in windows
of exposure and risk of preterm birth at specific gestational ages were
also reported for the PM2.5 species. These results suggest diverse
periods of action for the PM2.5 species ofPM, along with differing
windows of susceptibility.
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Certification of Pesticide Applicators
Research from the jointly funded EPA/National Institute of Environmental Health Sciences (NIEHS)
Children's Environmental Health and Disease Prevention Research Centers (Children's Centers) informed
the proposed Certification of Pesticide Applicators rule revision in FY16. EPA is proposing age restrictions
and stronger training and certification standards for restricted-use pesticides. EPA risk decisions and
data from the Children's Centers were cited in the July 2016 Economic Analysis of Final Amendments to
40 CFR part 171: Certification of Pesticide Applicators. In addition, the Scientific Advisory Panel for the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) used data generated by the Children's
Centers in their review of biomonitoring and epidemiological data for chlorpyrifos
(https://www.epa.eov/sap/meetine-materials-aDril-19-21-2016-scientific-advisorv-panel).
Organophosphates- Retention of Safety Factor
In October 2015, EPA's Office of Chemical Safety and Pollution Prevention (OCSPP) proposed to revoke
all food residue tolerances for the insecticide, chlorpyrifos. The proposed rule retained the statutory 10X
Food Quality Protection Act Safety Factor for infants, children, youths, and women of childbearing age
for all exposure scenarios (https://www.federalreeister.eov/documents/2015/ll/06/2015-
28083/chlorpvrifos-tolerance-revocations). The rule included data from three Children's Centers: the
Columbia Center for Children's Environmental Health, the Mount Sinai Center for Children's
Environmental Health and Disease Prevention Research, and the Center for Environmental Research and
Children's Health. The review of "Chlorpyrifos - Analysis of Biomonitoring Data" and inclusion of
epidemiological data continues as discussed by the 2016 FIFRA Scientific Advisory Panel
(https://www.epa.eov/sap/meetine-materials-april-19-21-2016-scientific-advisorv-panel).
Endocrine Disrupter Screening Program (EDSP)
In FY15, EPA announced its plans to adopt in vitro high-throughput assays and computational models for
detecting and measuring estrogen receptor bioactivity as an alternative for three current assays in the
EDSP (http://www.epa.eov/endocrine-disruption/use-hieh-throuehput-assays-and-computational-tools-
endocrine-disruptor). This "pivot," which will be expanded to other endocrine pathways including
androgen and thyroid, was driven largely by ORD's advances in computational toxicology research and
successful collaborations with NIEHS. For the androgen pathway, the FY16 focused on approaches to
validate high-throughput assays and computational predictive model as a potential alternative for
traditional EDSP screens. For the thyroid pathway, significant emphasis was placed on expanding the
assay portfolio in ToxCast (https://actor.epa.eov/actor/home.xhtml). For example, ORD researchers
developed and tested a high-throughput screening assay and used over 1,000 chemicals in the ToxCast
Phase I and II libraries to evaluate its performance further (Paul Friedman et al. 2016). The plan to
incorporate these new approaches into the EDSP will be reviewed at upcoming meetings of the FIFRA
Science Advisory Panel.
Microcephaly and Zika Virus
Infection from the Zika virus has been associated with devastating effects on prenatal neurological
development, including microcephaly and optical or aural anomalies. The Zika virus is spread by the
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Aedes aegypti mosquito, and EPA has endorsed an integrated vector management approach for
mosquito control. ORD collaborates with EPA Program Office partners and other Federal partners to
support the Zika Interagency Task Force. ORD has developed research priorities for the task force and
initiated projects to address some of the identified environmental and public health research gaps. A
research effort in Brownsville, Texas is gathering spatial and temporal information on Aedes aegypti
distribution in relation to habitat and developing models to forecast future vulnerabilities to Zika and
other mosquito-borne diseases. A project in San Juan, Puerto Rico is investigating potential relationships
between wastewater discharge, flooding, and habitat alteration to mosquito population size, viral load,
and infections of nearby residents. Laboratory studies are underway to develop a virtual tissue model
for microcephaly to understand its various causes, including Zika infection. ORD researchers have
collaborated with investigators from two of the Organotypic Cell Model STAR Centers to probe maternal
infection and Zika mode of action and have provided a foundation for additional research. ORD will
continue to work closely with Federal partners to identify and address emerging research needs for this
growing threat.
Recycled Tire Crumbs and Health Risks
Use of recycled tire crumbs in playing fields and playgrounds in the United States has recently raised
public safety concerns, and no available studies comprehensively evaluate health risks from exposure to
tire crumb. To address these concerns, EPA, the Centers for Disease Control and Prevention/Agency for
Toxic Substances and Disease Registry (ATSDR), and the U.S. Consumer Product Safety Commission
launched the United States Federal Research Action Plan on Recycled Tire Crumb Used on Playing Fields
on February 12, 2016 to study key environmental human health questions. The Synthetic Turf Fields with
Tire Crumb Rubber Infill Research Protocol provides an overview of the peer-review study design for this
research. ORD scientists are collecting tire crumb samples from manufacturing plants and from fields
across the country to characterize their chemical make-up. Scientists also will gather activity data from
people who regularly perform activities on turf fields. This information will help answer some of the key
questions that have been raised. By late 2016, the agencies will release a draft status report and outline
next steps. For more information about the research, visit the Tire Crumb Research
website: www.epa.gov/tirecrumb.
Remediating Lead Contamination in Drinking Water
EPA's Office of Water (OW) requested technical assistance on the Lead and Copper rule, and ORD
scientists are responding by conducting multimedia exposure analyses to inform a public health-based
value for lead in drinking water. Using a probabilistic modeling methodology and multimedia lead
exposure analysis, they are determining drinking water lead levels that would keep children's blood lead
level below target concentrations. As part of this analysis, the exposure and dose model predictions
from the coupled Stochastic Human Exposure and Dose Simulation-Multimedia and Integrated Exposure
Update Biokinetic models have been evaluated using National Health and Nutrition Examination Survey
(NHANES) blood lead data to identify key exposure pathways and model inputs. The final analyses will
support the development of a health-based value for lead in drinking water.
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Perchlorate Dose-Response Modeling
In response to OW's request for technical support on the perchlorate National Primary Drinking Water
Regulation, ORD scientists developed a BBDR model to estimate the effect of perchlorate exposure on
serum thyroid hormone levels in pregnant mothers and fetuses. The BBDR model predicts thyroid
hormone perturbations for lactating mothers, breast-fed infants, and bottle-fed infants resulting from
exposure to perchlorate under different intake levels of dietary iodine. The modeling effort is being used
to inform the regulatory decisions for perchlorate levels in drinking water. This effort represents the first
time that OW will have relied on information that characterizes specific effects on multiple, early
lifestages to inform a drinking water regulation.
IB, Integration of CEH Research for Impact Delivery
The CEH Research Roadmap outlines integrative research across ORD National Research Programs. In
FY16, ORD began implementing CEH Roadmap recommendations through several cross-disciplinary
research projects. These projects leverage ORD scientists, EPA Program Office partners, and academic
researchers to provide EPA with fundamental research on children's environmental health. Highlights of
these projects are provided below.
Virtual Tissues Modeling Research Project - Integrating EPA's Intramural and Extramural Research
Understanding the impact of chemical exposures on the developing embryo is critical to CEH research.
The Virtual Tissue Modeling Research Project uses in vitro and in vivo data to build in silico models of
human development. These computer simulation models promote systems-level understanding of
chemical exposures that could lead to adverse outcomes in development. Ultimately, the in silico
models could serve as an analytical tool for predicting effects of chemical exposure on embryogenesis.
The project is a collaboration with EPA-funded Science to Achieve Results (STAR) grantees of the
Organotypic Culture Models (OCMs) for Predictive Toxicology Centers (OCM Centers; see Table 3). OCM
Center researchers participate in project meetings, allowing for real-time flow of science and knowledge
and for EPA to incorporate "organ-on-a-chip" research models into EPA's predictive toxicology research
and activities.
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An example of this integration is the collaborative development of novel models for EPA's
developmental neurovascular toxicology research. Although EPA research has had a notable focus on
the thyroid, this engagement with academic and biotechnology partners has significantly accelerated
EPA's learning curve: This transfer of technology and knowledge is at least 3 to 4 years ahead of
expectations. EPA was able to
reprioritize and redirect
intramural resources to support
the neurovascular OCM and its
research team. Conversely,
engagement with EPA has helped
the OCM grantees direct the case
studies in their research toward
topics that would have relevance
to EPA's public and
environmental health protection
mission. Several new
postdoctoral students are being
recruited to advance this effort.
Developmental Health -
Integrating across ORD and
with Program and Regional
Partners
EPA implements screening,
testing, and research programs to gather information for use in evaluating possible endocrine effects
associated with chemical use (https://www.epa.gov/endocrine-disruption). The EDSP's chemical
screening list contains approximately 10,000 chemicals. The FY15 announcement to incorporate high-
throughput technologies to accelerate the pace of EDSP screening, described above, signaled an
imminent opportunity to demonstrate the relevance and potential applicability of ORD CEH research to
environmental policy in near real time.
Taking advantage of this opportunity and policy focus, ORD also increased its research focus on
developmental health, vulnerable lifestages, and susceptible populations. This research supports
progress in understanding adverse outcome pathways (AOPs) associated with important developmental
health processes and those associated with disease endpoints of concern. Mechanistic toxicology
information and epidemiology insights are being assembled within CSS, SHC, and ACE National Research
Programs to facilitate model development and analysis of critical knowledge gaps. In FY16, ORD
published novel screening approaches for developmental neurotoxicants (Druwe et al. 2016). Research
also progressed on AOPs for developmental neurotoxicity, including investigations on epigenetic
modifications (Perumal-Kuppusamy et al. 2015; Vidal et al. 2015) and the persistent impacts of prenatal
thyroid hormone disruption (Gilbert et al. 2016; Spring et al. 2016). Computational models of estrogen
receptor activity (Mansouri et al. 2016) and in silico models of reproductive development (Leung et al.
Research Highlight
Integration of life stage physiologically based pharmacokinetic (PBPK)
models with adverse outcome pathways (AOPs) and environmental
exposure models to screen for environmental hazards. El Masri et al.;
Toxicological Science (2016) doi: 10.1093/toxsci/kfw082.
Physiologically based pharmacokinetic (PBPK) models describe what the
body does to a chemical and how chemicals are absorbed, distributed,
metabolized, and excreted. Because developing fetuses and infants are
especially sensitive to chemical exposure, a PBPK model was developed
to describe where chemicals end up based on various lifestages:
pregnancy, fetal, neonatal, infant, and adulthood.
EPA scientists integrated the lifestage-specific PBPK model with existing
data on in vitro high-throughput screening assays using an adverse
outcome pathway on embryonic vascular disruption. The universal
model takes into consideration important biologically relevant factors
and real-life chemical exposure levels to create a framework applicable
to chemicals of interest for children's environmental health. This
framework can be used to screen and prioritize chemicals for further
research or regulatory decision-making.
5
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2016a, 2016b) also have informed this research focus. A systematic scoping review synthesized evidence
of both chemical and nonchemical stressors, reporting prenatal growth, sleep health, lead, water
pollutants, breastfeeding, and social interactions as factors associated with childhood cognitive ability
(Ruiz et al. 2016). Consideration of both chemical and nonchemical stressors, organized by common
adverse outcomes and biological targets, is a first step toward understanding the cumulative impact of
the environment on the developing nervous system (e.g., Kraft et al. 2016).
Safe Drinking Water-The Lead Example: Integrating across Policy Domains
ORD supports Agency efforts to reduce childhood exposure to lead and characterize associated health
impacts through innovative research in SSWR, SHC, and HHRA National Research Programs. ORD
research focuses on understanding and characterizing population-level exposures to lead from multiple
sources such as soil, dust, and water; furthering the scientific understanding of human health effects of
lead exposures, especially on sensitive lifestages; and advancing the science on how best to mitigate
lead exposure from different
environmental sources. Projects
include evaluating water
chemistry adjustments to control
the leaching of lead from pipes,
analyzing lead bioavailability and
risk from exposure to lead in soil,
and developing improved
approaches for remediating lead-
contaminated soils. Other areas
include drinking water
technology research to address
the unique needs of small
communities in preventing lead
contamination of drinking water
and community case studies that
evaluate the socioeconomic impacts of lead contamination at a large urban Superfund site. ORD's 2013
Integrated Science Assessment for Lead is being updated by synthesizing and evaluating the most policy-
relevant science in support of National Ambient Air Quality Standards for lead.
Indoor Air and Health - Emerging Area of Integration
An emerging area of research interest among ORD's National Research Programs is indoor air and
health, including indoor air and climate (ACE), healthy schools and science to support healthy Tribal
environments (SHC), indoor exposures to consumer products (CSS), and the microbiome of built
environments (across ORD and with EPA's Office of Radiation and Indoor Air). Components of this
research area are addressed through new STAR grants (see Table 4) and intramural research in the
National Research Programs. One crosscutting element focuses on nontargeted analyses, based on high-
Research Highlight
The relationship between environmental relative moldiness index
values and asthma. Vesper & Wvmer. International Journal of Hvaiene
and Environmental Health (2016). doi: 10.1016/i.iiheh.2016.01.006.
Mold exposure is qualitatively associated with asthma, but efforts to
quantify this relationship have been limited. To address this issue
quantitatively, the relationship between asthma and a measure of
indoor mold was analyzed. The environmental relative moldiness index
(ERMI) value, derived from analysis of molds in dust samples, was
compared with asthma incidence data from six epidemiological studies
in both children and adults. The results show children and adults with
asthma were living in homes with significantly higher ERMI values than
comparison homes. Based on this study, the ERMI metric could be a
useful public health tool to mitigate a factor associated with higher
asthma incidences.
6
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resolution mass spectrometry platforms, to screen for xenobiotic chemicals in a variety of
environmental and biological media and to use these approaches to inform real-world exposures.
clh to Partners and Stakeholders
This section highlights the interaction between ORD and EPA partners in Program and Regional Offices
and ORD and public stakeholders. Such interaction is essential for integrating ORD scientific research
into relevant decision contexts and ensuring relevance of ORD research products for users. This section
also presents successes in addressing programmatic recommendations from scientific advisory groups.
Scientific and Advisory Bodies
EPA's Science Advisory Board and the Executive Committee of its Board of Scientific Counselors have
provided guidance on the development of the CEH Research Roadmap. The Board will continue to
monitor progress on the implementation, integration, and impact of EPA's CEH research.
In addition, EPA has commissioned the National Academies of Sciences, Engineering, and Medicine to
evaluate the state of the-science and recommend approaches for using emerging science to promote
effective, health-protective decisions and actions. Several of these studies will inform ORD's CEH
research efforts. Examples of formative studies follow.
Unraveling Low Dose: Case Studies of Systematic Review of Evidence (In progress)
An ad hoc committee under the auspices of the National Research Council (NRC) is developing a strategy
for evaluating evidence of low-dose adverse human effects that act through an endocrine-mediated
pathway. Systematic reviews of chemicals, populations, and endpoints for human and animal data
streams will be performed under the direction of the committee. The committee will evaluate the
results of the systematic reviews, demonstrate how human and animal data streams can be integrated,
determine whether the evidence supports a likely causal association, and evaluate the nature and
relevance of the dose-response relationship(s). The results of the committee's evaluation of low-dose
toxicity can be used to inform EPA on the adequacy of its current regulatory toxicity-testing practices. A
consensus report is expected in early 2017.
Microbiome of Built Environments
The National Academies of Sciences, Engineering, and Medicine are conducting a consensus study that
will examine the formation and function of microbial communities in built environments, the impacts of
such microbial communities on human health, and how human occupants shape complex indoor
microbiomes. This study is intended to provide an independent, objective examination of the current
state of science regarding built environment microbiomes and their impacts on human health. Attempts
then will be made to bridge gaps in moving this research to an application stage, in which building
materials and architecture will be designed with microbiomes in mind. The consensus report for the
study, which is being conducted by a committee of experts, is expected in 2017.
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Advancing Understanding of the Implications of Environmental-Chemical Interactions with
Human Microbiomes
An ad hoc committee of the NRC will develop a research strategy to improve the understanding of
interactions between environmental chemicals and human microbiomes, including the intestinal, skin,
and lung microbiomes, and the implications of those interactions on human health risk. The committee
will assess the state of science regarding how the microbiome affects, and is affected by, chemical
exposures. It will also assess how lifestage or interindividual differences in microbiota, for example,
might influence effects. The research strategy will identify the types of studies needed to improve
understanding of how various microbiome communities can affect chemical absorption and metabolism,
how population variation in microbiome activity might affect individual chemical exposure, and the
effect of chemical exposure on microbiome functions and possible implications for human health risk. A
consensus report is expected in 2018.
Program Offices and Regions
ORD's CEH research is implemented through the CEH Research Roadmap. A Children's Environmental
Health Implementation Working Group (CEH IWG) was established in FY16 to facilitate cross-ORD
implementation of the CEH Research Roadmap; enhance communication about CEH research among
ORD researchers, partners, and stakeholders; and serve as a resource for EPA leadership on CEH
research and science. The CEH IWG provides a forum for communication and collaboration among EPA
Program Offices, Regional Offices, and ORD's National Research Programs. The group meets monthly to
discuss CEH issues of priority for EPA and progress in ongoing research, creating early and frequent
opportunities for engagement, translation, and collaboration.
EPA and ATSDR co-fund Pediatric Environmental Health Specialty Units (PEHSUs;
http://www.pehsu.net/). an interconnected system of pediatric medical specialists located throughout
North America. The PEHSU network supports translation from healthcare research to practice. These
pediatric specialists respond to questions about the impacts of environmental factors on the health of
children and reproductive-age adults from public health professionals, clinicians, policy-makers, and the
public. The PEHSUs, located in each of EPA's 10 Regions, operate under the umbrella of the American
Academy of Pediatrics and the American College of Medical Toxicology.
PEHSUs also partner with the EPA/NIEHS Children's Centers and EPA Regions.
Efforts to have the PEHSUs partner with the NIEHS/EPA Children's Centers
have increased. Examples include the Story of Health, an award-winning
multimedia e-book on environment and health created in collaboration
between the Region 9 PEHSU and the University of California - Berkeley
Children's Center. In Region 7, the PEHSU program partnered with the Center
for Environmental Health at Children's Mercy, a hospital in Kansas City,
Missouri, to provide education, consultation, and referrals for children with
environmental exposures. Additionally, the Center for Environmental Health
has successfully delivered Healthy Homes and Healthy schools training
throughout the Region: More than 700 healthcare students and 275 healthcare professionals have been
A Story
of Health
8
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educated to advocate for home-based environmental changes that can improve children's health. The
Center for Environmental Health-PEHSU effort will present 10 more Healthy School trainings and
provide at least 2 more training courses to local Tribal communities during FY17 and FY18.
Current List of Products/Peer-Reviewed Publications
In FY16, ORD CEH research resulted in more than 290 abstracts, book chapters, peer-reviewed
publications, posters, and presentations. A table of the completed ORD CEH research manuscripts is
provided in Appendix A. The list represents ORD's FY16 manuscripts related to CEH that have been
accepted by journals for publications. This table presents products of intramural research only.
Numerous publications from extramural grants, including STAR Grants, Children's Centers, and others
are tracked by the STAR program and reported publicly as required by that program. To facilitate review,
the articles in Appendix A are loosely organized by research areas, such as exposure evaluation, or
health outcomes, such as asthma, that were identified as high priority in the CEH Research Roadmap.
Much of the research, which is crosscutting and transdisciplinary by design, could fall into multiple
categories. In addition, articles that are also relevant to an emerging research area—early-life
determinants of cancer, the microbiome, thyroid disruption—are listed.
ID, Encouraging Innovation
ORD has established a variety of mechanisms to germinate, encourage, and support innovation in
science research projects. This section describes ORD's commitment to advancing innovation in CEH
research within ORD and through its extramural grants.
Pathfinder Innovation Projects
The Pathfinder Innovation Projects (PIPs) program is the "high risk, high reward" component of ORD's
research portfolio. PIPs foster development of transformative ideas through a competitive renewal
process, with funding awards progressively increasing at each stage. At the final stage of the
competition, these innovation projects are incorporated into ORD's strategic research action plans.
Stage 1. Explore your Idea: Applicants propose short-term projects (<4 months, <$30 K, <0.5 FTE
[full-time equivalent]). The primary resource provided to awardees is time to test an idea's viability,
better understand the technical challenges, and scope future work.
Stage 2. Prove your Concept: At the end of the exploration period, Stage 1 awardees propose
longer-term projects (<12 months, <$100 K, <1.5 FTE). Funding is used for proof-of-concept, limited
demonstration, or scale-up of the project.
Stage 3. Scale Up your Project: Concurrent with Stage 2 review, Stage 2 awardees propose long-
term efforts (>12 months, <$250K, <1.5 FTE) to expand on their PIP research to date. Researchers
must have successfully demonstrated proof-of-concept and have a well-articulated plan to expand
the work with NPD support.
Table 1 provides a synopsis of FY16 PIPs related to goals outlined in the CEH Research Roadmap.
9
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Table 1. Pathfinder Innovation Projects (PIPs)
Title
Brief Description
PIP
Stage
Development of a novel method to
estimate children's dust ingestion
Identify candidate compounds that can be used as potential
tracers to estimate children's dust ingestion rates using a
systematic framework.
Stage 1
Fetal origins of lifestage disease
Develop an embryonic zebrafish model to test whether
manufactured chemicals (1) disrupt normal control over fat-cell
development and (2) influence fat volume later in life.
Stage 1
Gut microbiome influence on
developmental toxicity
Develop multiple zebrafish assays to test whether microbial
colonization modifies the developmental toxicity of
environmental chemicals.
Stage 2
Use of epigenetic information to
transform how EPA identifies
susceptible populations
Develop methods to examine and characterize impact air
pollutants on chromatin and gene expression for insights on
susceptibility.
Stage 2
The "brain on a chip" model for
developmental neurotoxicity testing
Develop a rapid method to screen chemicals for developmental
neurotoxicity by examining the responses of neuron networks.
Stage 3
Smart Acceleration of Research Through Investment Awards
The FY16 Smart Acceleration in Research Through Investment (SmARTI) Awards provided an opportunity
for research proposals supporting strategic collaborations or ideas ready for implementation. Of the
three SmARTI Awards funded, two were CEH-relevant:
1. Identification of potential thyroid hormone-disrupting chemicals that interfere with
deiodinase enzymes: Develop screening assays for deiodinase enzymes responsible for
activation and catabolism of thyroid hormones.
2. A high-throughput examination of the universe of chemicals that might appear in a variety of
recycled consumer articles to identify, quantify, and prioritize potential chemical exposure
sources in recycled materials (e.g., tire-derived rubber): Examine the universe of chemicals that
might appear in various recycled consumer articles in an innovative, high-throughput manner, in
support of identifying, quantifying, and prioritizing potential chemical exposure sources.
Science to Achieve Results (STAR) Grants
The National Center for Environmental Research's STAR program funds research grants and graduate
fellowships through a competitive solicitation process and independent peer review. The leading edge
of CEH science is driven through transformative research conducted in academia through the STAR
program. The centerpiece of this investment is the NIEHS/EPA Children's Environmental Health and
Disease Prevention Research Centers (Children's Centers) primarily funded by the SHC research
program, which are described in more detail below and in Table 2. Table 3 lists the previously funded
NIEHS/EPA Children's Centers that closed in FY16. In addition, over a dozen other STAR grants funded by
10
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the National Research Programs, summarized in Table 4, investigate key issues related to CEH, including
exposure to complex mixtures, modeling of developmental health, indoor environments, and Tribal
health.
Children's Environmental Health and Disease Prevention Research Centers
The Children's Centers were established to improve understanding of the effects of exposure to
chemical and nonchemical stressors on children's health and to explore ways to reduce children's health
risks from environmental stressors. Additionally, the Children's Centers promote translation of basic
research findings into intervention and prevention methods to prevent or reduce adverse health
outcomes.
Table 2 lists the currently funded Children's Centers. Many of these Centers have received funding as
part of the Children's Centers program. In FY16, NIEHSand EPA jointly funded five new Centers
(italicized below). The Children's Centers publish extensively on the results of their research. For more
information about each Center, visit the EPA Children's Centers homepage:
https://www.epa.gov/research-grants/niehsepa-childrens-environmental-health-and-disease-
prevention-research-centers.
Table 2. NIEHS/EPA Children's Environmental Health and Disease Prevention Research Centers
Center Name
Year
Funded
Institution
Research Goals
Center for the Study of Childhood
Asthma in the Urban Environment
https://cds.iohnshopkins.edu/cei/
index.cfm?fuseaction=dispiav pr
oaram&id=114
2015
Johns
Hopkins
University
Explore how exposure to air pollution causes
high rates of asthma in the inner city. Define the
relationship between obesity, asthma, and air
pollution in inner city African-American
children.
Center for Children's Health, the
Environment, the Microbiome,
and Metabolomics
http://www. n ursin a. emorv. edu/c
-chem2/index.html
2015
Emory
University
Characterize environmental exposures to
African-American women during pregnancy and
to their infants. Explore how environmental
exposures during pregnancy and infancy, the
microbiome, and the immune system work
together to influence brain development.
The Columbia Center for
Children's Environmental Health
http://ccceh. or a/
2015
Columbia
University
Define the effects of air pollution, specifically
polyaromatic hydrocarbons, on brain
development, obesity, and inability to regulate
thought, emotion, and behavior. Investigate if
these changes in brain development can lead to
serious cognitive, emotional, and adiposity
problems during adolescence.
Center for Research on Early
Childhood Exposure and
Development in Puerto Rico
http://www.northeastern.edu/cre
ce/
2015
Northeastern
University
Study the effects of chemical mixtures on child
health and development. Focus on an
underserved, highly exposed, low-income
population in Puerto Rico. Evaluate how social
and economic factors could modify the effects
of the environment on children's health.
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Table 2. NIEHS/EPA Children's Environmental Health and Disease Prevention Research Centers
Center Name
Year
Funded
Institution
Research Goals
Center for Integrative Research
on Childhood Leukemia and the
Environment
http://circle. berkelev. edu/
2015
University of
California,
Berkeley
Identify the causes of acute lymphoblastic
leukemia in an ethnically diverse population.
Understand how environmental factors increase
risk of acute lymphoblastic leukemia.
UC Davis Center for Children's
Environmental Health and
Disease Prevention
httD://www. ucdmc.ucdavis.edu/
mindinstitute/research/cceh/ind
ex.html
2013
University of
California,
Davis
Identify risk factors contributing to autism
spectrum disorder. Understand early markers of
risk to identify children who might develop this
disorder.
The UCSF Pregnancy Exposures to
Environmental Chemicals
Children's Center
httD://Drhe. ucsf.edu/Drhe/PE EC
childrens center.html
2013
University of
California,
San Francisco
Determine the impacts of in utero exposure to
hazardous chemicals, such as polybrominated
diphenyl ethers (PBDEs) and perfluorinated
compounds (PFCs), on child growth and
development. Evaluate how social stress on the
mother during pregnancy might modify the
effects of these chemicals on children's health.
Novel Methods to Assess Effects
of Chemicals on Child
Development
http://ikids.beckman. illinois.edu/
2013
University of
Illinois
Examine the impact of endocrine disrupting
chemicals, such as bisphenol A (BPA) and
phthalates, on child development. Investigate
how these chemicals interact with diets high in
saturated fat to influence brain and
reproductive system development.
Children's Health and Air
Pollution Study - San Joaquin
Valley
httD://cha Ds.berkelev.edu/
2013
University of
California,
Berkeley;
Stanford
University
Investigate how air pollution in the San Joaquin
Valley contributes to birth defects, preterm
birth, allergies, obesity, diabetes, and other
childhood illnesses. Evaluate the role of social
and economic factors on the health effects
associated with air pollution.
Lifecourse Exposures and Diet:
Epigenetics, Maturation, and
Metabolic Syndrome
https://sph. umich.edu/cehc/inde
x.html
2013
University of
Michigan
Understand how early exposure to endocrine
disrupting chemicals, such as BPA, lead, and
phthalates, produce adverse
neurodevelopmental, reproductive, and
immunological effects. Explore how early
exposure to these chemicals affects growth and
sexual development during childhood and
adolescence to increase risk of disease in
adulthood.
Center for Study of
Neurodevelopment and
Improving Children's Health
following Environmental Tobacco
Smoke Exposure
http://niches.duke.edu/
2013
Duke
University
Investigate the relationship between
environmental tobacco smoke and brain
function in children. Explain how environmental
tobacco smoke increases the risk of attention
deficit hyperactivity disorder through epigenetic
alterations.
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Table 2. NIEHS/EPA Children's Environmental Health and Disease Prevention Research Centers
Center Name
Year
Funded
Institution
Research Goals
Southern California Children's
Environmental Health Center
http://hvdra. usc.edu/cehc/
2013
University of
Southern
California
Understand the impact of near-roadway air
pollution on childhood obesity and diabetes.
Children's Environmental Health
and Disease Prevention Research
Center at Dartmouth
httD://www.dartmouth.edu/~chil
drenshealth/
2013
Dartmouth
College
Understand the impact of arsenic in drinking
water and food on children's health. Inform the
public about how to minimize health risks from
arsenic.
Center for Environmental
Research and Children's Health
http://cerch.org/
2009
University of
California,
Berkley
Investigate the health effects of pesticides,
including DDT and manganese, and PBDE flame-
retardants in boys approaching puberty. Explore
whether pesticide exposure to children affects
development and timing of puberty.
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Table 3 lists the previously funded NIEHS/EPA Children's Centers that closed in FY16. Those Centers
marked with an asterisk are continuing research under a different grant.
Table 3. NIEHS/EPA Children's Centers CLOSED in FY16
Center Name
Year
Funded
Institution
Research Goals
The Columbia Center for Children's
Environmental Health*
htto://ccceh. or a/
2015
Columbia
University
Explore the role of polyaromatic
hydrocarbons and BPA in the
development of obesity, metabolic
syndrome, and neurodevelopmental
disorders in children. Explore the
epigenetic mechanisms that
mediate the effects of these
chemicals on disease.
Mechanisms of Asthma - Dietary
Interventions against Environmental
Triggers*
httos://cfoub. eoa.aov/ncer abstracts/inde
x. cfm/fuseaction/disDlav. abstractDetail/ab
stract/9218
2009
Johns Hopkins
University
Understand how diet influences the
asthmatic response to indoor and
outdoor airborne pollutants and
allergens. Translate findings into
practical dietary strategies to
improve pediatric asthma health.
Explore the mechanisms related to
airway inflammation, oxidative
stress, and respiratory morbidity in
inner-city African-American
children.
Center for Integrative Research on
Childhood Leukemia and the Environment*
htto://circte. berkelev. edu/
2015
University of
California,
Berkeley
Examine the interplay of
environmental, genetic, and
epigenetic factors related to the risk
of leukemia in children. Evaluate the
effects of exposures to chemicals
such as pesticides, polychlorinated
biphenyls, and PBDEs on childhood
leukemia.
Center for Child Environmental Health Risks
Research
httos://www. eoa.aov/research-
arants/niehseoa-cehcs-center-child-
environmental-health-risks-research-
universitv
2003
University of
Washington
Understand factors that increase
susceptibility to the adverse effects
of pesticides. Improve
understanding of critical pathways
of exposure to pesticides for
children. Identify mechanisms for
the adverse developmental
neurotoxicity of pesticides.
* Research is continuing under a different grant.
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Children's Center Publications
The Children's Centers published at least 135 papers in 2015 and 69 papers in 2016 (to date). A few
publications from the Children's Centers are highlighted below.
Hiahliahted publications
Children Exposed to Organophosphate Pesticides Early in
Life Showed Decreased Lung Function
Findings from the NIEHS/EPA Children's Center at the
University of California, Berkeley, link organophosphate
pesticide metabolites in the urine of 279 children living in
California's Salinas Valley that have decreased lung function.
This decrease in lung function is similar to the decrease seen
in response to a child's exposure to secondhand smoke. The
findings are the first to link chronic, low-level exposures of
organophosphate pesticides to lung health for children.
Persistent reduced lung function during childhood increases
the risk for chronic obstructive pulmonary disease in
adulthood, http://thorax.bmi.eom/content/71/2/148.
Infants Who Ate Rice, Rice Products Had Higher Urinary
Concentrations of Arsenic
Epidemiology evidence suggests that arsenic exposure in
utero and in early life is associated with adverse effects on
fetal growth, as well as on infant and child immune and
neurodevelopment outcomes. Arsenic has been found in
rice and rice products, which are typical first foods for
infants. To investigate the potential exposure from dietary
sources of arsenic, a new study by the NIEHS/EPA Children's Center at Dartmouth College found that
infants who ate rice products had higher urinary arsenic concentrations than those who consumed no
rice. The study concludes that consumption of rice and rice products increases infants' exposure to
arsenic and that efforts should be made to reduce arsenic exposure during critical periods of
development. http://archpedi.iamanetwork.com/article.aspx?articleid=2514074.
Prenatal Exposure to BPA Linked to Measures of Body Fat during Childhood
Researchers from the NIEHS/EPA Children's Center at Columbia University have shown that prenatal
exposure to BPA, a chemical widely used in plastic water bottles and metal cans lined with BPA-
containing resin, might contribute to obesity development in young children. This study is the first to
show a possible link between prenatal exposures to BPA and measures of body fat in school-aged
children. Children exposed to higher concentrations of prenatal BPA had higher levels of adiposity.
http://ehp.niehs.nih.gov/EHP205/.
Early Exposures to Phthalates and BPA Interfere with Metabolism
m
Community members at a meeting of the
University of Washington Children's Center
to learn about dimethylthiophosphate levels
detected in their urine during a study. They
also obtained more information on
pesticides and how to reduce pesticide
exposure at home and in the workplace.
Selected quotes from the meeting:
• "I know the importance of sometimes getting
that information of what the pesticides
contain and what they can do to
people....These findings are important."
• "Why do we do research? Well,, to learn how
to prevent illness and all of that."
15
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Endocrine-disrupting chemicals such as phthalates, polychlorinated biphenyls, and BPA might produce
adverse developmental, reproductive, neurological, and immune effects. Researchers from the
NIEHS/EPA Children's Center at the University of Michigan explored associations between in utero BPA
concentrations and markers of peripubertal metabolic homeostasis. The results show phthalates and
BPA were associated with metabolism biomarkers at ages 8-14 years in patterns that varied by sex and
pubertal status, http://press.endocrine.org/doi/full/10.1210/ic.2015-2706.
Conferences and Meetings
2015 NIEHS/EPA Children's Centers Annual Meeting.
Washington D.C., October 29 and 30, 2015. More than 260
participants registered for this annual event including
researchers from the NIEHS/EPA Children's Centers and the
PEHSUs, scientists from Federal agencies, and others. The
agenda was developed to explore connections between
research findings, clinical practice, and community outreach
and translation. Speakers also discussed approaches for
communicating research findings and technical information
with parents and the public.
2015 Congressional Briefing. "A Healthy Start for Every
Child: How the Environment Influences Health &
Development" was held at the Rayburn House Office
Building, on October 28, 2015. Accomplishments from the
NIEHS/EPA Children's Centers were presented.
NIEHS/EPA Children's Centers Webinar Series. Monthly, in
collaboration with the EPA Office of Children's Health
Protection. The webinar series focused on topics related to
children's environmental health, including childhood
obesity, epigenetics, childcare, neurodevelopment, and
prenatal exposures. The webinars featured researchers from
the NIEHS/EPA Children's Centers, PEHSUs, EPA, and the
National Institutes of Health (NIH). Participation ranged between 150 and 300 people from a wide
variety of backgrounds, including researchers, clinicians, scientists, representatives of professional
organizations, and the public.
Other STAR Grants Addressing CEH Research
Table 4 highlights active STAR grants, funded by the ACE, CSS, and SHC research programs that focus on
children's environmental health. These grants represent a significant investment in complementary
areas of CEH research and are in addition to the NIEHS/EPA Children's Centers summarized in Table 2
and Table 3. For example, the seven Healthy Schools STAR research grants listed in Table 4 have initiated
efforts investigating important linkages between building characteristics and indoor air quality, and their
Research Impact
FDA proposed limit for inorganic
arsenic in infant rice cereal cites
research from the NIEHS/EPA
Children's Centers
In April 2016, the Food and Drug
Administration (FDA) proposed a limit
for inorganic arsenic in infant rice
cereal, citing the work of the
NIEHS/EPA Children's Center at
Dartmouth College. This Center has
been funded by the two agencies
under two separate grants since
2010.
The new limits on arsenic in infant
rice cereal have received coverage by
close to 500 news outlets including
the New York Times and NBC News.
Link to FDA press release:
http://www.fda.gov/NewsEvents/Ne
wsroom/PressAnnouncements/ucm49
3740.htm
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subsequent relationships to children's learning performance. In FY16, these grantees worked toward
developing informational tools, databases, and models to help design construction and operation
practices to foster safe and healthy school environments and maximize student achievement and
teacher and staff effectiveness in K-12 schools.
Table 4. Other National Center for Environmental Research/EPA STAR Grants
Addressing CEH Research
Institution Name
Year Funded
Research Focus;
Research Program
Topic Area
Colorado State Universitv
2015
Healthy Schools
Research Grant; SHC
Sustainable Places, Health, and
Educational Research in Schools
Johns Hopkins Bloomberg School of
Public Health; Baltimore Citv
Schools; Baltimore Education
Research Consortium
2015
Healthy Schools
Research; SHC
Baltimore Healthy Schools: Impact
of Indoor Air Quality on Health and
Performance
Universitv of Texas, Austin
2015
Healthy Schools
Research; SHC
Healthy High School Partnership in
Research on Indoor Environments
Health Research Inc.; NYS
Department of Health
2014
Healthy Schools
Research; SHC
Assessment of School
Environmental Effects on
Children's Health and Performance
and Strengthening of
State/Community Capacity to
Create a Healthy and Safe Learning
Environment
Universitv of Michigan; Wavne
State Universitv
2014
Healthy Schools
Research; SHC
Environmental Quality, Health, and
Learning in Conventional and High
Performance School Buildings
Universitv of Nebraska, Lincoln
2014
Healthy Schools
Research; SHC
Evidence-Based Interactions
between Indoor Environmental
Factors and their Effects on
Kindergarten-12 Student
Achievement
Universitv of Oklahoma; Colorado
State Universitv; Universitv of
Oklahoma Health Sciences Center
2014
Healthy Schools
Research; SHC
Balancing Sustainability, Clean Air,
Healthy Learning Interiors, and
Structural Safety when Designing
and Building Schools
Boston Universitv; Duke Universitv
2014
New Methods in 21st
Century Exposure
Science; CSS
Residential Exposure of Young
Children to Semivolatile Organic
Compounds
Universitv of California, San
Francisco
2014
New Methods in 21st
Century Exposure
Science; CSS
Non-targeted Method for
Measuring Multiple Chemical
Exposures among a
Demographically Diverse
Population of Pregnant Women in
Northern California
17
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Table 4. Other National Center for Environmental Research/EPA STAR Grants
Addressing CEH Research
Institution Name
Year Funded
Research Focus;
Research Program
Topic Area
University of Washington
2014
Organotypic Culture
Models for Predictive
Toxicology; CSS
Predictive Toxicology Center for
Organotypic Cultures and
Assessment of AOPs for
Engineered Nanomaterials
University of Wisconsin, Madison
2014
Organotypic Culture
Models for Predictive
Toxicology; CSS
Human Models for Analysis of
Pathways Center
Vanderbilt University; University of
Pittsburgh
2014
Organotypic Culture
Models for Predictive
Toxicology; CSS
Vanderbilt-Pittsburgh Resource
for Organotypic Models for
Predictive Toxicology
Little Big Horn College; Montana
State University
2014
Tribal Environmental
Health; SHC
Water, Our Voice to the Future:
Climate Change Adaptation and
Waterborne Disease Prevention on
the Crow Reservation
University of Massachusetts -
Amherst; Rverson University;
University of Toronto
2014
Tribal Environmental
Health; SHC
Subsistence Hunting and
Associated Activities of Native
North Americans in Remote
Communities: Measurement of
Indoor Air Quality in Tents as
Related to Wood-Smoke
Exposures, and the Identification
of Potential Health Risks
University of Tulsa; Cherokee
Nation Environmental Program and
Health Services; Institute for Tribal
Environmental Professionals;
Navaio Nation - EPA and
Department of Dine Education;
Nimiipuu Health; University of
Oklahoma
2014
Tribal Environmental
Health; SHC
From Home to School: Tribal
Indoor Air Quality Intervention
Study
Harvard University
2011
Clean Air Research
Center; ACE
Air Pollution Mixtures: Health
Effects Across Life Stages
Emory University; Georgia Institute
of Technology; University of
Nevada, Reno
2010
Clean Air Research
Center; ACE
Southeastern Center for Air
Pollution and Epidemiology: Multi-
Scale Assessment of Health Effects
of Air Pollution Mixtures Using
Novel Measurements and Models
18
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Ilenges & Opportunities
Changes in the Broader Scientific and Policy Landscape with Impact on CEH Research
FY16 presented a historic opportunity for EPA with the enactment of Frank R. Lautenberg Chemical
Safety for the 21st Century Act (H.R. 2576). This Act modernizes the Toxic Substances Control Act (TSCA),
and introduces several new provisions relevant to CEH:
• Protection of potentially exposed or susceptible subpopulations: The term "potentially
exposed or susceptible subpopulation" means a group of individuals within the general
population identified by the EPA Administrator who—due to either greater susceptibility or
greater exposure—might be at greater risk than the general population for adverse health
effects from exposure to a chemical substance or mixture, such as infants, children, or pregnant
women. Moving forward, CEH research will need to be translated for application to chemical
evaluations or risk assessments of new or existing substances for potential or differential harm
to this subpopulation. For EPA, effective translation will require advancing the science to
integrate diverse data streams—including conventional and molecular epidemiology, animal and
computational toxicology, and exposure science—for practical application to regulatory risk
assessments.
• Chemical inventory reset: The new law requires EPA to reevaluate the chemical inventory for
existing and new chemicals or mixtures and prioritize those for potential to cause harm.
• Focus on exposure characterization: Rather than focusing on toxicity alone, this prioritization
requires considering exposures up front and as components of chemical evaluations.
• Predictive capacity: The new law emphasizes the need to predict chemical impacts to human
health and the environment before commercialization. This focus on predictive capacity is well
aligned with the systems approach outlined in the CEH Research Roadmap.
• Reduction in vertebrate testing: Although section 4 of the new law allows EPA to require
additional testing, it also requires EPA to reduce and replace, to the extent practicable and
scientifically justified, the use of vertebrate animals in testing chemical substances and mixtures.
EPA's research in the Chemical Safety for Sustainability National Research Program is well positioned to
support EPA's implementation of the new law:
• CSS researchers have developed methods for "nontargeted" and "suspect screening" analyses,
to demonstrate novel applications of these methods for analyses of household dust for human
exposures and analyses of natural waters for perfluorinated compounds. These approaches
provide a platform for future research designed to identify and quantify emerging unstudied
contaminants rapidly in media that are relevant to children's environmental health.
• In a continued commitment to improve the public's access to data, CSS scientists released a new
interactive Chemistry Dashboard with chemistry information for over 700,000 chemicals. The
publicly available dashboard is a gateway to an array of related public domain databases,
provides improved access to data and models associated with chemicals of interest, and is a hub
19
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that links many EPA research databases. The user-friendly interface, which provides access to
chemical structure information and tens of thousands of physicochemical properties, is used to
develop machine-learning models. The Chemistry Dashboard brings EPA a step closer to a "one-
stop-shop" for data needs regarding environmental chemistry data that inform exposure and
risk assessments.
• Under the new law, risk assessors will face increasing demands to assess more chemicals, with
greater speed and accuracy, and to do so using fewer resources and experimental animals. New
approaches in biological and computational sciences provide mechanistic information that could
help in meeting these challenges. AOP provides a conceptual platform that organizes existing
knowledge about the linkage between a direct molecular initiating event and an adverse
outcome at a biological level of organization relevant to risk assessment. A series of CSS
publications in FY16 (for example, organizing information for improved decision-making and
using AOPs to link exposures to high-throughput screening data), demonstrates how
applications of AOPs will improve chemical safety decisions.
Across all of ORD's National Research Programs, full consideration of at-risk populations in public health
decision-making is a significant focus. Due to cumulative assault from ubiquitous environmental
contaminants resulting from crumbling infrastructures, residual and ongoing pollutant exposures to lead
and other metals, polychlorinated biphenyls (PCBs, especially in schools), perfluorinated compounds
(PFCs), coal combustion waste, and other sources, children suffer from myriad impacts. Impacts include
adverse developmental health, neurological impacts, obesity, asthma, hormone disruption (such as early
onset of puberty), and cancers. Research to improve our understanding of factors affecting exposure
and health outcomes will provide a scientific basis for cumulative assessment and help identify risk
management options. These factors include key lifestages and subpopulations along with complex
influences on health of cumulative exposures to chemical and nonchemical pollution (e.g., noise) and
nonpollutant stressors (e.g., access to healthcare, healthy foods, violence, poverty, loss of social
connection).
Improving Integration of Research Projects across ORD
The CEH Research Roadmap created a common research agenda and shared platform for ORD. ORD's
National Research Programs have each developed cross-disciplinary research projects, but integration
across the National Research Programs remains challenging. To begin addressing integration challenges,
ORD formed the CEH IWG in FY16. ORD researchers, ORD National Research Program leadership, and
EPA Program Office and Regional partners comprise the CEH IWG. Meeting on a monthly basis, the CEH
IWG strives to stimulate dialogue vital for cross-program collaboration, to identify and prioritize CEH
issues, and to serve as a resource on CEH science across EPA. This cross-program representation will
continue to facilitate integration across ORD's research projects and leverage ongoing efforts to
implement the strategic vision of the CEH Research Roadmap with efficiency. A focus for FY17 is
identifying additional opportunities to integrate across National Research Programs and with the other
cross-ORD Research Roadmaps on Nitrogen and Co-Pollutants, Climate Change, and Environmental
Justice.
20
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II. J
A. Near-tciiii II search I imi
With the establishment of the CEH IWG and the funding of several extramural grants and Centers, the
year ahead holds great promise. ORD intramural CEH research efforts are in full swing, with
approximately 40 publications anticipated for release in the first half of FY17. EPA will continue to
partner with other Federal agencies, academia, and independent organizations to further CEH research.
FY17 research will continue to apply complex systems science to integrate the rapidly expanding body of
information on children's health. This information will be translated into tools and databases to support
Agency decisions that promote and protect children's health and well-being. As was done in FY16 for
lead, perchlorate, tire crumbs, Zika, and other topics, Agency priority to protect children's health will
inform research focus and resource prioritization, allocation, and redistribution. Emerging areas, such as
the role of human and environmental microbiomes in influencing children's health and the
environmental determinants of cancer and critical lifestage exposures, will be incorporated into existing
research plans of the National Research Programs. The focus on thyroid research will continue to be
integrated into the broader understanding of neurodevelopmental health. Most importantly, the
CEH IWG will increase its efforts to translate the science and facilitate the dissemination of emerging
science, both across EPA and with its stakeholders.
IB. Proposed Meetings and Workshops
The Children's Centers will present at the Environmental Health Science Facilities, Engagement,
Scientific Advancement, and Training meeting, on December 5-8, 2016 in Durham, North Carolina. The
NIEHS Division of Extramural Research will host the multiday event, which grantees, community
partners, and EPA-NIEHS scientists will attend. The meeting is aimed at stimulating innovation in
research approaches, communication, translational research, tools, sensors, and more; highlighting
scientific accomplishments around crosscutting themes; and sharing best practices among the scientific
community.
OCM Centers are planning a meeting in conjunction with the Society of Toxicology Annual Meeting in
2017. This meeting will feature research by early-career scientists, encourage additional collaboration
among the Centers and other related research in ORD, and help evaluate the opportunity to integrate
the OCM models in EPA's predictive toxicology research.
In addition, ORD staff, Regions, and many EPA partners will continue to present their research findings
at conferences and professional meetings relevant to children's environmental health throughout FY17.
21
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
This appendix presents ORD's FY16 manuscripts related to children's environmental health that have
been accepted by peer-reviewed journals for publication. This table presents products of intramural
research only. Numerous publications from extramural grants, including STAR Grants, Children's
Centers, and others are tracked by the STAR program and reported publicly as required by that program.
To facilitate review of the list, the articles are loosely organized by research area, such as exposure
evaluation, or health outcome, such as asthma, that were identified as high priority in the CEH Research
Roadmap. As much of the CEH research is crosscutting and transdisciplinary, these publications could be
assigned to multiple categories. In addition, articles that are also relevant to an emerging research area
-early-life determinants of cancer, the microbiome, thyroid disruption—are indicated.
Appendix A. Completed Peer-Reviewed ORD Publications in FY16
National
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Program
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-C
H
Adverse Birth Outcomes
Beggs KM, McGreal SR, McCarthy A, Gunewardena S, Lampe JN, Lau C, Apte U.
The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic and
CSS
•
perfluorooctanesulfonic acid-induced hepatocellular dysfunction. Toxicol Appl
Pharmacol, Aug 1; 304:18-29, (2016).
Douglas G, Thirkill T, Kumar P, Loi M, Hilborn E. Effect of Microcvstin-LR on
human placental villous trophoblast differentiation in vitro. Environmental
SSWR
•
Toxicology, John Wiley & Sons, Ltd., Indianapolis, IN, USA, 31(4): 427-39, (2016).
El-Masri H, Kleinstreuer N, Hines RN, Adams L, Tal T, Isaacs K, Wetmore BA, Tan
YM. Life-stage physiologically based pharmacokinetic (PBPK) model application
to screen environmental hazards using adverse outcome pathways (AOPs) and
CSS
environmental exposure models. ToxicolSci, Jul: 152(l):230-43, (2016).
Jarema K, Hunter D, Shaffer R, Behl M, Padilla S. Acute and developmental
behavioral effects of flame retardants and related chemicals in zebrafish.
CSS
Neurotoxicology and Teratology, Elsevier Science Ltd, New York, NY, USA, 52:
194-209, (2015).
Leung MCK, Hutson S, Seifert A, Spencer R, Knudsen T. Computational modeling
and simulation of genital tubercle development. Reproductive Toxicoloav,
Elsevier Science Ltd, New York, NY, USA, 1-11, (2016a).
CSS
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
Citation
National
Research
Program
Cancer
Microbi
Thyroid
Adverse Birth Outcomes
Leung M, Phuong J, Baker N, Sipes N, Klinefelter G, Martin M, McLaurin K, Setzer
W, Darnev S, Judson R, Knudsen T. Systems toxicology of male reproductive
development: Profiling 774 chemicals for molecular targets and adverse
CSS
outcomes. Environmental Health Perspectives, 124(7), (2016b).
Makris, SL, Scott CS, Fox J, Knudsen, TB, Hotchkiss AK, Arzuaga X, Euling SY,
Powers CM, Jinot J, Hogan KA, Abbott BD, Hunter SE, Michael G, Narotsky MG. A
systematic evaluation of the potential effects of trichloroethvlene exposure on
CSS
cardiac development. Reproductive Toxicoloav, in press (2016).
Poet, T., Schlosser, P., Rodriguez, C., Parod, R., Rodwell, D., Kirman, C. Using
physiologically based pharmacokinetic modeling and benchmark dose methods
CSS
to derive an occupational exposure limit for N-methvlpyrrolidone. Regulatory
Toxicology and Pharmacology, Volume 76, April 2016, Pages 102-112, ISSN 0273-
2300, http://dx.doi.Org/10.1016/j.yrtph.2015.12.020.
Rappazzo K, Daniels J, Messer L, Poole C, Lobdell D. Exposure to the elemental
carbon, organic carbon, nitrate and sulfate fractions of fine particulate matter
ACE; SHC
and risk of preterm birth in New Jersey, Ohio, and Pennsylvania (2000-2005).
Environmental Health Perspectives, National Institute of Environmental Health
Sciences (NIEHS), Research Triangle Park, NC, USA, 123(10): 1059-65, (2015).
Rappazzo K, Warren J, Meyer R, Herring A, Sanders A, Brownstein N, Luben T.
Maternal residential exposure to agricultural pesticides and birth defects in a
HHRA
2003 to 2005 North Carolina birth cohort. Birth defects research part a: clinical
and molecular teratology. John Wiley & Sons, Ltd., Indianapolis, IN, USA, 1-10,
(2016).
Rogers, J. Search for the missing Incs: gene regulatory networks in neural crest
development and long non-coding RNA biomarkers of Hirschsprung's disease.
CSS
Neurogastroenterology & Motility', John Wiley & Sons, Inc., Hoboken, NJ, USA,
28(2): 161-166, (2016).
Tal T, Kilty C, Smith A, LaLone C, Kennedy B, Tennant A, McCollum C, Bondesson
M, Knudsen T, Padilla S, Kleinstreuer N. Screening for chemical vascular
disruptors in zebrafish to evaluate a predictive model for developmental vascular
toxicity, in review (2016).
CSS
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
Citation
National
Research
Program
Cancer
Microbi
Thyroid
Adverse Birth Outcomes
Theunissen PT. Comparing rat and rabbit embryo-fetal developmental toxicity
studies for 379 pharmaceuticals: On systemic dose and developmental effects.
Crit Rev Toxicol, in press (2016).
CSS
Asthma
Chen C, Chao HJ, Shen W, Chen B, Lin, K, Guo YL, Vesper, S. Pilot studv of mold in
homes of asthmatic children in Taipei, Taiwan, using the Environmental Relative
N/A
•
Moldiness Index. Aerobiolopia, Springer, New York, NY, USA, 31(2): 213-218,
(2015).
Ghio, AJ. Asthma as a disruption in iron homeostasis. Biometals, Springer
Netherlands, 29: 751, (2016).
SHC
Snow S, Gordon C, Bass V, Schladweiler M, Ledbetter A, Jarema K, Phillips P,
Johnstone A, Kodavanti, U. Age-related differences in pulmonary effects of acute
and subchronic episodic ozone exposures in brown Norway rats. Inhalation
SHC
Toxicology, Informa Healthcare USA, New York, NY, USA, 28(7): 313-23, (2016).
Vesper S, Prill R, Wvmer L, Adkins L, Williams R, Fulk, F. Mold contamination in
schools with either high or low prevalence of asthma. Pediatric Allerav and
SHC
•
Immunology, John Wiley & Sons, Inc., Hoboken, NJ, USA, 26(1): 49-53, (2015).
Vesper S, H Choi, M Perzanowski, L Acosta, A Divjan, B Bolanos-Rosero, F Rivera-
Mariani, G Chew. Mold populations and dust mite allergen concentrations in
house dust samples from across Puerto Rico. International Journal of
Environmental Health Research, Carfax Publishing Limited, Basingstoke, UK,
26(2): 198-207, (2016a).
SHC
•
Vesper S, Wvmer L. The relationship between environmental relative moldiness
index values and asthma. International Journal Of Hvaiene And Environmental
Health, Urban & Fischer Verlag Jena, Jena, Germany, 219(1): 233-238, (2016).
SHC
•
Vesper S, Robins T, Lewis T, Dombkowski K, Wymer L, Villegas R, Batterman Use
of Medicaid and housing data mav help target areas of high asthma prevalence.
SHC
•
J Asthma, Jul 19:0, (2016b).
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
National
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H
Endocrine Disruption
Armstrong B, J Lazorchak, K Jensen, H Haring, ME Smith, R Flick, D Bencic, A
Biales. Reproductive effects in fathead minnows (Pimeohales promelas)
following a 21-d exposure to 17 alpha-ethinylestradiol. Chemosphere, Elsevier
N/A
Science Ltd, New York, NY, USA, 144(1): 366-373, (2015).
Cavallin J, A Schroeder, K Jensen, D Villeneuve, B Blackwell, K Carlson, M Kahl, C
La Lone, E Randolph, G Anklev. Evaluation of whole-mount in situ hybridization as
a tool for pathwav-based toxicological research with earlv-life stage fathead
CSS
minnows. Aauatic Toxicoloav, Elsevier Science Ltd, New York, NY, USA, 169: 19-
26, (2015).
Gray, E, J Furr, K Tatum-Gibbs, C Lambright, H Sampson, B Hannas, V Wilson, A
Hotchkiss, P Foster. Establishing the biological relevance of dipentvl phthalate
reductions in fetal rat testosterone production and plasma and testis
SHC
testosterone levels. Toxicoloaical Sciences. Society of Toxicology, 149(1): 178-91,
(2016).
Howdeshell, K, C Rider, V Wilson, J Furr, C Lambright, E Gray. Dose addition
models based on biologically relevant reductions in fetal testosterone accurately
CSS
predict postnatal reproductive tract alterations by a phthalate mixture in rats.
Toxicological Sciences. Society of Toxicology, 148(2): 488-502, (2015).
Karmaus, A, C Toole, D Filer, K Lewis, M Martin. High-throughput screening of
chemical effects on steroidogenesis using H295R human adrenocortical
CSS
carcinoma cells. Toxicoloaical Sciences. Society of Toxicology, 150(2): 323-332,
(2016).
Leonard, J, Tan, Y, Gilbert, M, Isaacs, K, El-Masri, H. Estimating margin of
exposure to thyroid peroxidase inhibitors using high-throughput in vitro data,
CSS
high-throughput exposure modeling, and physiologically based
pharmacokinetic/pharmacodynamic modeling. Toxicoloaical Sciences. May 15,
2016 (1): 57-70. Epub 2016 Feb 10.
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
National
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Research
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
Citation
National
Research
Program
Cancer
Microbi
Thyroid
Epigenetics
Perumal-Kuppusamy, S, P Kaiser, S Wesselkamper. Epigenetic regulation in
environmental chemical carcinogenesis and its applicability in human health risk
HHRA
•
assessment. International Journal ofToxicoloav. Taylor & Francis, Inc.,
Philadelphia, PA, USA, 5(34): 384-392, (2015).
Vidal, A, V Semenova, T Darrah, A Vengosh, Z Huang, K King, M Nye, R Fry, D
Skaar, R Mcguire, A Murtha, J Schildkraut, S Murphy, C Hovo. Maternal cadmium,
iron and zinc levels, DNA methvlation and birth weight. BMC Pharmacoloav and
SHC
Toxicology, BioMed Central Ltd, London, UK, 15: 16-20, (2015).
Exposure Evaluation
Arnold, B, T Wade, J Benjamin-Chung, K Schiff, J Griffith, A Dufour, S Weisberg, J
Colford. Acute gastroenteritis and recreational water: highest burden among
young us children. American Journal of Public Health. American Public Health
Association, Washington, DC, USA, 106(9): 1690-97, (2016).
SSWR;
SHC
Bennett, DH, RE Moran, X Wu, N Tulve, M Clifton, M Colon, W Weathers, A
Siodin, R Jones, 1 Hertz-Picciotto. Polvbrominated diphenvl ether (PBDE)
concentrations and resulting exposure in homes in California: relationships
SHC
among passive air, surface wipe and dust concentrations, and temporal
variability. Indoor Air. Blackwell Publishing, Maiden, MA, USA, 25(2): 220-229,
(2015).
Betancourt, D, T Dean, J Kim, J Lew. Genome seauence of Stachvbotrvs
chartarum Strain 51-11. Genome Announcements. American Societv for
Microbiology, Washington, DC, USA, 3(6): 1114-1115, (2015).
N/A
Bost, C., Strynar, M., Reiner, J., Zweigenbaum, J., Secoura, P., Lindstrom, A., Dye,
J. U.S. domestic cats as sentinels for perfluoroalkvl substances: Possible linkages
CSS
with housing, obesity, and disease. Environmental Research. Volume 151,
November 2016, Pages 145-153
Chien, L, M Tsou, H Hsi, P Beamer, K Bradham, Z Hseu, S Jien, C Jiang, W Dang,
H Oumlzkavnak. Soil ingestion rates for children under 3 years old in Taiwan.
Journal of Exposure Science and Environmental Epidemiology, Nature Publishing
Group, London, UK, online, (2015).
SHC
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
National
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£
H
Exposure Evaluation
Fulk, F, E Havnes, T Hilbert, D Brown, D Petersen, T Reponen. Comparison of
stationary and personal air sampling with an air dispersion model
SHC
for children's ambient exposure to manganese. Journal of Exposure Science and
Environmental Epidemiology, Nature Publishing Group, London, UK, online,
(2016).
Funk, W, J Pleil, DJ Sauter, TW McDade, JL Holl. Use of dried blood spots for
estimating children's exposures to heavy metals in epidemiological research.
ACE
Journal of Environmental & Analytical Toxicology, OMICS Publishing Group, Los
Angeles, CA, USA, 7: 002, (2015).
Kaminski, M, S Lee, M Magnuson. Wide-area decontamination in an urban
environment after radiological dispersion: A review and perspectives.
HSRP
Environmental Science & Technology, American Chemical Society, Washington,
DC, USA, 305: 67-86, (2015).
Marchitti, SA, Fenton, SE, Mendola, P, Kenneke, JF, Hines, EP. Polvbrominated
diphenvl ethers in human milk and serum from the US EPA MAMA studv:
CSS
Modeled predictions of infant exposure and considerations for risk assessment.
Environmental Health Perspectives, Jul 12. (2016).
McEwen, A, H Hsu-Kim, N Robins, N Hagan, S Halabi, O Barras, D Richter, J
Vandenberg. Residential metal contamination and potential health risks of
exposure in adobe brick houses in Potosiacute, Bolivia. Science of the Total
HHRA
Environment, Elsevier BV, Amsterdam, Netherlands, 562: 237-246, (2016).
Melnvk, L., Wang, Z., Li, Z., Xue, J. Prioritization of pesticides based on dailv
dietary exposure potential as determined from the SHEDS model. Food and
CSS
Chemical Toxicology, 96: 167-173, ISSN 0278-6915, (2016).
Morgan, M, P Jones, J Sobus, J Chuang, NK Wilson. Using urinary biomarkers to
evaluate polycyclic hydrocarbon exposures in 126 preschool children in Ohio.
SHC
International Journal of Environmental Health Research, Carfax Publishing
Limited, Basingstoke, UK, 25(6): 628-639, (2015).
Obrvcki, J, N Basta, K Scheckel, B Stevens, K Minca. Phosphorus amendment
efficacy for in situ remediation of soil lead depends on the bioaccessible method.
SHC
Elizabeth Guertal, David Myroid, C. Wayne Smith. Journal of Environmental
Quality, American Society of Agronomy, Madison, Wl, USA, 45(1): 37-44, (2016).
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
Citation
National
Research
Program
Cancer
Microbi
Thyroid
Exposure Evaluation
Pawlak, E, TL Noah, H Zhou, C Chehrazi, C Robinette, D Diaz-Sanchez, L Muller, 1
Jaspers. Diesel exposure suppresses natural killer cell function and resolution of
eosinophil inflammation: A randomized controlled trial of exposure in allergic
ACE
rhinitics. Particle and Fibre Toxicoloav. BioMed Central Ltd, London, UK, 13(1):
24, (2016).
Platten, W, N Sylvest, C Warren, M Arambewela, S Harmon, K Bradham, K
Rogers, T Thomas, T Luxton. Estimating dermal exposure to copper nanoparticles
from the surfaces of pressure-treated lumber and implications for toxicity. D.
CSS
Barcelo Culleres, J. Gan. Science of the Total Environment, Elsevier BV,
Amsterdam, Netherlands, 548: 441-449, (2016).
Schonfeld, T. Ethical considerations in development of future therapies for
women and children. Chapter 12, Hughes, Claude L., Waters, Michael D. (ed.),
Translational Toxicology, Springer International Publishing AG, Cham (ZG),
Switzerland, 1(1): 339-371, (2016).
N/A
Taubel, M, A Karvonen, T Reponen, A Hyvarinen, S Vesper, J Pekkanen.
Application of the environmental relative moldiness index in Finland. Applied
SHC
•
and Environmental Microbiology. American Society for Microbiology,
Washington, DC, USA, 82(2): 578-584, (2016).
Starr J.M., Li, W., Graham, S.E., Bradham, K.D., Stout li, D.M., Williams, A., Sylva,
J. Using paired soil and house dust samples in an in vitro assav to assess the post
SHC
ingestion bioaccessibilitv of sorbed fipronil. J Hazard Mater. Jul 15; 312:141-9,
(2016).
Taubel, M., A. Karvonen, T. Reponen, A. Hyvarinen, S. Vesper, and J. Pekkanen.
Application of the Environmental Relative Moldiness Index in Finland. Applied
SHC
•
and Environmental Microbiology. American Society for Microbiology,
Washington, DC, USA, 82(2): 578-584, (2016).
Winston, J. J., Emch, M., Meyer, R. E., Langlois, P., Weyer, P., Mosley, B., Luben,
T. (2016). Hypospadias and maternal exposure to atrazine via drinking water in
the National Birth Defects Prevention study. Environmental Health: A Global
Access Science Source, 15(1), [76],
CSS
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
National
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T3
Research
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
Citation
National
Research
Program
Cancer
Microbi
Thyroid
Neurodevelopmental Disorders
Herr, D, Freeborn, D, Degn, L, Martin, SA, Ortenzio, J, Pantlin, L, Hamm, C, Boyes,
W. neurophvsiological assessment of auditory, peripheral nerve, somatosensory,
ACE
and visual system function after developmental exposure to gasoline, el5 and
e85 vapors. Neurotoxicoloav and Teratoloav, Elsevier Science Ltd, New York, NY,
USA, 54: 78-88, (2016).
Brown, J, Hall, D, Frank, C, Wallace, K, Mundv, W, Shafer, T. Evaluation of a
microelectrode array-based assay for neural network ontogeny using training set
CSS
chemicals. Toxicol. Sci. In Press Aug 4, 2016.
Cotterill, E, Hall, D, Wallace, K, Mundv, W, Eglen, S, Shafer, T. characterization of
early cortical neural network development in multiwell microelectrode array
CSS
plates. J. Biomolec Screen. 21: 510-19, (2016).
Druwe, 1, T Freudenrich, K Wallace, T Shafer, W Mundv. Comparison of human
induced pluripotent stem cell-derived neurons and rat primary cortical neurons
CSS
as in vitro models of neurite outgrowth. Applied In vitro Toxicoloav. Mary Ann
Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).
Gilbert, M, K Sanchez-Huerta, C Wood. Mild thyroid hormone insufficiency
during development compromises activity-dependent neuroplasticitv in the
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hippocampus of adult male rats. Endocrinoloav. Endocrine Society, 157(2): 774-
87, (2016).
Herr, D, Freeborn, D, Degn, L, Martin, SA, Ortenzio, J, Pantlin, L, Hamm, C, Boyes,
W. Neurophvsiological assessment of auditory, peripheral nerve, somatosensory,
ACE
and visual system function after developmental exposure to gasoline, E15 and
E85 Vapors. Neurotoxicoloav and Teratoloav. Elsevier Science Ltd, New York, NY,
USA, 54: 78-88, (2016).
Kraft, A, M Aschner, DA Cory-Slechta, SD Bilbo, W Michael Caudle, S Makris.
Unmasking silent neurotoxicity following developmental exposure to
N/A
environmental toxicants. Neurotoxicoloav and Teratoloav. Elsevier Science Ltd,
New York, NY, USA, 55: 38-44, (2016).
Moser, VC, P Phillip, J Hedge, K McDaniel. Neurotoxicological and thvroid
evaluations of rats developmentallv exposed to tris(l,3-dichloro-2-
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•
propvDphosphate (TDICPP) and tris(2-chloro-2-ethvl)phosphate(TCEP).
Neurotoxicology and Teratology, Elsevier Science Ltd, New York, NY, USA, 52:
236-247, (2015).
A-10
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Appendix A. Completed Peer-Reviewed ORD Publications in FY16
Citation
National
Research
Program
Cancer
Microbi
Thyroid
Neurodevelopmental Disorders
Mundy, W, Padilla, S, Breier, J, Crofton, K, Gilbert, M, Herr, D, Jensen, K, Radio,
N, Raffaele, K, Schumacher, K, Shafer, T, Cowden, J. Expanding the test set:
Chemicals with potential to disrupt mammalian brain development.
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Neurotoxicology and Teratology, Elsevier Science Ltd, New York, NY, USA, 52: 25-
35, (2015).
Ramos, RL, Van Dine, SE, Gilbert, M, Leheste, JR, Torres, G. Neurodevelopmental
malformations of the cerebellar vermis in genetically engineered rats. The
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Cerebellum, Springer International Publishing AG, Cham (ZG), Switzerland, 14(5):
624-31, (2015).
Ruiz, JD, Quackenboss, J, Tulve, N. Contributions of a child's built, natural, and
social environments to their general cognitive ability: A systematic scoping
SHC
review. PLoS ONE, Public Library of Science, San Francisco, CA, USA, 2: e0147741,
(2016).
Spring, SR, Bastian TW, Wang, Y, Kosian, P, Anderson, GW, Gilbert, ME. Thyroid
hormone-dependent formation of a subcortical band heterotopia (SBH) in the
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•
neonatal brain is not exacerbated under conditions of low dietary iron (FeD).
Neurotoxicology Teratology, Jul-Aug; 56:41-6, (2016).
Metabolic Syndrome
Angrish, M, Kaiser, J McQueen, C, Chorley, B. Tipping the balance: Hepatotoxicity
and the four apical key events of hepatic steatosis. Toxicological Sciences. April,
2016: 150(2): 261-8.
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Auerbach, S, D Filer, D Reif, V Walker, AC Holloway, J Schlezinger, S Srinivasan, D
Svoboda, R Judson, JR Bucher, KA Thayer. Prioritizing environmental chemicals
for obesity and diabetes outcomes research: A screening approach using ToxCast
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high throughput data. Environmental Health Perspectives, National Institute of
Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA, 1-50,
(2016).
Gordon, C, K Jarema, A Johnstone, P Phillips. Effect of genetic strain and gender
on age-related changes in body composition of the laboratory rat. Phvsioloav &
SHC
Behavior, Elsevier B.V., Amsterdam, Netherlands, 153(1): 56-63, (2016).
A-ll
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