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NIEHS/EPA CHILDREN'S
ENVIRONMENTAL HEALTH AND DISEASE
PREVENTION RESEARCH CENTERS
IMPACT REPORT
PROTECTING CHILDREN'S HEALTH
WHERE THEY LIVE, LEARN, AND PLAY
EPA/600/R-17/407

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Children's Health Matters

The number
35% p
of children
diagnosed
/
with
/
leukemia
/
has
f\J
increased by
A /
35% over
/\/
the past
/
40 years.1
8.4%
8.4% of
children
in the U.S.
have
asthma.2
ttttttt

t ttttt

tttfttt
1 in 42
8-year-old
ttttttt
boys have
autism.3
ttttttt

ttttttt

Children in the U.S. are at high risk for chronic disease
This may be a result of increasing exposures to environmental toxicants.
Approximately
16,000
premature
births per year
in the U.S. are
attributable to
air pollution.4
Children in
4 million
U.S. households
may be exposed
to high levels of
lead.5
Genetics were once thought
to contribute 90% to autism,
but are now thought to only
contribute 41-56% in boys and
13-16% in girls.
The role of •
environmental
factors in autism
is greater than
previously thought.
60% ofacute
respiratory
infections
in children
worldwide
are related to
environmental
conditions.6
Air pollution
contributes to
600,000
deaths worldwide
in children under
5 years old.8

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Children are uniquely vulnerable to environmental risks
jy, Children's brains, lungs, immune, and
other systems are rapidly developing. Their natural
defenses are less developed than adults; skin and
blood-brain barriers are more permeable, and
metabolic and detoxification pathways are not yet
fully developed.
>r. Children's behavior patterns make
them more susceptible to exposure. They crawl and
play close to the ground, putting them in contact
with dirt and dust. They put their hands, toys, and
other objects in their mouths. They eat, drink, and
breathe more than adults relative to body mass.
Children's environmental health has a significant impact on society

Billion
Annual cost of
childhood asthma
that could be
attributed to
environmental
factors.10
$76.6
Billion
Annual cost of
environmentally
related diseases in
U.S. children.10
q\s eases
rC
$833,000
Total cost for one
child with cancer
(medical costs
and lost parental
wages).11
°/ —^
$11,500 -
$15,600
Lifetime earnings
lost as a result of
the loss of one IQ
point.9

$1.4-2.4
Million
Lifetime cost
of supporting
one person with
autism.12
1
i

L
Environmental exposures in the earliest stages of human development - including before
birth - influence the occurrence of disease later in life. Improving the understanding of
these developmental origins of health and disease is critical to reducing children's
health risks and improving the quality of life for children and their families.

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DISCLAIMER
The research described in this document has been funded jointly by the U.S. Environmental Protection Agency (EPA) under
the Science to Achieve Results (STAR) grants program and the National Institute of Environmental Health Sciences (NIEHS). The
information provided does not necessarily reflect the views of the Agency, and no official endorsement should be inferred. Mention
of trade names or commercial products does not constitute endorsement or recommendation by EPA for use. The information
presented in this summary report is intended to provide the reader with insights about the progress and scientific achievements
of STAR research grants. The report lists the grantees whose research is discussed, and it also indicates where more detailed peer-
reviewed scientific data can be found. This report is not intended to be used directly for environmental assessments or decision
making. Readers with these interests should instead consult the peer-reviewed publications produced by the STAR grants and
conduct necessary/ data quality evaluations as required for their assessments. ICF International provided support under contract with
the EPA (contract number EP-C-14-001). EPA and/or its contractor has received permission to use the images within this document.
Suggested citation: U.S. Environmental Protection Agency. (2017). NIEHS/EPA Children's Environmental Health and Disease
Prevention Research Centers Impact Report: Protecting children's health where they live, learn, and play. EPA Publication No.
EPA/600/R-17/407. Retrieved from https://www.epa.gov/sites/production/fiies/2017-10/documents/niehs epa chiidrens centers
impact report 2017 O.pdf?pdf=chidrens-center-report.
"As we embark on 17 years of outstanding interagency
collaboration, we recognize that we will all gain strength
and momentum by working together to protect the
most vulnerable population - our children."13
-James H. Johnson,Jr., Ph.D., Director, NCER, EPA and Gwen W. Collman, Ph.D.,
Director, Division of Extramural Research & Training, NIEHS

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ACKNOWLEDGMENTS
To the Children's Centers investigators, listed on the right -
thank you! Research takes time and all the findings documented
in this report are a result of your unrelenting perseverance.
Thank you for investing your careers and ingenuity to change
the landscape of children's environmental health. Thank you,
also, for your significant contributions to this document. It has
been awe-inspiring to watch you paint a picture that represents
the extensive impact of your work.
I am indebted to HayleyAja (EPA Student Contractor) and Emily
Szwiec (Association of Schools and Programs of Public Health/
EPA) who made tremendous contributions to the report with
passion, dedication, and determination as both authors and
reviewers. I am truly grateful to Patrick Lau for his support,
expertise, and drive for excellence. The continued support and
guidance from the EPA communications staff, including Kelly
Widener, Pradnya Bhandari, Aaron Ferster, and Annie Kadeli
were instrumental in preparing this report.
Kimberly Gray (NIEHS) has been a constant and determined
partner in documenting the success of the Children's Centers
program and this report would not be possible without her
contributions. Additional support from NIEHS was provided by
Christie Drew, Virginia Guidry, and Anne Thompson.
The development of this report also benefited from the
invaluable comments of more than 20 EPA staff across the
Agency (listed in Appendix A). Valuable input and constructive
recommendations from Martha Berger and the EPA Office of
Children's Health Protection, as well as the Children's Health
Protection Advisory Committee, provided essential guidance on
increasing the impact of the report.
Finally, sincere thanks to the individuals that make this research
possible. The American people who have entrusted us to
discover ways to better protect our children; the diligent staff in
grants, financial, and legal offices at EPA, NIEHS, and the funded
institutions; those who have organized and participated in peer
reviews; the research support staff at the centers; and the
children and parents who invest their time to participate in this
research.
Over the last two decades, this program has been skillfully
managed by various EPA and NIEHS staff — It has been my
privilege to capture a snapshot of the impact of this program.
With sincere gratitude,
Nica Louie
Project Officer, Children's Centers program
NCER, ORD, EPA
CHILDREN'S CENTERS INVESTIGATORS
WHO CONTRIBUTED TO THIS REPORT
Cincinnati: Bruce Lanphear, Kimberly Yolton
Columbia University: Frederica Perera,
Kimberly Burke, Brittany Shea
Dartmouth College: Margaret Karagas, Carolyn
Murray
Denver: Andrew Liu
Duke University: Susan Murphy, Ed Levin,
Jamie Wylie
Emory University: Linda McCauley, P. Barry
Ryan, Nathan Mutic
The Johns Hopkins University: Greg Diette,
Nadia Hansel
Northeastern University: Akram Alshawabkeh
UC Berkeley (CERCH): Brenda Eskenazi, Asa
Bradman, Kim Harley, Nina Holland, Karen Huen,
James Nolan
UC Berkeley (CIRCLE): Catherine Metayer,
Stephen Rappaport, Mark Miller, John Nides,
Joseph Wiemels, Todd Whitehead
UC Berkeley/Stanford University: Katharine
S. Hammond, Jennifer Mann, Kari Nadeau, Mary
Prunicki, Deborah Hussey Freeland
UC Davis: Judy Van de Water, Isaac Pessah, Irva
Hertz-Picciotto
UC San Francisco: Tracey Woodruff, Patrice
Sutton, Erin DeMicco
University of Illinois: Susan Schantz,Jodi Flaws
University of Michigan: Karen Peterson,
Vasantha Padmanabhan, Robin Lee, Dana
Dolinoy,Jacyln Goodrich, Deborah Watkins, Brisa
Sanchez, Wei Perng
University of Southern California: Rob
McConnell, Andrea Hricko,John Froines
University of Washington: Elaine Faustman,
Marissa Smith

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CONTENTS
CHILDREN'S
HEALTH MATTERS
2 HEALTH	1Q ENVIRONMENTAL QjJ
OUTCOMES	ID EXPOSURES OD
IMMUNE FUNCTION	26
Environmental exposures can interfere
with the function and regulation of
the immune system, causing other
health problems such as altered
neurodevelopment and cancer.
REPRODUCTIVE DEVELOPMENT 35
Exposure to environmental chemicals can
affect the timing of puberty for boys and
girls.
EXECUTIVE SUMMARY	8
In just a few pages, learn about the history
of the Children's Centers, their unique
research, and their groundbreaking work.
COMMONLY USED ACRONYMS 16
CENTER NAMES AND AFFILIATIONS 18
A list to help cross-reference center
names and affiliations.
READING GUIDE	17
How to navigate through this report,
whether you need a simple overview or a
more in-depth look at the science.
ASTHMA	20
Examples of how exposures in different
locations such as near roadways or
in rural settings could make asthma
symptoms worse.
BIRTH OUTCOMES	22
Mothers exposed to some environmental
chemicals whiie pregnant may be at
higher risk for babies with preterm birth,
low birth weight, and birth defects.
CANCER	24
The sharp increase in childhood leukemia
over the past 40 years may be due to
environmental exposures.
AIR POLLUTION	38
Learn how kids' respiratory health is
affected by air pollutants.
NEURODEVELOPMENT: GENERAL 28
Exposures to environmental chemicals
before birth and during childhood can
have detrimental effects on learning,
attention, memory, and behavior.
NEURODEVELOPMENT: AUTISM
SPECTRUM DISORDER	30
! he rates of autism have risen in recent
years. Find out the role of prenatal and
parental environmental exposures in
urban or rural settings.
OBESITY	32
Environmental toxicants may play an
important role in obesity. Findings to-date
focus on refining methods for measuring
obesity.
ARSENIC	42
Learn about prenatal exposures to arsenic
and impact on fetal growth. Rice-based
products and drinking water may also be a
source of arsenic exposure.
CONSUMER PRODUCTS
Every day we use a variety of products that
expose us to chemicals that may affect
child development.
CONSUMER PRODUCTS: BPA 44
Found in toys, baby botties, and water
bottles, bisphenol A (BRA) can impact
obesity and reproductive development.
CONSUMER PRODUCTS: PBDEs 48
Used as flame retardants in furniture
and other products, polybrominated
diphenyl ethers (PBDEs) can impair
neurodevelopment.
CONSUMER PRODUCTS:
PHTHALATES	48
Exposure to phthaiates from shampoo,
perfumes, and makeup can affect
neurodevelopment and reproductive
health.
LEAD	50
While lead levels have greatly decreased,
many children are still at risk. Lead
exposure impacts brain structure and
function, contributes to ADHD, and can
diminish school performance.
PESTICIDES	52
Kids are especially susceptible to
pesticides, and exposure before
birth or during childhood may result
in ADHD, lowered IQ, and other
neurodevelopmental disorders.
SECONDHAND TOBACCO SMOKE 58
Learn about how both maternal and
paternal smoking before conception and
during pregnancy can cause asthma,
cancer, and neurodevelopmental effects.

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J
%
HALLMARK
FEATURES
58
COMMUNITY OUTREACH AND
RESEARCH TRANSLATION 60
The Children's Centers have empowered
communities by successfully translating
scientific findings into actionable solutions.
APPENDICES
INDEX
REFERENCES
77
80
CHILDREN'S HEALTH MATTERS 80
EXPOSURE ASSESSMENT
New methods that more precisely
measure the environmental exposures for
both mothers and children.
INTERDISCIPLINARY APPROACHES 66
Examples of how leveraging the unique
expertise of many fields to conduct
research provides evidence to protect our
children.
NEW METHODS AND
TECHNOLOGIES	68
Learn about the pioneering new
approaches and technologies used
to advance the field of children's
environmental health.
POPULATION-BASED STUDIES 70
Studies that start before birth and follow
children up to young adulthood are
invaluable for tracking the effects of
exposures overtime.
RODENT MODELS	72
Examples of how animal models inform
epidemiological studies to help explain
the effects of exposure and reduce the
burden of disease.
SAMPLE REPOSITORY	74
The collection and storage of biological
and environmental samples enable us to
answer questions about exposures over
long periods of time.
64 HEALTH OUTCOMES
81
ENVIRONMENTAL EXPOSURES 90
HALLMARK FEATURES
101
APPENDIX A-LIST
OF EPA REVIEWERS	107
List of EPA staff who provided comments
and recommendations for this report.
APPENDIX B-SUMMARY
OF THE CHILDREN'S GENTERS 108
List of the current and previously
funded Children's Centers, including
environmental exposures and health
outcomes studied by each center.
» V.-i '
' % V ? .'A

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EXECUTIVE SUMMARY
Environmental exposures in the earliest stages of human development—including before birth—influence the occurrence of disease
later in iife. Since 1997, the U.S. Environmental Protection Agency (EPA) and the National Institute of Environmental Health Sciences
(NIEHS) have partnered to investigate new frontiers in the field of children's environmental health research by supporting research
devoted to children's environmental health and disease prevention. EPA funding has been provided under the Science to Achieve
Results (STAR) grant program. STAR funds research on the environmental and public health effects of air quality environmental
changes, water quality and quantity, hazardous waste, toxic substances, and pesticides.
The Children's Environmental Health and Disease
Prevention Research Centers (Children's Centers)
program was established through this unique
partnership, and continues to be successful in
protecting children's health. 46grants have been
awarded to 24 centers through a highly
competitive process.
EPA and NIEHS have together invested more
than $300 million in the Children's Centers
program to expand our knowledge on the
exposures and health outcomes. The partnership
has led to tangible results in communities across the
country.
This impact report highlights some of the progress the
Children's Centers have made toward reducing the
burden of environmentally induced or exacerbated
diseases placed on children.
EXECUTIVE ORDER 13045 — PROTECTION OF CHILDREN FROM ENVIRONMENTAL HEALTH RISKS
Signed in 1997, this Executive Order requires federal agencies to ensure their policies, standards, and programs
account for any disproportionate risks children might experience.14 With this incentive, EPA and NIEHS executed
a memorandum of understanding to jointly fund and oversee a new and impactful research grant program
focused on children's health.
Exemplifying the value of
partnerships between
federal agencies
8

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Approaching the challenge
of studying children's
environmental health
with a unique
perspective
WANT TO
LEARN MORE?
If you are interested
in what makes the
Children's Centers
program unique,
see the Hallmark
Features section.
A Children's Center is not a
pediatric clinic or a physical
building — It is the name
used to describe a research
program investigating the
impact of environmental
exposures on children's
health. Investigators may be
located in one building or at
one university, however many
centers are located across
campuses in one or more
partnering institutions.
Determining what chemical
exposures are toxic to children
requires a variety of research
approaches. Each center
consists of three to four
unique but integrated research
projects related to the center's
theme. Children's Centers
are supported by cores that
provide infrastructure, services,
and resources to the research
projects to help them meet
their long-term goals. Each
center is structured with at
least two cores: one that
coordinates and integrates
center activities, and one that
engages with the community
and translates scientific
findings. A coordinated
interrelationship exists
between the projects and
cores that combine to form
a cohesive center with a
common theme.
Many Children's Centers follow
children from preconception
through childhood, enabling
a deeper understanding of
the effects of environmental
exposures on childhood
diseases. This approach has
also allowed for the collection
of biological samples over
time. These archives of
biological samples serve as a
resource for the future and
provide critical information on
the prenatal and childhood
determinants of adult disease.
The Children's Centers
examine pressing questions
with a wide-angle lens, not
allowing the boundaries of
any particular fieid to restrict,
define, or determine the
array of possible approaches.
They bring together experts
from many fields, including
clinicians, researchers,
engineers, social scientists, and
others. Relying on a diverse set
of disciplines has helped the
centers successfully bridge the
gap between environmental
exposures and health
outcomes.

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Leveraging the expertise of researchers across the country
University of
Washington

University of
California, Davis <
University of California,
San Francisco
University of California,^
Berkeley/Stanford University
€r
University of California,
Berkeley (CERCH)
, University of California,
""""" Berkeley (CIRCLE)
Denver
WANT TO
LEARN MORE?
See Appendix B for
more information
about each
Children's Center.
University of
Southern California
Year Request for
Application (RFA)
Issued
Grants Funded
1997 2000 2003 2005
Approximate Joint
Funding (millions)
$60M
$28M
$52M
$15M

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Fostering a new generation of leaders in children's environmental health
Dartmouth College
\
University
of Michigan	University
(Peterson/	of Michigan
Padmanabhan)	(Israel)
University
of Iowa
University
of Illinois

Columbia^
University"
Cincinnati
Duke
University^
(NICHES)

Emory
University
—Northeastern University
Harvard University
Brown University
Mount Sinai School of Medicine
University of Medicine and
Dentistry of New Jersey
__ The Johns Hopkins
University
Duke University
(SCEDDBO)
KEY:
Open grants
Q Closed grants
^ Colors correspond
to year RFA issued
2009 2009 2012
Formative
$44M
*-+-f
6 6 8
$12M
$62M

I
5
$28M
Totals
8 RFAs
46 grants
$301M
11

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Leading the field in research that
improves the quality of life for
children and adults
The Children's Centers have
transformed the field of
children's environmental
health. They have
heightened awareness of
children's environmental
health—both nationally
and internationally—and
have helped establish it
as a distinct field of study.
Research from the centers
has led to new detection,
treatment, and prevention
strategies for diseases related
to environmental exposures.
Children's Centers
research has
identified the critical
role environmental
toxicants play in
the development
of asthma, obesity,
ADHD, cancer,
autism, and other
childhood illnesses
that may set the
trajectory of health
throughout adult life.
The centers have led the way
in clarifying the relationship
between exposures in the
earliest stages of human
development—including
before birth—and the
occurrence of disease later in
life. Improving understanding
of the developmental origins
of health and disease is
critical for developing effective
interventions to reduce health
risks and improve quality of
life for children and adults.
WANT TO
LEARN MORE?
If you are interested
in a specific disease,
see the Health
Outcomes section
If you are interested
in a specific
chemical, see the
Environmental
Exposures section
Children's Centers Publications by Year (as ofjune 2017)
CD
-Q
E
200
150
100
50
198
181 183
194 193
ooa>o^f\ico^riocor^co
0)0)000000000
0)0)000000000
T-T-(NCMCMCMCNCNCNCNCN
2,544 publications,
includingjournal articles and
book chapters.
141 publications per year,
on average (excluding 1998).
Year
Through their groundbreaking work, the Children's Centers have pushed the boundaries of clinical, field,
and laboratory-based research. The research has been disseminated through thousands of publications in
diverse and peer-reviewed journals. The research findings lay a critical foundation for reducing health risks and
improving quality of life for children and adults.
12

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Serving communities in ways
that help protect children
and pregnant women
WANT TO
LEARN MORE?
Ifyou are interested
in the community
outreach and
research translation
efforts by the
Children's Centers,
see the Hallmark
Features section.
2,300 Facebook posts
Tweets
-*b3sed orrajyofi :IP 7 Altniatric gnalyats of 1,87? CJcjdrsn^ 'CerttsB-'Pttbl.icati'ons
13
ill
NBC
®CBS
1,400 news media stories
Many times, scientific findings
and research results are
complex and difficult to
understand. Empowered by
Children's Centers program
requirements"5 to translate
and apply research findings to
protect children, the Children's
Centers successfully translate
and communicate scientific
findings into actionable
solutions. The centers provide
the public, community
organizations, healthcare
professionals, decision makers,
and others with practical
information about the science
linking the environment to
children's health.
Innovative partnerships
between researchers and
the community help drive
research design, lead to
practical interventions, and
create culturally-appropriate
communication materials.
Through their efforts, the
centers empower community
members to participate in
planning, implementing, and
evaluating interventions and
public health strategies for
healthier children, families, and
future generations.
Research from the Children's
Centers has reached
thousands of people across
the world through various
forms of media*

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Continuing to transform the landscape
The Children's Centers are integral to both EPA and NIEHS'
research programs. The centers are one of several commitments
to foster a healthy environment for children. They have advanced
our understanding of the critical role environmental toxicants
play in the development of childhood illnesses that may set the
trajectory of health throughout adult life.
While EPA and NIEHS have together invested more than $300
million in the Children's Centers program to better understand
the impact of the environment on children's health, there is still
much to learn. The relationships between many environmental
exposure and health outcomes remain unexplored. More data is
needed to reduce or eliminate any uncertainties in associations
between environmental exposures and health outcomes.
The work of the Children's Centers
program has identified the need for more
feasible, simple strategies to prevent
environmental exposures and reduce the
burden of disease in children.
Future efforts to protect children's health will require
collaboration with communities, health professionals, and local,
state, and federal governments. The strong relationships that the
centers have established will benefit researchers and members
of the community in the future.
The future of children's environmental health relies on research
that expands knowledge, reduces uncertainty, and furthers
collaboration.
14

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of children's environmental health
k
i
The Children's
Centers
research
program
addresses
a broad range
of key issues
by:
Stimulating
new and
expanding
existing
research
on the
environmental
determinants of
children's health
and the biological
mechanisms that
impact health and
development.
Using an inter-
disciplinary
approach
to understand
the persistent
developmental
effects of chemicals
and other
environmental
exposures from
preconception
through childhood
and adolescence.
Enhancing
communication
and accelerating
translation of
research findings
into applied
intervention
and prevention
methods.
15

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COMMONLY USED ACRONYMS
ADHD - Attention-Deficit Hyperactivity
Disorder
ASD - Autism Spectrum Disorder
BPA- Bisphenol A
EDCs - Endocrine Disrupting Chemicals
IPM - Integrated Pest Management	PCBs - Polychlorinated Biphenyls
N02 - Nitrogen Dioxide	PM - Particulate Matter
OP - Organophosphate	STS - Secondhand Tobacco Smoke
PBDEs - Polybrominated Diphenyl Ethers	UC - University of California
PAHs - Polycyclic Aromatic Hydrocarbons	|Jg/dL - Micrograms per deciliter
CENTER NAMES AND AFFILIATIONS
Brown University - Formative Center for the Evaluation of
Environmental Impacts on Fetal Development*
Cincinnati - Center for the Study of Prevalent Neurotoxicants in
Children
Columbia University - Columbia Center for Children's
Environmental Health
Dartmouth College - Children's Environmental Health and
Disease Prevention Research Center at Dartmouth
Denver - Environmental Determinants of Airway Disease in
Children
Emory University - Emory University's Center for Children's
Environmental Health
Duke University (NICHES) - Center for Study of
Neurodevelopment and Improving Children's Health Following
Environmental Tobacco Smoke Exposure
Duke University (SCEDDBO) - Southern Center on
Environmentally-Driven Disparities in Birth Outcomes*
Harvard University - Metal Mixtures and Children's Health*
Mount Sinai School of Medicine - Inner City Toxicants, Child
Growth, and Development
Northeastern University - Center for Research on Early
Childhood Exposure and Development in Puerto Rico
The Johns Hopkins University - Center for the Study of
Childhood Asthma in the Urban Environment
* Specific findings from these Centers are not discussed in this report
University of California, Berkeley (CERCH) - Center for
Environmental Research and Children's Health
University of California, Berkeley (CIRCLE) - Center for
Integrative Research on Childhood Leukemia and the Environment
University of California, Berkeley/Stanford University-
Berkeley/Stanford Children's Environmental Health Center
University of California, Davis - Center for Children's
Environmental Factors in the Etiology of Autism
University of California, San Francisco - Pregnancy Exposures
to Environmental Chemicals Children's Center
University of Illinois - Novel Methods to Assess Effects of
Chemicals on Child Development
University of Iowa - Children's Environmental Airway Disease
Center
University of Medicine and Dentistry of New Jersey - Center
for Childhood Neurotoxicology and Assessment
University of Michigan (Peterson/Padmanabhan) -
Lifecourse Exposures and Diet: Epigenetics, Maturation and
Metabolic Syndrome
University of Michigan (Israel) - Michigan Center for the
Environment and Children's Health*
University of Southern California - Southern California
Children's Environmental Health Center
University of Washington - Center for Child Environmental
Health Risks Research
16

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READING GUIDE
The Children's Centers have led the way in demonstrating
many of the links between environmental exposures and
health outcomes. This report outlines some of the important
contributions the Children's Centers have made to the field
of children's environmental health.
It is often challenging to neatly categorize research findings
and you will notice an overlap between the topic areas. For
example, findings about air pollution may also be found in
the topic area about asthma. To assist readers, an index has
been provided that lists the various places where a topic is
mentioned.
Are you interested in learning more about a specific disease,
like autism or cancer? Or intrigued about how children
may be exposed to environmental toxins, like BPA or lead?
You will see the report is split into Health Outcomes and
Environmental Exposures. Within each of these sections,
the report is organized into topic areas that the Children's
Centers have focused on since the inception of the program.
Each topic area includes a brief background, a summary
of scientific findings, and examples of impacts in the
community or in decision making. Each of these sections can
be identified by text box color and location on the topic page.
Interested
in scientific
research?
Read the research findings boxes
at the bottom of each page. These
findings are linked to the publication
abstracts to help you gain a
greater depth of scientific
understanding.
Need an overview of
children's environmental
health?
Focus on the top half of each topic
area page, which provides general
information.
Interested in impacts in
communities?
Read the Impact on Community boxes at
the bottom of some of the topic area pages.
Also read the Community Outreach and
Research Translation topic area in the
Hallmark Features section.
Want to know
what makes the
Children's Centers so
successful?
Read the Hallmark Features
section to learn about the unique
characteristics that have
facilitated the program's
success.
17

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Infants and children are more vulnerable than adults to the negative effects
of environmental exposures. The rapid growth and development that occurs
in utero and during infancy, childhood, and adolescence makes children
especially susceptible to damage. In fact, exposures throughout childhood can
have lifelong effects on health.
Many factors contribute to children's health, including genetics, nutrition, and
exercise, among others. The adverse health consequences of environmental
exposures may occur along with other risk factors, and it is often difficult to
determine the extent that the environment contributes to children's health.
The following pages present research from the Children's Centers on
increasing rates of common chronic illnesses and the role of environmental
exposures.

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ASTHMA
20
BIRTH OUTCOMES
22
CANCER
24
IMMUNE FUNCTION
26
NEURODEVELOPMENT
28
NEUROOEVELOPMENT: AUTISM SPECTRUM DISORDER
30
OBESITY
32
REPRODUCTIVE DEVELOPMENT
35

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$56 billion:
Yearly cost of
asthma in the U.S
(all ages).6
BACKGROUND
In the U.S., 6.2 million children have asthma.1 Exposure to environmental chemicals
can worsen asthma symptoms and can reduce ability to control those symptoms.2
Asthma affects people of all ages, but most often starts during childhood; it is one of
the top reasons that children miss school.3 Asthma is a chronic disease, and symptoms
include wheezing, breathlessness, coughing, and chest tightness.4 These symptoms
can be controlled by medication and by avoiding triggers. However, certain things such
as air pollution, mold, and secondhand smoke can worsen symptoms*5 Since 1980,
the number of children with asthma and the severity of symptoms have risen sharply,
putting tremendous burden on families and making this issue critically important to
communities.4
Exposure to air pollution is associated with an increased risk of asthma.7 Traffic-related air pollution (TRAP) includes polycyclic
aromatic hydrocarbons (PAHs), particulate matter (PM), nitrogen dioxide (N0o), and ozone. The levels of TRAP are high near
roadways and decline markedly as you move further away. Children who live, attend school, or play near major roadways are
more susceptible to asthma.
Asthma risk increased in children who lived closer to major freeways, even those with no family history of asthma.as
New onset asthma in primary school children could be associated with local TRAP near homes and schools.7
Wheezing increased in children with asthma after ambient exposure to PAHs.l!
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Increased asthma symptoms and reduced lung function were associated with exposures to ambient PM and ozone in
children with moderate to severe asthma.11
20

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When I have an
asthma attack,
I feei like a fish
with no water.
Jesse, 5 years old.8
The Children's Centers have investigated the causes of asthma so that children can maintain a normal quality of life. Both
outdoor and indoor air pollution can pose a risk to children whether they live in inner cities or rural communities.
The Children's Centers research has helped clarify the relationship between air pollution and asthma. The research has also
found links between asthma and exposures to other chemicals, such as bisphenol A (BPA) and pesticides. Researchers learned
that timing matters too. Multiple windows of exposure, including during prenatal and postnatal development,
can make a difference when it comes to asthma. Research from the Children's Centers help support an improved
understanding of asthma and has helped children and their families better manage this chronic disease. The research has also
led to simple, feasible interventions to reduce the severity of asthma symptoms. For example, The Johns Hopkins University
Children's Center used portable high efficiency particulate air (HEPA) filters in the homes of children who lived with a smoker,
resulting in 33 fewer days per year with asthma symptoms,13 The Children's Centers research is now moving toward exploring
the links between asthma and other emerging factors, including obesity and immune function.
Children living in rural areas experience different environmental exposures than those living in urban areas. Children in
agricultural settings often live, play, and work on farms, with children as young as 5 years old participating in farm chores.
The study observed that children in this region were mainly exposed to organic dusts, such as grain and cotton dusts,
or dusts generated in dairy barns. Other exposures that influenced asthma development were animai-derived proteins,
common allergens, and low concentrations of irritants. The asthma prevalence in rural children rivaled that of children in
large Midwestern cities. These results counter the preconceived idea that rural life has a protective effect for childhood
asthma.lS
Recent studies found consistent associations between childhood organophosphate (OP) pesticide exposure, increased
asthma symptoms, and reduced lung function in children This finding is consistent with known acute effects of OP
pesticide exposure and raises concerns about health impacts in agricultural areas^15 Researchers also found strong
associations between sulfur use in agriculture and poorer respiratory health. Sulfur, which is of low toxicity and approved
for conventional and organic agriculture, is a respiratory irritant and the most heavily used pesticide in California.0
Recent studies about the ways air pollution may exacerbate asthma focused on a particular group of immune cells, called	c
T cells, that are important in controlling immune responses for iSthrria.®70 Researchers identified how PAHs impaired	2 £
T celi function; in children with asthma, impaired T cell function is associated with increased asthma morbidity and	| %
decreased lung function.18Additionally, chronic exposures to ambient PAHs cause epigenetic changes that can suppress	3. s-
immune system regulation in children with asthma.21
21

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In the U.S., more
than 1 in 10
babies are
born preterm.26
BACKGROUND
The physical and emotional effects of birth outcomes, such as preterm birth, low
birth weight, and structural birth defects, can be overwhelming and the medical
costs staggering.22 In some cases, prenatal exposure to environmental chemicals
may be the cause.®3 Many adult diseases are also believed to have their origins in
fetal life* For example, a newborn with low birth weight (less than 5.5 pounds) has
an increased risk of health problems in childhood and adulthood.28These infants
also have an increased chance of getting sick in the first six days of life, developing
infections, and suffering from long-term problems including delayed motor and social
development or learning disabilities.25
• • • ^ • • •
|T -n Maternal exposure to air pollution appears to substantially increase the risk of early preterm birth (less than 27 weeks
% | gestation). These findings are from one of the largest studies of these associations and have extended the understanding
u s of the effects of air pollution,®2®
Maternal exposure to ozone may be associated with reduced birth weight in newborns^The 2013 EPA Integrated
Science Assessment for ozone reports that, of all studies considered, the University of Southern California Children's
Center provided the strongest evidence for a relationship between ozone exposure and birth weights-
Maternal exposure to phthalates during pregnancy is associated with decreased fetai growth.32These findings were
consistent across different growth parameters (head circumference, femur length, fetal weight) and by fetai sex. Maternal
phthalate exposure during early pregnancy is also related to birth size and gestational agmJa
p	Studies suggest that pesticide exposure is higher for resident agricultural families and agricultural workers;* Prenatal
| u	exposure to organophosphate (OP) pesticides was associated with preterm birth in a population of iow-income women
™ S	living in an agricultural community in California. Increased pesticide exposure later in pregnancy was more strongly
3	associated with shortened gestation.?*
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"You can, as a
pregnant woman,
decide not to
smoke or not to
drink, but you
can't avoid the air
that you breathe."
- Dr. Linda McCauley,
Co-Director; Emory
University Children's Center.
Adverse birth outcomes can negatively impact health during childhood and adulthood. The Children's Centers research has
identified links between preterm birth, air pollution, and pesticides. Researchers also found that exposure to arsenic, ozone,
phthalates, and PBDEs contributed to lower birthweight. The centers have engaged with communities to address
concerns about how the environment may be impacting pregnancy. The Children's Centers continue to improve the
understanding of how the environmental contributes to birth outcomes in order to prevent exposures and improve children's
quality of life.
Prenatal development is a period marked by rapid growth and is therefore highly sensitive to the effects of toxic
exposures. Evidence suggests that fetal growth is an important predictor of adult health.36 Since arsenic can cross the
placental barrier, low level exposures may affect fetal growth.® Prenatal arsenic exposure was associated with decreased
head circumference of newborns and decreased birth weight for baby girls born to overweight or obese mothers.38®
Flame-retardant chemicals called polybrominated diphenyl ethers (PBDEs) are used in furniture, vehicles, and	_ £
consumer electronics. Prenatal exposure to PBDEs was associated with decreased birth weight in a population of	£ ®
low-income women living in California. These findings are consistent with other recent studies. This was the first	£ |
prospective study to examine fetai growth independent of gestational age at birth.3®	•<
IMPACT ON COMMUNITIES
The Emory University Children's Center created a short documentary to increase awareness of prenatal environmental
exposures and pregnancy outcomes among African American women living in metro Atlanta* The center partnered with its
Stakeholder Advisory Board, which includes mothers, grassroots and non-profit organizations, community and environment
advocates, breastfeeding counselors, an urban farmer, and state government representatives. The video is helping to raise
awareness of food and household hazards within the community and is shared on social media.
23

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More than 10,000
U.S. children under
age 15 will be
diagnosed with
cancer in 2017.
Tragically, 1,190 of
these children will not
survive.46
BACKGROUND
Cancer is the second leading cause of death among children between ages 1 and 14
years old.4' Leukemia, cancer of the white blood cells, is the most common childhood
cancer,42 The number of children diagnosed with leukemia has increased by about 35
percent over the past 40 years, especially among Latino children as shown in recent
studies in the U.S.43 u Part of this increase is likely due to changes in patterns of
exposure to chemicals introduced into a child's environment, alone or in combination
with genetic susceptibility.?3'46 Cancer survivors can develop health problems after
receiving treatment, known as late complications, but children are of particular concern
because cancer treatment during childhood can lead to significant lasting physical,
cognitive, and psychological effects*It is therefore critical to understand what causes
leukemia in children in order to develop prevention strategies This way, not only is the
incidence of disease reduced, but aiso the iifeiong impacts for children and their families.
Because the majority of childhood leukemias occurs before age 5, it is important to understand the most vulnerable
windows of a child's exposure to harmful chemicals.5® For example, paternal occupational chemical exposures before
and after the child's birth are associated with risk of childhood leukemia.
Ol ^
5 3 Latino fathers exposed to known or possible carcinogens such as pesticides, polycyclic aromatic hydrocarbons (PAHs)
¦£ u
S ~ in combustion exhaust, and chlorinated hydrocarbons at work were more likely to have children with leukemia.^-«
=> Chlorinated hydrocarbons are volatile and cannot be tracked back home; thus, paternal exposure during preconception
is the most likely susceptible window of exposure.®'45 In contrast, pesticides and PAHs are semi-volatile and can be
transported from work back home; thus, the susceptible windows of exposure related to paternal occupation may be
before and after the child's birth.48-43
24

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Research from the UC Berkeley (CIRCLE) Children's Center has made important strides in uncovering associations
between leukemia and exposure to tobacco smoke, pesticides, paint, organic solvents, polychlorinated biphenyls
(PCBs), polybrominated diphenyl ethers (PBDEs), and PAHs. The UC Berkeley (CIRCLE) Children's Center's findings on
chemical and dietary factors of childhood leukemia provide the scientific basis for prenatal and postnatal prevention efforts
directed toward the most vulnerable populations, such as Latino communities exposed to high levels of pesticides and organic
solvents.^This center also investigates the interplay between genetic, immune, and chemical factors to better understand how
chemical exposures may cause leukemia. Researchers are educating clinicians, public health professionals, and parents about
the importance of environmental risk factors for childhood ieukemia. The long-term goai is to reduce both the incidence of this
disease and of neurodeveiopmental, respiratory, and other diseases caused by the same environmental exposures.
COLLABORATION
Research to identify risk factors for leukemia requires muiti-disciplinary and muiti-institutionai efforts. In partnership with
researchers from all over the world and the International Agency for Research on Cancer, the UC Berkeley (CIRCLE) Children's
Center has supported the expansion of the Childhood Leukemia International Consortium (CLIC). CLIC has gathered
information from 35 studies in 18 countries on 40,000 children with leukemia and 400,000 controls. With this unparalleled,
large number of participating children, CLIC has identified associations of childhood leukemia with multiple chemicals, immune
and infectious factors, and fetal growth. (CIRCLE) and CLIC researchers also reported that a healthy maternal diet and vitamin
supplementation at the time of conception and during pregnancy reduce the risk of childhood leukemia.3® The evidence-
based methodology used in CLIC provides a strong basis to translate research into action that wiii prevent childhood leukemia.
Exposure to PCBs, PBDEs, and PAHs are potential new risk factors for childhood leukemia.51'66 Alternative assessment methods
developed by the Children's Centers made the discovery of these novei risk factors possible.
Traditional methods for assessing exposure, such as interviews and questionnaires, yield limited results due to their lack
of specificity and possible reporting biases. Researchers developed a novel assessment method: collecting dust samples ¦= n
— uj
from households and analyzing them for levels of persistent organic pollutants. They compared the chemical levels in	of.
m ff
the dust samples to chemical levels in children's and mothers' blood samples. They demonstrated that the mothers and " 5"
children living in the most highly contaminated households had the highest burden of these chemicals in their bodies.®'-®
25

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Approximately 30%
of people worldwide
will suffer from atopic
disease at some point
in their lives.®
BACKGROUND
Prenatal and early life environmental exposures can interfere with the function
and regulation of the immune system, which can have harmful effects later in life
including neurodevelopmental disorders and cancer.59 The immune and nervous
systems are tightly linked, and there is growing evidence that disturbances in one
can have serious consequences for the other. Disruptions to the immune system
contribute to autism spectrum disorder (ASD) and other brain development
disorders, including lower IQ, problems in social behavior, and poor motor skills.?8
Several genes linked to ASD also have critical roles in immune signaling, activation,
and regulation e Dysregulation of the immune system has also been linked to
other health outcomes, such as childhood leukemia and atopic disease* Atopic
diseases are a group of diseases linked by a shared underlying problem with the
immune system and include asthma, allergic rhinitis, and atopic dermatitis (eczema).
Rates of atopic diseases have also rapidly increased in prevalence, possibly due to
environmentally-mediated epigenetic changes,6®
Cytokines are proteins that control the immune response and influence the nervous system. Individuals with diseases such as
ASD and leukemia and their family members are more likely to experience altered cytokine expression
•	Exposure to PBDEs was linked to asthma and high inflammatory cytokine levels in children with ASD;64
•	The newborn blood spots of children who were later diagnosed with ASD showed increased inflammatory cytokines
IL-1 p and IL-4. Early life cytokine production can possibly predict ASD diagnosis.^
•	Children with ASD had increased levels of pro-inflammatory cytokines and chemokines. High levels of these proteins
during development may disrupt the immune system.®*0'
> • Preliminary results suggest that exposure to polychlorinated biphenyls (PCBs) is associated with decreased cytokine
| j IL-10 levels, potentially linking this chemical to both leukemia risk and loss of immune regulation,®4 Children diagnosed
® ~ with leukemia have decreased levels of the immunoregulatory cytokine IL-10 at birth, that may later result in more
severe responses to common childhood infections.70'1,1
26

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Exposures to harmful chemicals during prenatal and early childhood development can disrupt normal function of the
immune system. Children's Centers research suggests that disturbances in the immune system may play a role
in neurodevelopmental disorders and ASD. Immune dysregulation can also make children more susceptible
to atopic diseases such as asthma and allergies, and severely elevate their responses to common childhood
infections. Children's Centers research shows that childhood cancers like leukemia may also be associated with toxic
environmental exposures that act on the immune system. The Children's Centers have intensively studied the role of individual
chemicals and their influence on health through changes to the immune system, but there is still much to learn.
Maternal immune dysfunction and prenatal environmental exposures can result in ASD and metabolic conditions later
in life. Mothers of children with ASD have unique autoantibodies that can bind to neurons and affect behavior,75^3 The
presence of these ASD-specific autoantibodies in mothers has been linked to decreased immune regulation, cMET
polymorphisms, and increased metabolic conditions such as diabetes*
Immune cells called T cells are key mediators of the adaptive immune system and play critical roles in modulating atopic
responses, such as inflammation. Because of this, T cells are a possible target for therapeutic interventions in atopic
disorders. The centers have worked to determine the molecular mechanisms where immune dysregulation leads to
atopic disease in children exposed to high levels of ambient air pollutants.
•	Exposure to air pollution was linked to changes in the DNA of immune cells. These changes may lead to impaired
cellular function.18
¦ Exposure to air pollution, including polycyciic aromatic hydrocarbons (PAHs), was associated with decreased regulatory
T cell function, increased asthma severity, and lower lung function in children with asthma.1®
•	Exposure to air pollution resulted in epigenetic changes that were sustained over time,®
•	The damage to the immune system was more pronounced in children with asthma or rhinitis than in children without
atopic disease.1®
C
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Qi
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27

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I he brain reaches
approximately 90%
of its adult size by
BACKGROUND
At birth, a baby has formed almost all of its brain cells?® Exposure to chemicals
such as mercury, lead, arsenic, and pesticides can have negative effects on brain
development, leading to cognitive delay, attention-deficit hyperactivity disorder
(ADHD), lower IQ, higher rates of anxiety and depression, behavior and learning
disorders, reduced self-regulatory capacities, and shortened attention span/*
® Currently, neurodevelopmental disorders affect 10 to 15 percent of children
born annually, and rates of certain disorders have been increasing over the
past 40 years.89'® Not only can prenatal exposures to toxins increase the risk of
neurodevelopmental disorders at birth, but they can also lead to disorders later in
childhood,;®1
Prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) can have negative effects on cognition and
behavior in childhood. PAHs are widespread in urban areas largely as a result of fossil fuel combustion, specifically diesel
fuel exhaust. The Columbia University Children's Center cohort of mothers and children in New York City was the first
human study to examine the effects of prenatal exposure to PAHs on chiid development. Associations between prenatal
PAH exposure and adverse cognitive and behavioral outcomes include:
•	Increased likelihood to exhibit signs of cognitive developmental delay at 3 years old. These results suggest that more
highly exposed children are potentially at risk for performance deficits in the early school years?
•	Lower full-scale and verbal IQ test scores at 5 years old.7®
•	Increased symptoms of anxiety, depression, and attention problems at 6 to 7 years olds,®
•	Slower information processing speed, increased aggression, and other behavioral self-control problems, and increased
ADHD symptoms at age 7 to 9 years old,®'
•	Increased behavioral problems associated with ADHD at age 9. This is the first study to report associations between
individual measures of early-life exposure to PAHs and ADHD behavior problems.9'
•	Long-lasting effects on self-regulatory capacities across early and middle childhood. These deficits point to emerging
social problems with real-world consequences for high-risk adolescent behaviors,®
28

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The Children's Centers are exploring associations between brain development and environmental toxicants such as lead,
pesticides, phthaiates, PAHs, bisphenol A (BPA), and polybrominated diphenyl ethers (PBDEs). Prenatal exposures to
pollutants have shown a relationship to adverse cognitive and behavioral outcomes, demonstrating links to:
ADHD, reduced IQ, lessened self-regulatory capacities, anxiety, depression, attention problems, lower memory
function, and structural changes to the brain. Researchers have engaged with parents, childcare providers, and decision
makers to encourage changes that reduce exposures and improve children's neurodevelopment. Children's Centers findings
have helped develop public health policy and interventions aimed at protecting pregnant women and their babies from toxic
environmental exposures. Their findings support the need for additional action.
Phthaiates are commonly used in plastics and may affect neurodevelopment in children because they can be released
into indoor air and attach to dust particles, that people breathe.
•	Phthaiate concentrations in indoor dust were higher in houses of children with developmental delay compared to
children without developmental delay:93
•	Among boys with autism spectrum disorder and developmental delay, greater hyperactivity-impulsivity and inattention were
associated with higher phthaiate concentrations in indoor dust.m
¦ Among children without any developmental delays, impairments in several adaptive skills such as ability to follow directions,
written abilities, and language skills were associated with higher phthaiate concentrations in indoor dust.92
Prenatal exposure to chlorpyrifos can interfere with children's brain development. Chlorpyrifos is a pesticide still widely
used in agriculture, however, in 2000 it was banned for almost all homeowner use.®1n a 1998 sample of pregnant
women In New York City, detectable ievels of chlorpyrifos were found in all indoor air samples and 70 percent of umbiiicai
cord blood samples:84'85 Since the ban, levels in indoor air and blood samples have decreased significantly in study
participants. Children exposed to higher levels of chlorpyrifos before birth displayed adverse cognitive and behavioral BIB
outcomes compared to children exposed to lower levels, including:
•	Significantly lower scores on mentai development tests and increased attention problems and symptoms of ADHD at 3 1-B
years old.8®	H|B
•	Lower full scale IQ and working memory test scores at 7 years old#6 The effect on working memory was more
pronounced in boys than in girls with similar chlorpyrifos exposures.69'
•	Structural changes in the brain in regions that serve attention, receptive language, social cognition, emotion, and
inhibitory control, and are consistent with deficits in IQ.®8
29

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Caring for a child with
ASD costs about
$17,000 more per
year than caring for
a child without ASD.99
BACKGROUND
Autism spectrum disorder (ASD) includes a wide range of symptoms and levels of
disability characterized by challenges with social skills, repetitive behaviors, speech,
and non-verbal communication, along with unique strengths and differences,93 ASD
was previously thought to be mainly due to genetics, however it is now understood that
environmental factors play an important role; the estimated genetic contribution to ASD
has decreased from 90 percent to 38-60 percent®1* Approximately 1 in 68 8-year-old
children have ASD, and it is even more common iri boys (1 in 42) than in girls (1 in 189).
Rates of ASD have been steadily increasing since 2002.®"® Whiie several factors may
contribute to the observed rise in ASD, including changes in the diagnostic criteria, an
earlier age of diagnosis, and inclusion of milder cases, these could not account for the
full extent of the increase,91
Research on the relationship between traffic-related air pollution (TRAP) and ASD suggest that iate pregnancy and early
life are critical windows of exposure. Measuring residential distance to a major roadway is often used as a marker of
TRAP.
• For mothers who lived near a freeway during pregnancy, the risk of having a child with ASD doubled.™
Children who were exposed to higher levels of TRAP in utero and in the first year of life were more likely to develop
asd.«
Parental environmental and occupational exposures have been linked to ASD and developmental delay.
•	Children were at higher risk for developing ASD if their parents were exposed to lacquer, varnish, and xylene at their
jobs.®
•	Children were at greater risk for ASD and developmental delay if their mothers were residing near pyrethroids
insecticide applications just before conception or during the third trimester.m
•	Children were 60 percent more likely to develop ASD if their mothers resided near agricultural fields where
organophosphate (OP) pesticides were applied during their pregnancy. The association was strongest for third-
trimester exposures and second-trimester chlorpyrifos applications.1®
30

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i> I
f j
"We hope to identify
chemical exposures, maybe
not for every autistic child,
but for subsets of children
that are particularly
sensitive to chemicals. If
one could identify those
chemicals and remove or
reduce their prevalence
in the environments in
which children live, one
would be in a position to
say that we've reduced the
prevalence of autism."
- Dr. Isaac Pessah, Director,
UC Davis Children's Center.
The Children's Centers have launched the field of research on environmental contributions to ASD. The centers have made
significant advances both in identifying modifiable risk factors and in generating evidence for several mechanistic pathways.
Researchers have identified potential links between air pollution, pesticides, occupational exposures, phthalates,
and risk of ASD. The Children's Centers discovered the first gene-by-environment Interactions in the development of ASD.
Research at the UC Davis Children's Center led to the development of a biomarker test for early risk of having a child with
autism. This technology is now being developed into a commercial test. Thus, since the inception of the Children's Centers
program, the landscape has changed; rigorous research is now being published at a steady and increasing rate, pointing to
avenues for preventive strategies and treatment options.
r i
/CHARGE\
\„/
The UC Davis Children's Center
initiated the CHARGE (The
CHiidhood Autism Risks from
Genes and Environment) Study,
a case-control study of children
with and without ASD. CHARGE
is the first comprehensive study
of environmental causes and
risk factors for ASD. Since 2003, the study has enrolled
California preschool students with and without autism
and other developmental delays. Researchers collected
information about chemicals in the environments of these
children before and after birth, and assessed children
for their stage of social, intellectual, and behavioral
development. This study was the first to identify an
interaction between genes and the environment that
contributes to ASD.
Research has uncovered that interaction
between genes and the environment may
contribute to ASD. A functional promoter
variant in the MET receptor tyrosine kinase
gene, that regulates aspects of brain
development, might interact with air pollution
to increase the risk of ASD. Children with
high air pollutant exposures and the variant
MET genotype were at increased risk of ASD
compared to children who had neither high
air pollutant exposures nor the variant MET
genotype. Subsequent animal toxicological
research strengthened the causal inference
and indicated a possible mechanism for air
pollution effects.1®4
31

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Obesity affects 17%
of U.S. children 2 to 19
years old, However, the
rates of obesity are higher
in certain racial/ethnic
groups.112
BACKGROUND
Childhood obesity remains a public health concern. While diet and limited
physical activity are clear contributors to obesity, other factors, such as genetics
and environmental toxicants, may play an important nale^110Although rates
of childhood obesity have been declining in certain groups, rates are steadily
increasing among others, including Hispanic girls and African American boys.
Individuals who are obese as children are more likely to be obese as adults; they
are also at a higher risk of developing debilitating and costly chronic diseases later
in life, including heart disease, type 2 diabetes, stroke, osteoarthritis, and cancer;111
Endocrine disrupting chemicals (EDCs), such as bisphenol A (BRA) and
phthalates, can interfere with the body's natural hormones. Exposure to
EDCs during critical periods of development may play a role in childhood
obesity and type 2 diabetes by disrupting metabolic homeostasis.1® '*'
Prenatal exposure to EDCs was associated with several biomarkers of
metabolic homeostasis, including leptin, iipids and insuiin-like growth
factor 1, and measures of insulin secretion and resistance in children 8 to
14 years old.
Obesity Rates in the U.S.
22%
i_i- • African ......
Hispanic American White
Among children with asthma, being overweight or obese increased susceptibility to indoor air pollutants fine particulate
matter (PM.,5) and nitrogen dioxide (NO.,). These findings suggest that interventions aimed at weight loss might reduce
asthma symptoms in response to air pollution. Additionally, interventions aimed at reducing indoor pollutant levels might
be particularly beneficial for overweight children.'3^
While laboratory studies on rodents have shown a link between air pollution, fat distribution, and insulin resistance, few
human studies have investigated whether air pollution contributes to obesity in childhood. Studies from the University
of Southern California Children's Center were among the first epidemiological studies to indicate that exposure to
air pollution is related to body mass index (BMI) in children. Near-roadway air pollution, secondhand tobacco smoke,
maternal smoking during pregnancy, and prenatal exposure to PAIHs were all associated with increased BMI in
children..''1®11113
32

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"We want to bring
another piece into
the puzzle of healthy
environments, and we
sincerely hope that our
research will inform
better interventions
that reduce the risk of
obesity in children."
- Dr. Karen Peterson, Director,
University of Michigan Children's
Center.
Center research findings have demonstrated that prenatal and early childhood exposures to BPA, phthalates, air
pollution, and secondhand smoke lead to obesity in childhood, that persists into adulthood. The Children's Centers
are advancing how we think about measuring obesity. Since traditional indicators may not be sufficient in the investigation of
health effects related to obesity, several Children's Centers are assessing alternative methods of body composition. Working in
the community, researchers have engaged parents, families, and teachers to encourage lifestyle changes to reduce obesity and
improve children's health across the country.
Traditional measurements, such as BMI, may not be sufficiently sensitive to study body composition in children.
Alternative methods are needed to more accurately study the effects of environmental exposures on obesity and
metabolic health. For example, results show that prenatal exposure to BPA was associated with fat mass index, percent
body fat, and waist circumference, but not with BMI.These findings confirm that traditional indicators that consider
only height and weight may not be sufficient in accurately assessing children's health.
IMPACT ON COMMUNITIES
More than 200 community members,
environmental health and green space advocates,
health practitioners, urban planners, and obesity
prevention organizations participated in the
2017 "Parks, Pollution & Obesity: Going Beyond
Exercise and Eating" meeting. Hosted by the
University of Southern California Children's
Center, the event advanced a community-
oriented discussion of land-use strategies that
maximize the benefits of physical activity and
minimize potential exposures to air pollution,¦
The Children's Centers have been on the forefront of
using alternative methods to measure obesity both
in children and in pregnant women The University of
Michigan and University of Illinois Children's Centers are
using bioelectrical impedance, which determines the flow
of an electric current through body tissues to estimate fat
free body mass. This is especially useful when measuring
obesity in pregnant women, when traditional methods
such as waist and hip circumference do not apply. The
Cincinnati and the University of Michigan Children's
Centers are utilizing dual energy x-ray absorptiometry
scans to measure bone mineral density and also fat mass
and distribution using iow levels of x-ray technology.
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33

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9

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BACKGROUND
Adolescents may be particularly vulnerable to the effects of toxic chemicals because of the rapid development that occurs
during puberty. Adolescence is also an important period of life when children acquire reproductive capability. Evidence
suggests that environmental exposures to chemicals such as phthalates can affect the timing of puberty. Children who reach
puberty at an early age have been found to be at increased risk of psychological and social issues during adolescence and
metabolic, cardiovascular, and endocrine-related diseases and cancers in adulthood.121'122
Children prenatally exposed to higher levels of phthalates began puberty either earlier or later, depending on sex,
compared to those prenatally exposed to lower levels of phthalates.
•	Girls 8 to 14 years old with higher prenatal phthaiate exposures had alterations in sex hormone levels that indicate
earlier pubertal development. Girls also developed pubic hair and started menstruation earlier when prenatal
phthaiate metabolites were higher.'14!*
•	Boys 8 to 14 years old with higher prenatal phthaiate exposures had alterations in sex hormone levels that indicate
later pubertal development. Boys also developed pubic hair iater and had lower mature testicular volume when
prenatal phthaiate metabolites were higher.1^®
Girls exposed to higher levels of phthalates at an early age developed breasts and pubic hair at a later age than girls
who were exposed to lower levels of phthalates.1*These findings are from a long-term study that measured levels of
phthaiate metabolites in urine samples from girls 6 to 8 years old, continuing until they are 12 to 14 years old.
Girls prenatally exposed to polybrominated diphenyl ethers (PBDEs) reached puberty earlier than girls not exposed.	- q
However, boys prenatally exposed to PBDEs reached puberty later than those not exposed. These results suggest	g %
I rt>
opposite pubertal effects in girls and boys.13*	w ®
35

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Children are exposed to more environmental contaminants than adults
because they eat, breathe, and drink more per unit of body weight. They
exhibit behaviors such as hand-to-mouth contact and crawling on floors where
chemicals accumulate in dust and on surfaces.
The following pages present research findings from the Children's Centers
on chemicals and pollutants in the environment children are commonly
exposed to through air, water, and food. This section includes the different
environments where children can be exposed, including outdoors, indoors at
home or at school, urban areas, and rural settings.
An average newborn
consumes 2.7 ounces of
milk or formula per pound
of body weight per day. For
an average male adult, this
is equivalent to drinking 35
12-ounce cans of a beverage
per day.1

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AIR POLLUTION	38
ARSENIC	42
CONSUMER PRODUCTS: BPA	44
CONSUMER PRODUCTS: PBDEs	46
CONSUMER PRODUCTS: PHTHALATES	48
LEAD	50
PESTICIDES	52
SECONDHAND TOBACCO SMOKE	56

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AIR POLLUTION
Lung function is measured by lung volume and air flow and is a marker
of respiratory health in childhood. As children grow and develop, their
lung function increases. Lung function in childhood can help predict how
healthy a person's heart and lungs will be in adulthood.4
Children who lived iessthan 500 meters (about one-third of a miie)
from a freeway had substantial deficits in lung function compared with
children who lived more than 1,500 meters (a little less than one mile)
from a freeway,5
• Abnormally low lung function was five times more common in children
living in communities with high levels of particulate matter (PM).4
Lung development was negatively affected in fourth graders exposed
to PM, nitrogen dioxide (NOJ, elemental carbon, and inorganic acid
vapor. Larger deficits were observed in children who spent more time
outdoors,6
• Children living near a major roadway were at increased risk for deficits
in lung function, even in areas with iow regional pollution. These
results suggest that children who live close to a freeway in areas with
high ambient pollution levels experience a combination of adverse
developmental effects because of both local and regional pollution.*
PUBLIC HEALTH ACTION
EPA considered over 75 publications
from the University of Southern
California, Columbia University,
and The Johns Hopkins University
Children's Centers in its Integrated
Science Assessments (ISAs) for air
pollutants including ozone, PM, and
NO/1® The ISAs serve as the scientific
foundation for establishing National
Ambient Air Quality Standards
(NAAQS). Under the Clean Air Act,
states must meet the NAAQS in
order to protect human health
and the environment.3 Children's
Centers findings cited in these ISAs
Include associations between air
pollution and low birth weight, lung
development, and asthma.
Through
mitigation and reduction
actions, levels of air
pollution dropped 70%
between 1970 and
201 MKi
Exposure to air pollution impacts people of all ages, but infants and children are
more vulnerable than adults to the many adverse effects. Children are exposed to
more air pollutants than adults because they have higher breathing rates, are more
physically active, and spend more time outdoors." Because their lungs and immune
systems are immature, children are particularly susceptible to the effects of air
pollution. Even a small deficit in lung growth during childhood can accumulate into
substantial deficits in lung function in adulthood.2 Air pollution can affect children's
health, especially their respiratory health. Air pollution is known to contribute to
upper and lower respiratory infections and asthma exacerbation, and some studies
have shown that exposure may also impact infant mortality, weight, and pediatric
cancer.1

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Since their inception, the Children's Centers have made important contributions to evidence linking prenatal
and early life exposures to air pollution and health effects in infants and children. The centers have improved
the understanding of links between air pollution, preterm birth, low birth weight, birth defects, lung development,
asthma, neurodevelopment, and autism spectrum disorder. This work informed policies that have improved
air quality in the U.S., supported clinical interventions that help keep children healthy, and increased the
accuracy of methods to measure air pollution^Children's Centers researchers have identified health benefits
of cleaner air: when air pollution is reduced, human health improves, especially for children and other sensitive
popuiations.
Traffic-related air pollution (TRAP) is a potential risk factor for several pregnancy outcomes, including preterm birth and
structural birth defects. The UC Berkeley/Stanford University Children's Center has conducted some of the iargest studies	^
on the combined effects of air pollution and neighborhood deprivation. This research has substantially extended the	f
knowledge base concerning birth defects that may be associated with gestational exposures to l RAP.™	g-
•	Studies showed that the combination of TRAP and socioeconomic status influenced the risk of neural tube defects, a	£
3
severe group of birth defects. The combined influence of these factors was not previously demonstrated.1^®	°
•	Exposure to selected air pollutants appears to substantially increase the risk of early preterm birth (less than 30 weeks).?5
PUBLIC HEALTH ACTION
Studies supported by the University of Southern California Children's Center have provided the scientific foundation for
adoption of new policies at the locai and state ievel, including for an ordinance stating that new schools should not be located
near freeways with high traffic volumes, as required by California law." A summary of the University of Southern California
studies on health effects in proximity to freeway traffic was presented to the Los Angeles City Council before adopting an
ordinance that requires multi-family housing units built in the city to have special filters if they are constructed within 1,000 feet
of a freeway. The filters capture pollutants and help reduce at-home exposure to TRAP.®
39

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Reducing air pollution exposure could lead to substantial public health benefits.?For example, levels of air
pollution decreased in Los Angeles from 1992 to 2011. Studies from this 20-year period show health benefits
to children as a result of the improved air quality.18,19 When levels of PM and N02 were reduced, lung function
improved and bronchitis symptoms decreased in children with and without asthma. Reductions in bronchitis
symptoms were more pronounced in children with asthma.
Placing air cleaners containing high-efficiency particulate air (HEPA) filters in children's bedrooms resulted in a sustained
reduction in PM levels. During a randomized, controlled trial, center researchers found that this simple, feasible
intervention achieved a substantial reduction in indoor PM levelsS Portable HEPA air cleaners were also shown to
significantly reduce PM exposure for children living with someone who smokes. Researchers estimate that these
reductions could mean that a child is free of asthma symptoms for 33 more days per year.®

Prenatal exposure to PAH

was associated with adverse

effects on child cognitive
>
¦M
and behavioral development
'55
i-
>
assessed through age 9 years,
'E
alone or in combination
rc
15
with materia! hardship due
£
3
to poverty;3® The researchers
O
u
calculated significant economic

benefits from a modest

reduction in air PAH levels in

New York City?
PUBLIC HEALTH ACTION
Particles from diesel emissions can contribute to asthma onset and asthma
exacerbation in children. Columbia University's Children's Center research
was cited by community partner WE ACT for Environmental Justice to
support an evidence-based campaign that helped New York Metropolitan
Transportation Authority (MTA) convert to compressed natural gas buses,
hybrid buses, and the use of ultra-low suifur diesei,1'® Center findings on the
harmful impact of diesel soot helped pass New York City Local Law 77, which
mandated that all large vehicles, including the MTA bus fleet, convert from
dirty to ultra-low sulfur diesel, resulting in vehicles that emit 95 percent less
tail pipe pollution.'0
40

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Using advanced methodologies for
exposure assessment, researchers showed
associations between PAH exposure and
childhood wheeze, immunological function,
and preterm birth.13'2MrI This research
pushed the field forward by characterizing
exposures to criteria pollutants, while
also incorporating important non-criteria
pollutants such as PAHs, elemental carbon,
and endotoxin.
Distribution of PAHs in FreSfio, California, based on extensive sampling. Darker areas
reflect higher levels of PAHsP
PUBLIC HEALTH ACTION
Heating oil combustion, which is common in New York City for residential heating, releases ambient metals, which can cause
respiratory symptoms in young children.33
• Columbia Center investigators and community partner WE ACT for Environmental Justice helped to provide education and
testimony to inform the debate on the phasing out of dirty heating oils Number 4 (No. 4) and Number 6 (No. 6).
¦ In April 2011, the New York Department of Environmental Protection adopted a regulation that required aii buildings to cease
burning No. 4 and No. 6 heating oils by 2015 and 2030 respectively.
41

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BACKGROUND
Dietary exposure to arsenic is a potential health risk that begins early in life.31
Arsenic is found in water, soil, and air as a result of naturally-occurring processes
and historic and current use in arsenic-based pesticides,35 While most arsenic-based
pesticides were banned in the U.S. in the 1980s, residues of this chemical element
are still found in soil.1®As a result, food and drinking water can contain levels of
arsenic that exceed federal health risk targets.® Rice-based products can be high in
arsenic and are often introduced into a child's diet during infancy.® Because young
children have iess varied diets, it is estimated that they may have two to three times
higher arsenic exposure from food than adults.3? Children are also exposed to more
arsenic than adults because they play in the dirt and put their hands in their mouths.3®
Untii recently, very little was known about the health impacts of arsenic on children.
Research conducted in the past several years has advanced knowledge on dietary
sources of arsenic in children and potentially related health effects. Findings included
in this report are regarding inorganic arsenic compounds, which are highly toxic.38
More than 15 million
U.S. households
depend on private
wells for drinking
water, particularly in
rural areas, and may
be exposed to high
levels of arsenic.33
Dietary exposure to arsenic is a potential health risk that begins early in life.34'
•	An example of dietary arsenic exposure to infants was organic toddler formula, which contained brown rice syrup. This
formula had total arsenic concentrations up to six times the EPA safe drinking water limit.*
•	Consuming water and food with low levels of arsenic while pregnant may affect fetal growth. Maternal urinary arsenic
concentration was associated with a reduction in infant head circumference. Evidence suggests that fetal growth is an
important predictor of adult health.*' This study was one of the first to report an association between low-level arsenic
exposure during pregnancy and birth outcomes.*1*'
•	In utero exposure to arsenic may alter the fetal immune system and lead to immune dysregulation. Infants prenataliy
exposed to arsenic were at higher risk for respiratory infection and wheezing.mm
•	Prenatal exposure to low levels of arsenic had effects on the infant's epigenome. The epigenome is made up of
chemical compounds that can tell human genes what to do, and may be a key mechanism of arsenic's long-term health
effects:*1
•	Research has also focused on mechanisms of arsenic toxicity in infants and adults and identified the arsenic
transporter AQP9 as a potential fetal biomarker for arsenic exposure.4®
42

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Given the overall scarcity of studies on the effects of early-life exposure to arsenic, the Dartmouth College Children's Centers
research on this topic is essential in protecting children's health. Findings from this center have provided evidence for
associations between arsenic, fetal growth, and immune function,^^Hn early draft of the EPA Integrated Risk
Information System (IRIS) assessment of arsenic includes research from the Dartmouth College Children's Center on early-life
exposure. Once final, the IRIS assessment will be used by other federal, state, and local agencies to assess human health risks
from arsenic exposure «This center is also engaging with the community to create educational materials for families to help
reduce their arsenic exposure. This research demonstrates the need to continue exploring the effects of arsenic exposure,
especially at low levels, on children's health.
PUBLIC HEALTH ACTION
In Aprii 2016, the U.S. Food and Drug Administration (FDA) took its
first regulatory action to limit the amount of arsenic in rice products.
The proposed limit of 100 parts per billion in infant rice cereal was
based on FDA's assessment of the health risks that arsenic in rice and
rice products pose. FDA cited several Dartmouth College Children's
Center studies examining the effects of arsenic exposure, mechanisms
of arsenic toxicity, and the relationship between dietary and drinking
water exposure sources;*
Research from the Dartmouth College Children's Center informed
federal legislation to limit arsenic in rice. As of November 2016,
the proposed R.I.C.E (Reducing food-based Inorganic Compounds
Exposure) Act has been referred to the House Energy and Commerce
Subcommittee of the Health and House Agriculture Committee,:4'
IMPACT ON COMMUNITIES
The Dartmouth College Children's Center
is collaborating with a network of primary
care physicians and pediatricians to inform
families about the potential health effects
associated with arsenic exposure and to
encourage private well testing. They provide
potential strategies for families to reduce
arsenic exposure from rice for their infants
and children, including diversifying the
diet and adopting strategies to minimize
exposure,5®The center has developed an
interactive web-based tool that educates
parents and the public about sources of
arsenic and how they can reduce exposure.51
43

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More than
6 billion
pounds of bpa
are produced
worldwide
every
year.58

CONSUMER PRODUCTS: BPA
BACKGROUND
Bisphenol A (BPA) is used in a variety of consumer products, including water bottles,
baby bottles, toys, food can linings, medical devices, and ATM receipts.®'5® People are
exposed to BPA mainly through eating food or drinking water stored in or processed
with BPA-containing plastics. It may also be absorbed through skin or inhaled.5* There
are questions about BPA's potential impact on children's health, since animal studies
have shown it is a reproductive and developmental toxicant.54*®''
While some studies indicate that BPA levels in humans and the environment are below
levels of concern for adverse effects, other recent studies describe subtle effects in
animals at very low levels, leading to concerns for potential effects on children's health
even at low doses.57
Exposures to BPA during prenatal and early childhood development were associated with multiple measures of body
composition, suggesting that BPA may contribute to childhood obesity.
Children exposed to high levels of BPA had lower body mass index (BMI) at age 2 years, but BM! increased more rapidly
from ages 2 to 5 years.®®
Children with higher prenatal exposures to BPA had a higher fat mass index, percent body fat, and waist circumference
at age 7 years.6'?
Children exposed to higher levels of BPA showed increased amount of body fat at age 9 years;61 Higher prenatal
exposures showed differences in adiponectin and ieptin in 9-year-old children, suggesting that mechanisms of BPA
toxicity may interact with metabolic pathways."5
Children with higher exposure to BPA early in life had increased skinfold thickness, as well as higher triglycerides, Ieptin,
and glucose at age 8 to 14years®3*®

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Several Children's Centers have conducted research on exposures and related health effects of chemicals commonly found
in consumer products, such as BRA, PBDEs, and phthalates, which are explained in more detail in the next sections. There
is growing evidence linking these endocrine-disrupting chemicals to neurobehavioral problems, obesity, and
reproductive effects.1®* Important findings from the Children's Centers have informed legislative and market actions both
nationally and internationally to help reduce exposures and protect children's health. The Children's Centers engage with the
community to reduce exposures from consumer products. For example, through a youth participatory research project, the UC
Berkeley (CERCH) Children's Center empowered children and teenagers to examine exposures from cosmetics and personal
care products.
PUBLIC HEALTH ACTION
The Children's Safe Product Act fCSPA) requires manufacturers to report the concentration of 66 chemicals of high concern in
any children's products sold or manufactured in Washington state.7® The University of Washington Children's Center worked
with the Washington State Department of Ecology to prioritize data collected under CSPA. This collaboration resulted in a
framework that incorporated both exposure and toxicity factors to identity critical products and chemicals for future monitoring
and action,38
Prenatal BPA exposure in mice had negative effects on the development of the reproductive system, even multiple
generations after exposure. Investigators studied mice exposed to BPA while pregnant and the resulting reproductive
effects on the first (equivalent to children), second (equivalent to grandchildren), and third (equivalent to great-
grandchildren) generations.
£L
rt
•	The female children and grandchildren of mice exposed to BPA while pregnant showed a reduced ability to maintain
pregnancies.8®
O
5T
•	The female great-grandchildren of mice exposed to BPA while pregnant had more difficulty becoming pregnant.54
•	The female great-grandchildren of mice exposed to BPA while pregnant reached puberty at a later age,8'
45

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ll
M
A northern California
study found
100% of
women they
tested had been
exposed to PBDEs.73
BACKGROUND
Polybrominated diphenyl ethers (PBDEs) are a group of chemicals used as flame
retardants in textiles, furniture foam, carpet padding, building materials, upholstery
in cars and airplanes, and plastic housings for electronics,72 Recent evidence
suggests PBDE exposure may interfere with the body's natural hormones and disrupt
mental and physical development?2 As furniture and other products age, flame
retardants can be released into the surrounding environment where they remain
for years. Dust containing PBDE particles is one of the main routes of exposure to
PBDEs, especially for young children who put their hands or toys in their mouths.
PBDEs have been linked to unhealthy changes in growth and development, and can negatively impact
>. maternal and child health.72 Higher PBDE exposure during pregnancy was associated with babies having
! u lower birthweight741® Additionally, PBDE exposure was associated with lower levels of maternal thyroid-
« o stimulating hormone during pregnancy, which couid have implications for maternal health and fetai
developments Women exposed to higher levels of PBDEs also took a longer time to become pregnant,
suggesting that PBDEs may affect fertility.^'7'5
Exposures to PBDEs during prenatal and early childhood, at a time when the brain is rapidly developing, are particularly harmful.
When compared to children with lower exposure, children with high prenatal exposure to PBDEs displayed:
f * Lower scores on mental and physical development tests at age 1 to 4yearsP
|Hy • Twice the number of attention problems at ages 3, 4, and 7 years.83*
• More hyperactivity problems and a decrease of 4.5 IQ points at age 5 years,68
I • Poorer behavioral regulation and executive functioning at ages 5 and 8 years.®
46

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See page 45
PUBLIC HEALTH ACTION
Californians have high exposure to flame
retardants because these chemicals were
used to meet the state's previous furniture
flammability standard,72 In 2012, California
implemented a new flammability
standard.78 Furniture and baby product
manufacturers can now meet the new
standard without toxic flame retardant
chemicals* This action was based In part
on findings from the UC Berkeley (CERCH)
Children's Center,® Although this action
effectively eliminated the need for flame
retardants in household furnishings,
it is not an overall ban.74*
Both prenatal and childhood PBDt exposures were associated with poorer attention, fine motor	c
s O
coordination, and cognition of school-age children.®^®' This is one of the largest studies to evaluate cognitive £ "
declines in school-aged children exposed to PBDEs. This research contributes to a growing body of evidence i m
w fD
suggesting that PBDts have adverse impacts on child neurobehavioral development	^
47

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CONSUMER PRODUCTS: PHTHALATES
BACKGROUND
Phthalates are commonly found in personal care products such as
shampoo, perfume, makeup, and lotion. They are also found in plastic
products such as toys, shower curtains, medical tubing, car upholstery,
food packaging, and many others#2 Such widespread use means that
people are exposed to phthalates every day®8 Possible adverse health
outcomes from phthalate exposures include disruption of the body's
natural hormones and impaired brain development. Exposures are
particularly harmful during pregnancy, when they can disrupt fetal
developments^®5 Because many personal care products are designed
to be absorbed into the skin and have long lasting fragrances, chemicals
can easily enter our bodies#6 While adults are mainly exposed through
using personal care products, eating contaminated food, and inhaling
indoor air, infants and toddlers can also be exposed by ingesting indoor
dust that is contaminated with phthalates.8*
17 Products
The average number of
personal care products used
by a teenage girl per day* In
comparison, an adult woman
uses 12 products, and an adult
man uses 6 products.88,89
Tiiili
Prenatal exposure to phthalates negatively impacts pregnant women and birth outcomes.
•	Exposure to phthalates and BPA is associated with biomarkers of angiogenesis, or formation of new blood vessels,
during pregnancy. This may indicate disrupted placental development and function.®?
•	Exposure to phthalates during pregnancy are associated with increased oxidative stress biomarkers, which can lead to
preeclampsia, intrauterine growth restriction, and other pregnancy outcomes;91'
Prenatal exposure to phthalates negatively impacts reproductive development in mice, such as:
•	Decreased sperm motility and premature reproductive aging in male mice®*
•	Disruption of several aspects of female reproduction, including ovarian cysts and a disrupted estrous cycle (equivalent
to the human menstrual cycle).35
•	Direct damage to the ovaries, increased uterine weight, decreased anogenital distance, induced cystic ovaries,
disrupted estrous cyclicity, reduced fertility-reiated indices, and some breeding complications at age 3, 6, and months
in female mice.94*
48

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IMPACT ON COMMUNITIES
As part of the UC Berkeley (CERCH) Children's Center, the Health and Environmental Research in Make-up Of Salinas
Adolescents (HERMOSA) Study was led in partnership with youth in Salinas Valley, California, to examine how girls are
exposed to hormone disrupters, like phthalates in personal care products.®5'The study was featured in local and national
news broadcasts including ABC's Good Morning America* and National Public Radio (NPR).® Results showed that chemicals
in personal care products used by teenage girls are absorbed into their bodies. The study also found that exposures can
be reduced when users switch to products that contain fewer chemicals. Through this study, researchers empowered local
youth by engaging them in many aspects of research, including design, data collection, analysis, and communicating findings
with the community, policy makers, and media. The findings are also important because there is little information about how
exposure to hormone disrupting chemicals during adolescence may impact long term health.
"Personally, since the [HERMOSA] study, I've tried to use
more natural products. It's hard, especially as a college
student who doesn't have a lot of money... I've decided
to splurge more on products with fewer chemicals
because of the effect in the future."
- Maritza Cardenas, teen researcher and HERMOSA study co-author.4®
Phthalates found in household dust may have negative effects on children's brain development.
¦ Higher levels of phthalates in household dust were associated with poorer adaptive functioning and developmental
delays in children 2 to 5 years old:*
• When researchers restricted their analysis to maie children oniy, they found that phthalates were associated with
hyperactivity, impulsivity, and attention problems.®9
49

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As a child's blood lead
level increases from 1 to
10 pg/dl, a child may
lose anywhere
from 3.9 to 7.4 IQ
points.1® Chronic
low level exposure to
lead may have an even
greater effect on IQ than
a single instance of high
level lead exposure.
BACKGROUND
Levels of lead in children's blood have declined tremendously since the 1970s.rd6'lW
While substantial progress has been made to reduce children's exposure to lead,
approximately half a million U.S. children 1 to 5 years old still have blood lead levels
above 5 micrograms per deciliter (pjg/dL) — the reference level that the Centers
for Disease Control and Prevention (CDC) recommends public health action.'® The
number of children who continue to be exposed to lead is alarming, since research
demonstrates that even low levels of lead exposure can affect IQ, attention, academic
achievement, and cause iong-term mental and behavioral probiems.IQHW The
Children's Centers have been working to better understand the health effects of lead
at even the lowest levels of exposure. Research shows that there is no safe level of lead
exposure for children, and the most important step that parents, doctors, and others
can take is to prevent lead exposure before it occursJ™3
Lead has significant and long-term impacts on the nervous
system. Studies using advanced neuroradiological methods
from the Cincinnati Children's Center were the first to
document persistent lead-related damage to areas of the
brain responsible for cognitive and language functions.
•	Childhood lead exposure impacts brain reorganization and
language function. Damage to the primary language areas
in the brain's left hemisphere resulted in compensation by
the brain's right hemisphere:1®-
•	Higher rates of total criminal arrests and arrests for violent offenses during young adulthood have been linked to
prenatal and early childhood lead exposure. The likelihood of being arrested for a violent crime as a young adult
increased by almost 50 percent for every 5 pjg/dL increase in blood lead levels at age 6 years.1® This study was the first
to document the relationship between childhood lead exposure and young adult criminal behavior.
•	Reductions in adult gray matter volume in regions of the brain responsible for executive functions, mood regulation,
and decision-making were associated with childhood lead exposure. These findings were more pronounced in
males.™
Regions of the brampi red.and yellow) show declines tnbrain
gray matter volume associated with ehil.dhood blood lead
concentrations.®
50

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Children's Centers research is vital to demonstrating and halting the detrimental health effects of lead exposure
to children at low levels. EPA cited nearly 40 Children's Centers publications in its Integrated Science Assessment (ISA) of
Lead in 2013.111 The ISA serves as the scientific foundation for establishing National Ambient Air Quality Standards (NAAQS)
for lead. Under the Clean Air Act, states must meet the NAAQS in order to protect human health and the environment,3 EPA
cited several Children's Center studies as evidence for a causal relationship between lead and the following effects observed
in children: impaired cognitive function, poor fine motor skills, increased risk for criminal behavior, and altered brain structure
and function. Simple steps to reduce exposure to lead are essential to protect children's health. The University of Michigan
Children's Center collaborated with the Flint Water Task Force to create a training for community members and health workers
who provide nutrition education to the Flint community. The training provides nutritional information and guidance on nutrients
and culturally relevant foods to reduce lead absorption in young children. The centers have created knowledge essential for
effective action and made use of existing knowledge to reduce lead exposure and protect children's health*
Childhood lead exposure has been linked to a number of adverse cognitive outcomes, including reduced performance on
standardized IQ tests, neurobehavioral deficits, poorer test scores, and classroom attention deficit and behavioral problems.1
End-of-grade test scores on elementary school achievement tests were lower for children who had higher blood lead
levels. A strong relationship was seen between increased early childhood lead exposure and decreased performance on
elementary school achievement tests.1®7
Intelligence test scores were lower for children who had higher blood lead levels. Findings showed a 3.9 IQ point
decrement associated with an increase in blood lead from 2.4 to 10 pg/dL,1®
Symptoms related to Attention Deficit Hyperactivity Disorder (ADHD), specifically hyperactivity and restless-impulsivity
behaviors, were positively associated with low blood lead levels (equal to or less than 5 pg/dL).w
51

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BACKGROUND
Studies have demonstrated widespread pesticide exposures for the U.S. population,
including pregnant women and children.11^120 Exposure to pesticides may be linked to
adverse developmental, cognitive, and behavioral outcomes. Children are especially
susceptible to pesticide exposure because they have higher rates of metabolism, less-
mature immune systems, unique diets, and distinct patterns of activity and behavior
when compared with adults.® For example, children spend more time outdoors
on grass and fields where pesticides might be. Children also spend more time on
the ground and tend to have more frequent hand-to-mouth contact than adults*
Furthermore, children's diets are usually less varied than adults, which could increase
their intake of foods containing pesticide residues.® Of particular concern are
organophosphate (OP) pesticides because of their toxicity and widespread use.,aft
More than one
billion pounds of
pesticides are used
each year in the U.S.,
with more than
700 million
pounds used
annually in
agriculture.1^

Both the UC Berkeley (CERCH) and the University of Washington Children's Centers have found that farmworkers and their
children are exposed to higher levels of pesticides than the general population and therefore, may experience more adverse
health effects.115-133
•	Children prenatally exposed to higher levels of OP pesticides exhibited poorer cognitive functioning compared
to children exposed to lower levels.1®"13"
•	Women experienced shorter duration pregnancies^
•	infants showed more abnormal reflexes soon after birthj19Children scored lower on tests for psychomotor
S1 „ development at ages 6 and 12 months, and on tests for mental development at ages 12 and 24 months,?*
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"The center's research
about the exposure of
pregnant women and
newborns to pesticides
motivated Local Law
37 and put New York at
the forefront of safer
pest control methods
in the United States."
- Michael Bloomberg,
former New York City
Mayor;13®
The Children's Centers have documented that pre- and postnatal exposure to pesticides is linked to various adverse health
effects such as autism spectrum disorder, poorer cognitive function, lower IQ, attention problems, low birth weight, and
ieukemia in children. Children's Centers researchers have examined how age, genetics, and environmental factors
influence children's susceptibility to the harmful effects of pesticides, which can affect growth, development,
and learning. Center research has led to public health policies designed to better protect children and infants from harmful
pesticide exposures. Children's Centers research on pesticides has been translated to farmworkers and their families to reduce
exposures and to protect health. While great progress in reducing children's exposure to pesticides has been made, a greater
understanding of the exposure pathways of pesticides, the long-term heaith effects of pesticides, and methods to reduce
pesticide exposure remains essential.
Prenatal exposure to chlorpyrifos can interfere with children's brain development (see page 29). Chlorpyrifos was
commonly used as an insecticide in residential settings before it was banned for domestic use by EPA in 2001 JmThis
action had a positive effect on public health and quickly resulted in reduced levels of chlorpyrifos in the umbilical cord
blood of babies, as demonstrated by evidence from the Columbia University Children's Center.1'®'
At the heart of the UC Berkeley (CERCH) Children's Center is the center for the Health
Assessment of Mothers and Children of Salinas (CHAMACOS) study. CHAMACOS is the longest
running longitudinal birth cohort study of pesticides and other environmental exposures
among children in a farmworker community. It is also one of the only cohorts focused on
low-income, Latino children in a farmworker population. Since 1999, CHAMACOS has enrolled
pregnant women living in Salinas Valley, California, one of the most productive agricultural
regions in the nation. More than 600 children continue to participate in the study and will be
followed until adulthood.
Newborns have very low levels of the critical enzyme PON1, which can detoxify OP pesticides. Levels of PON1 remain low c
v n
through age 7, indicating that childhood is a time of increased vulnerability to pesticide exposure. Some adults may also £ %
have lower PON1 enzyme activities and levels, demonstrating differential susceptibility to exposures in adults as well. This x ®
W fD
was the first study to examine PON1 variability by age and genetics in children:**®	*=
53
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PUBLIC HEALTH ACTION
The EPA Worker Protection Standard (WPS) is designed to reduce pesticide exposure and protect farmworker heaith. In
November 2015, EPA updated and strengthened the WPS for pesticides to protect farmworkers and their families. EPA
considered research from the UC Berkeley (CERCH) and University of Washington Children's Centers to support the new
standard,,3Vl;*y®# As part of the strengthened WPS, new rules are in place to prohibit children under 18 from handling
pesticides. Additional education requirements now address take-home pathway exposures to farmworker families, and
pesticide safety training is required every year. The UC Berkeiey (CERCH) Children's Center is actively developing opportunities
to conduct WPS trainings in agricultural communities throughout California.
When farmworkers go home after work, they may contaminate their cars and homes with pesticide residues from their skin and
clothes. Family members may then be exposed to these residues. This route of exposure is called the take-home pathway.
•	Studies show that the take-home pathway contributes to pesticide contamination in homes of farmworkers
where young children are present.*4®
•	Concentrations of agricultural pesticides were higher in the homes and vehicles of farmworkers compared to
those of non-farmworkers. This suggests that the vehicle used for travel to and from work can be a source of
exposure for family members..?®*w^118
•	The use of protective clothing, gloves, and hand-washing are known to reduce pesticide exposure to workers.
| x However, these protective measures do not address the potential for the take-home pathway. A community-
| £ based intervention designed to reduce children's exposure to pesticides through the take-home pathway found
^ " that farmworkers can reduce pesticide exposure to their families by wearing gloves and removing work clothes
before returning home.1*4®
PUBLIC HEALTH ACTION
Informed by scientific findings from the UC Berkeley (CERCH) Children's Center, the California Department of Pesticide
Regulation is developing new guidelines limiting pesticide applications near schools and day care centers. The new policy
would require additional communications between pesticide applicators, school administrators, and parents. Researchers also
presented testimony on this subject to the California Senate Environmental Quality Committee.1®
54
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IMPACT ON COMMUNITIES
The University of Washington Children's Center developed the "For Healthy Kids!" program to reduce the take-home pathway
of pesticide exposure in farmworker households. In total, center staff conducted over 1,500 separate activities that reached
close to 15,000 people. The program targeted behavioral interventions to specific communities and disseminated information
on reducing exposures at health fairs, schools, and home health parties. They distributed "Keep Me Pesticide-free" bibs to
newborns, soap kits for washing clothes separately, and many more materials to community members. These activities resulted
in modest changes in certain behaviors among farmworkers^Researchers conducted a results analysis of study participants
and found that the community supported this style of research messaging.1®
PUBLIC HEALTH ACTION
Integrated Pest Management (IPM) is an environmentally friendly approach to controlling pests. IPM uses strategies such as
identification, monitoring, and prevention to minimize pesticide use. Findings show that IPM practices are successful in reducing
pest counts in apartments while also reducing exposure to pesticides.1^5®5in an effort to reduce the impact of pesticide
exposure, New York City lawmakers have passed legislation and revised health codes that encourage the use of IPM. Many of
these laws and codes cite the work of the Columbia University Children's Center.
•	Neighborhood Notification Law (Intro 328A), 2007. This law created requirements about providing sufficient notice to
neighbors about certain pesticide applications.1'®
•	NYC Pesticide Reduction Law (Intro 329A, Local Law 37), 2007. This law established requirements related to the use of
pesticides and promoted IPM practices®8
•	NYC Health Code (Article 151), 2008. The revised code includes a section calling for pest management measures other than
pesticide use and specifically stated, "Pesticide use shouid not be the first and only line of defense against pests.*1®5
55
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BACKGROUND
Children have no control over their indoor environment, including where and
when adults smoke. Secondhand tobacco smoke (STS) is a complex mixture
containing more than 7,000 chemicals.1® The numerous toxic and carcinogenic
compounds found in STS can result in negative health effects, including
preterm birth, impaired fetal growth, respiratory illness, and neurological
problems, all of which can persist into adulthood.1®'1®6 Children's Centers
research has clarified the relationship between STS and childhood leukemia,
asthma, and neurodevelopment.
40% of nonsmoking
children 4 to 11 years old had
measurable levels of cotinine
in their bodies in 2011-2012.
Cotinine is created when the
body breaks down
nicotine found in
tobacco smoke.1®
V
STS has been proven to cause cancer in adults.'® Until recently, little was known about STS exposure at critical periods
of development and childhood cancer. This center was one of the first to study the effects of cigarette smoking in both
», fathers and mothers. Research found that paternal smoking before conception and STS exposure during early childhood
| ^ can result in acute lymphoblastic leukemia and acute myeloid leukemia.1® Prenatal paternal smoking and STS were
¦ 8 associated with a chromosome abnormality (translocation) caused by a rearrangement of parts between chromosomes
12 and 21. This translocation nearly always occurs in the fetus before birth, often hiding for years before leukemia
develops.1®6 Identifying chromosome abnormalities allows researchers to better identify types of leukemia associated
with specific exposures.
Poor recaii of smoking history may explain why most epidemiological studies have not found an association between
maternal smoking during pregnancy and the risk of childhood leukemia. Researchers used methylation biomarkers to
better characterize maternal smoking. They found that exposure to STS, particularly from mothers, may alter the DNA of
leukemia cells.
The amount of smoke exposure in the environment of the child is positively associated with the numbers of genetic
deletions in leukemia cells. This suggests that smoke exposure before and after birth is continuously capable of inducing
genetic damage, and removing smoke from a child's environment at any time can potentially stop further damage from
occurring.®
56
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"Approximately
2 percent of
leukemia cases in
California could be
avoided if children
were not exposed
to tobacco smoking
at any given point."
- Catherine Metayer, M.D.,
Ph.D., Director, UC Berkeley
(CIRCLE) Children's Center.

Multiple Children's Centers have contributed to research on STS, focusing on the relationship to asthma,
childhood leukemia, and neurodevelopment. Through their research, the Children's Centers show that STS can affect
genes related to asthmatic and aiiergic responses in children. The centers have provided evidence that STS can exacerbate
allergic effects and that exposure to STS can vary by socioeconomic status. The Children's Centers have disseminated their
research findings to the community. With each step forward, Children's Centers research continues to identify ways to lessen or
prevent effects of STS exposure.
Maternal smoking during pregnancy can affect the respiratory health of her child. Maternal and grandmaternal
smoking during pregnancy increased risk of childhood asthma.11® Additionally, the risk of asthma onset in adolescents
who smoked cigarettes regularly was more pronounced in those whose mothers smoked during pregnancy.1® Risk of
respiratory-related school absences also increased among children exposed to STS, regardless of whether or not they
had asthma.®
The complex mixture of chemicals in tobacco smoke has the potential to affect children's neurodevelopment by a variety
of different mechanisms. Exposure to the entire mixture of compounds in STS had long-lasting negative effects on
neurodevelopment that were much greater in magnitude than nicotine exposure alone.18®® It is important to minimize
or eliminate prenatal and childhood STS exposure since efforts to minimize the neurodevelopmental effects of STS
have been thus far unsuccessful. These in vitro studies included nicotinic receptor blockades, antioxidants, and methyl
donors.1®8
IMPACT ON COMMUNITIES
A major health issue in Baltimore is the impact of STS and other air pollutants. Investigators from The Johns Hopkins University
Children's Center met with the Baltimore City Health Department to learn about the effectiveness of IHEPA air cleaners and
educational interventions for STS reduction. The health department then developed a pilot intervention study using HEPA air
cleaners, which has been successful in improving air quality in homes of pregnant mothers and babies who live with someone
who smokes.
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The Children's Centers have collectively pushed the boundaries of clinical,
field, and laboratory-based research through novel and interdisciplinary
approaches that include both animal and human studies designed to reduce
the burden of disease in children.
Following children from preconception through childhood has enabled a
greater understanding of the effects of environmental exposures on childhood
diseases, and allowed for the collection of samples over time. These archives
of biological and environmental samples serve as a tremendous resource for
future studies and provide critical information on the prenatal and childhood
determinants of adult disease.
The centers have translated scientific findings to provide practical information
and actionable solutions leading to healthier children and a healthier society.
The following pages give examples of the unique features that have facilitated
the Children's Centers' work and advancements in the field.
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COMMUNITY OUTREACH AND RESEARCH TRANSLATION	60
EXPOSURE ASSESSMENT	64
INTERDISCIPLINARY APPROACHES	66
NEW METHODS AND TECHNOLOGIES	68
POPULATION-BASED STUDIES	70
RODENT MODELS	72
SAMPLE REPOSITORY	74
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BACKGROUND
Many times scientific concepts and research results are not easily understood by
the general public. Empowered by program requirements', the Children's Centers
have successfully communicated and applied research findings to protect children.
The centers have provided the public, community organizations, healthcare
professionals, decision makers, and others with practical information about the
science and actionable solutions that link the environment to children's health.
These achievements are largely due to the work of their Community Outreach
and Translation Cores as well as input and direction from community advisory
boards. The center structure and effective partnerships drive research design,
lead to practical interventions, and create culturally-appropriate communications
and educational resource materials that serve the community. Through their
efforts, the centers have mobilized community members to participate in planning,
implementing, and evaluating the effectiveness of interventions and public health
strategies for healthier children, families, and future generations.
The Children's Centers have developed and disseminated outreach
materials that are critical for educating communities about children's
environmental health topics. For example, the UC San Francisco Children's
Center developed and disseminated a patient-centered series of culturally-
appropriate brochures to counsel women and men who are planning a
family, as well as pregnant women, on how to prevent harmful exposure
to environmental contaminants;?The brochures are now being developed
into a mobile app. The materials are highly engaging and interactive,
such as the web tool developed by the Dartmouth College Children's
Center to help families decrease their risk from exposure to arsenic in
food and water.3 Another example is the series of infographics created by
the USC Children's Center to communicate risks of air pollution across
the life course; these infographics received an award from the National
Academy of Science Engineering and Medicine.4 Many of the Children's
Centers, including the center at UC Davis, designed brochures in multiple
languages to be distributed in places like community clinics, support
groups for Latina mothers, and the Mexican Consulate in Sacramento.
s- <0
E ¦£ '1
111
C w tc
More than 1,500
separate outreach
activities that
informed 15,000
people about ways
to reduce their
environmental
exposures.
- University of Washington
Children's Center.

The UC San Francisco

Children's Center

developed the

Environmental Health

Inquiry Curriculum, an

eight-hour in-depth
o
u
course for all first year
u
c
medical students. This
0J
i-
LL.
medical school training
s
to
is the first of its kind, and
(J
3
covers scientific concepts,

critical literature appraisal,

and application in clinical

settings. The training is

part of UC San Francisco's

medical school curriculum

for 2017.
60
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w-


¦S*yi
¦f tp
T&iHm
"Starting today,
everything will change.
I learned techniques
on how to protect
my children from
pesticides exposure,
my family will benefit
in addition to people
of my community."
- CHAMACOS study trainee.
The partnership between the UC Berkeley (CERCH) Children's
Center and the farmworker community in Salinas Valley has
been the cornerstone of the center's success and impact.
This center has pioneered more effective methods to provide
individual results to study participants. They have worked closely
with community partners for aimost two decades to provide
information to farmworker families on preventing pesticide and
other environmental exposures. The center has given more than
1,000 presentations reaching over 25,000 people and developed
brochures to promote healthy homes for farmworkers. They are
working with the California Migrant Education Program to expand
trainings statewide.
The UC Berkeley (CERCH) Children's Center also collaborated
with Clinica de Salud del Valle Salinas to develop an innovative,
computer-based prenatal environmental health kiosk: a cuituraliy-
appropriate software that teaches pregnant women about
environmental health concerns to be aware of during pregnancy.
Prenatal environmental health brochures on asthma, allergies,
lead, pesticides, and carbon monoxide accompanied the kiosk.
The UC San Francisco Children's Center effectively collaborated with women's health professionals to engage the clinical
community in efforts to prevent harmful environmental exposure through clinical, educational, and policy efforts. The
leading women's health professional societies in the U.S. and globally called for action to prevent harmful environmental
exposures.5,6 Eleven Children's Center's studies, including publications from the UC San Francisco Children's Center,
were cited by the American College of Obstetrics and Gynecology and the American Society of Reproductive Medicine as
evidence that environmental chemicals can adversely impact reproduction. The International Federation of Obstetrics ^EjB
and Gynecology (FIGO) also cited Children's Centers studies in their 2015 opinion paper. The FIGO opinion was amplified Ifjfl
by a summit that brought together 50 leaders of reproductive health professional societies from 22 countries to develop
an action plan addressing the global threat of environmental chemicals to reproductive health. The plan served as a
starting point for the newly formed FIGO Reproductive Developmental Environmental Health Work Group that is carrying
the action plan forward.
61
CHAMACOS participant, age 12,sh&wing the t-shift she was
given at birth wiHft sta was enrolled id She study.
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When people get sick or develop a disability, they often ask their health care providers, "How or why did this happen?" In
some cases, the answer is obvious. In others, it's more complicated. A Story of Health is a multimedia e-book told through
the lives of fictional characters and their families - Brett, a young boy with asthma; Amelia, a teenager with developmental
disabilities; and Stephen, a toddler recently diagnosed with leukemia. Each fictional case features the latest scientific
research about disease origin and helpful facts about disease prevention. The e-book can help families explore the risk
factors for disease as well as how to prevent disease and promote health, ft was developed by the UC Berkeley (CIRCLE)
Children's Center, the Western States Pediatric Environmental Health
Specialty Unit (PEHSU), Agency for Toxic Substances and Disease
Registry (ATSDR), the Collaborative on Health and the Environment,
the Office of Environmental Health Hazard Assessment, California
Environmental Protection Agency, and the Science and Environmental
Health Network. A Story of Health is available online.7 More than 7,500
health professionals have registered for continuing education credits
available from the CDC for completing chapters.

U
U
3
"A Story of Health is
compelling, educational and
engaging, and will absolutely
make a difference."
- Dr. Brian Linde, Pediatric Hospitalist,
Kaiser Permanente.
With guidance from their community advisory board, the Denver Children's Center developed outreach materials for
school-aged children and public health professionals. They designed 20 publicly-avaiiable lesson pians in environmental
education related to air quality with supporting resources that comply with public school education science curriculum
requirements.8 As of August 2017, the Clean Air Projects K-12 website had received more than 7,600 unique visitors. The
center's educational efforts help students, educators, and other stakeholders think critically about air quality and health.
As a result, the community has been empowered to make informed decisions about these issues.
Two toolkits for childcare providers - an Integrated Pest Management flPM) Toolkit and a Green Cleaning and Sanitizing
Toolkit - were developed by the UC Berkeley (CERCH) Children's Center and the UC San Francisco Childcare Health
¦| - Program.®'10 They provided environmental health training to schools and child care centers, in partnership with EPA
£ g Region 9 and the Pediatric Environmental Health Specialty Units. The UC Berkeley (CERCH) Center also developed an
CQ
^ ~ IPM training program for pest control companies serving schools and child care centers. The course is now a permanent
Continuing Education curriculum on the UC Statewide IPM program, and more than 1,160 pest control professionals
have been trained (as of 2017)."
62
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"i would not
consider it outreach
it is a dialogue; it
is a community
partnership."
- Dr. Elaine Faustman,
Director, University of
Washington Children's
Center.
Through their interactive web tool, the Dartmouth College Children's Center disseminates tips for reducing arsenic
exposure and preventing adverse health effects. Some of the tips include choosing white rice over brown rice,
substituting rice with other grains such as millet and quinoa, soaking and rinsing rice before cooking, limit apple juice or
choose other juices, reading food labels closely to avoid sweetener in the form of brown rice syrup, and testing private
wells for arsenic levels.3
WATER
W you gvt your drinlclntg
wtHe from ft private will,
you should have your water
t**4*d for wwttlc. EPA
regulations and testing on9y
upply to public w«4*r
source*, not private wells.
Images from, the Dartmouth College Children's Center's web too on arsenic.
VI &&
RICE
Rke ptanEs readily fake
up	pww in
vo«l and water.
APPLES
Applet can contain
an»nk (iwn toll or
water corrtwnlreafclon.
63
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BACKGROUND
The Children's Centers have developed technologies and used existing methods in new ways to more accurately measure
environmental exposures in the places where children spend most of their time. These accurate and creative assessment
tools can reveal correlations between environmental exposures and disease outcomes that are missed by conventional
methods. The Children's Centers have collected biological and environmental samples across multiple years, allowing for
analysis of between- and within-person variability. Between-person variability means comparing the levels of chemicals
in different people. Within-person variability means comparing the levels of chemicals in the same person across seasons
and years. It also allows for identification of seasonal and long-term trends. Whether it is measuring new contaminants or
mixtures of contaminants, improving sampling techniques, or developing new exposure models, the exposure assessment
conducted by the centers allows researchers to observe connections between complex environmental exposures and health
outcomes not previously seen.
The UC Berkeley (CERCH) Children's Center has pioneered methods to measure manganese exposure in children's
teeth.13'While manganese is an essential nutrient, it is also used in some pesticides, and studies indicate that high
¦| - exposures during development can result in neuropsychological deficits in children.12 Studies addressing health effects
I « of manganese during prenatal development are hampered by a lack of maternal biomarkers that reflect fetal exposure.
CO
^ w Teeth accumulate metals, and their growth proceeds in an incremental pattern similar to growth rings that span the
prenatal and postnatal periods. Measuring the distribution of manganese in children's teeth allows researchers to
reconstruct exposure to manganese-containing pesticides at specific times during fetal development.13
The ability to accurately capture children's air pollution exposures is essential to understanding its relationship to
asthma. Many studies have focused on exposure to fine particulate matter (PM,S3 as a risk factor for asthma, but very few
epidemiological studies have assessed the implications of exposure to ultrafine particulate matter (UFP). Traditionally,
monitoring UFP has been limited by the cost, size, weight, and upkeep of the equipment. However, Thejohns Hopkins
University Children's Center used a monitor that is small enough for personal exposure assessment resolution (Partector,
CH Technologies). Measuring UFP along with PM and the use of a GPS receiver improves the ability to observe
relationships between air pollution and asthma by recording exposure peaks in relation to time and space. The center
captured personal exposures at home, school, and in transit by placing these monitors in children's backpacks as they
went about their daily activities. This is critical since ambient monitors often used in exposure assessments cannot
capture the indoor environments where children spend most of their time.
64
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The Denver Children's Center has improved the accuracy of measuring air
pollution exposure with innovative, wearable exposure monitor sampiers.
These samplers are used to measure coarse particulate matter (PM!D) and
its components, including black carbon, brown carbon, and secondhand
tobacco smoke. Children wear the samplers along with ozone and nitrogen
dioxide passive badges during the school week. Analyses have shown that
personal monitors measure respirabie pollutant exposures more accurately
than conventional stationary monitors, As a result, the personal monitors
reveal correlations between asthma severity and air pollutant exposures that
are missed by stationary monitors. Understanding the relationship between
exposures and asthma severity at the personal ievel is critical for managing	n
1	J	1	o o	Personal wearable exposure monitors:
asthma symptoms and for developing effective interventions and therapies.	MicroPEM™ and ogawa™ badges.
o
(D
3
<
fD
The UC Berkeley (CERCH) Children's Center has partnered with Oregon State
University to use silicone sampling bracelets to assess pesticide exposures.
These bracelets monitor cumulative pesticide exposures during daily
activities, both indoors and outdoors. This approach differs from stationary
monitors that can miss important exposure events and result in incomplete
measurements. This is one of the first studies to compare measurements
of pesticides in the bracelets to pesticides measured in house dust and
agricultural pesticide use.
MyExposome wristband monitor.
65
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«
INTERDISCIPLINARY APPROACHES
BACKGROUND
The Children's Centers approach pressing questions with a wide-angle lens from multiple dimensions, while not allowing
the boundaries of any particular field to restrict, define, or determine the array of possible solutions. Experts from across
many fields are involved at the earliest stages of developing research hypotheses, and they have been essential in narrowing
the gap among environmental health knowledge and its application in our daily lives. Whether it is the synergy between
the Emory University's nursing, medicine, arts and sciences, and public health programs, the University of Michigan's
collaboration with a medical anthropologist to study neighborhood characteristics, or partnerships between the University of
Illinois and the Pediatric Environmental Health Specialty Units (PEHSUs), the Children's Centers leverage the unique expertise
of many fields to provide evidence to protect our children.
The maternal-infant microbiome study at the Dartmouth College Children's Center has fostered interdisciplinary research
that was not realized prior to this program. This collaboration involves maternal-fetal physicians, neonatologists,
pediatricians, experts in bioinformatics and statistics, biologists, ecologists, microbiologists, epidemiologists, and
toxicologists to structure a pipeline from the clinic to the lab, to the analytics/visualization, and back to clinical outcomes.
Additionally, this center is applying elemental mapping, which is an analytical technique in geochemicai, environmental,
and materials sciences that has only recently been applied to epidemiological studies. This approach can be used to
investigate biomarkers and provide mechanistic information, and to investigate the impact of environmental toxins
in combination with measures of socioeconomic adversity. These novel approaches facilitate collaboration between
behavioral scientists, physicians, neonatologists, and pediatricians.
The University of Washington Children's Center translated research from public health, medicine, and public affairs
to answers questions on how, what, where, and when agricultural farmworkers and their families are exposed to
pesticides. The center worked with biologically based models for systems biology, in vitro models for evaluating impacts
on neurodifferentiation, animal models for neurobehavior, exposure scientists, and engineers for air and fugitive dust
modeling as well as risk assessors.
66
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"Such centers are
critical generators of
new knowledge and
also incubators for
the next generations
of leaders in children's
environmental
health."
- Textbook of Children's
Environmental Health.1®
Developmental psychologists view the eyes as a window into an infant's world. By studying infant looking behavior,
researchers have iearned a great deal about early cognitive development. However, this approach is labor intensive
because it typically involves manually scoring behavior as infants view stimuli on a computer screen. An important goal
of the University of Illinois Children's Center is to adapt and implement methods used by developmental psychologists,
allowing them to better study cognitive development during infancy in the epidemiological setting. To achieve this goal,
the center partnered with an engineering research group and developed a new software that uses a computer webcam
to reliably detect and record the gaze direction ofvery young infants (1 to 5 weeks of age). This allows for automated
assessments of visual attention and visual recognition memory. Previous methods to track looking behavior cannot be
used in infants this young, so this new methodology is a breakthrough in the field of children's health. This advancement
would not be possible without the kind of interdisciplinary collaboration that is at the heart of the Children's Centers
philosophy.
The University of Michigan Children's Center spans various disciplines in public health. For example, the center is working
with a medical anthropologist to examine how neighborhood characteristics, sleep patterns, perceptions of water quality,
and diet may interact with toxicants to affect health outcomes. The health outcomes include growth and maturation,
telomere length (often a sign of aging and/or stress), and DNA methylation profiles in a longitudinal birth cohort in Mexico
City. Due to this collaboration, the center has revised many of their questionnaires and research activities to be culturally
relevant and to reflect the daily lives of participants.
67
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NEW METHODS AND TECHNOLOGIES
DACKGROUND
The Children's Centers have pioneered new approaches to study environmental exposures and health outcomes to establish
a strong base of science. Novel methodologies, instrumentation, technologies, and tools have been used to more accurately
measure and characterize complex exposures and identify early endpoints that are predictive of disease outcomes. Novel
approaches to understand the biology of diseases include what are referred to as "-omics", such as genomics, epigenomics,
proteomics, adductomics, metabolomics, and microbiomics. By incorporating these innovative methods, the Children's
Centers have helped to revolutionize research and clinical practice. Ushering in new paradigms allow for more precise
measurement and discovery of new risk factors.
>1
SB
v —I
iS	u
tu	a,
as	c
u	—
z>
Since the 1970s, blood spots have been routinely collected from every child at birth
and stored for future reference. UC Berkeley (CIRCLE) Children's Center researchers
obtained authorization from the California Department of Public Health to access
this extensive archive as a valuable resource for discovering early-life exposures
that may contribute to disease. By developing and validating new omics techniques,
researchers have used biood spots to study the risks of childhood leukemia.
These methods measure chemicals extracted from the blood spots, namely, small
molecules (metabolomics) and adducts of reactive chemicals with human serum
albumin (adductomics).'7*®3 Unlike traditional, hypothesis-driven methods that target
individual exposures, metabolomics and adductomics focus on broad classes of
molecules. Investigators are comparing metabolomic and adductomic profiles
between children with and without leukemia in order to find discriminating features
that will then be investigated to determine their chernicai identities and exposure
sources. This novel untargeted approach will allow for discovery of new risk factors
for childhood leukemia.
Blood spots that are routinely
collected from every child at birth.
The Duke University Children's Center developed a model to examine the effects of specific environmental aexposures
on the brain. This in vitro model helps researchers study environmental exposures and neurodevelopmental health
outcomes using primary neural stem cells derived from the neonatal rat brain, which closely resembles the human brain.
The center is currently studying exposure of these cells to tobacco smoke extract and its constituents, including nicotine,
and testing nutritional supplements for the potential to lessen tobacco-induced health effects.
68
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"Children's Centers
have led to an improved
understanding of the
environmental impacts
on child health and
development."
- 2017 National Academy
of Sciences Report,22
One novel approach used to study central nervous system integrity with infants is by using a custom pacifier device to
examine non-nutritive suck patterning. This can serve as a potential biomarker of infant brain injury and be used as a
prognostic tool for detecting future developmental delays. The Northeastern University Children's Center is using non-
nutritive suck patterning to examine the effect of chemical exposures during pregnancy on the infant brain. This will be
the first time it has been used in environmental health sciences.
As a leader in epigenetics, the University of Michigan Children's Center is employing both gene-specific and genome-wide
approaches to identify toxicant- and diet-induced perturbations to DNA methylation and gene expression underlying
adverse health outcomes. Exposures to lead, bisphenol A (BRA), and phthalates at multiple developmental stages
(prenatally, early childhood, and pre-adolescence) are associated with blood leukocyte methylation. This suggests that
environmental exposures can impact the epigenome during multiple stages of life.3';41The epigenome is made up of
chemical compounds that can tell genes what to do. Further, lipids in the maternal bloodstream are associated with
epigenetic programming in infants,3®
The University of Washington Children's Center has developed advanced mathematical models to estimate between-
and within-person variability. They also developed a biokinetic mode! for Cortisol. The center has linked parent
organophosphate (OP) pesticide compounds in the blood with concentrations in house dust and calculated observed
half-lives of parent compounds in the blood.2®7 These advanced methodologies put the observed exposures in context.
Incorporating MRI brain imaging into epidemiological studies aiiows researchers
to examine changes to brain structure that may mediate the effects of air
pollution exposure on a range of neurodevelopmental, behavioral, and physical
outcomes. Researchers have documented associations between specific brain
changes and prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) and
chiorpyrifos, suggesting a key pathway for the observed neurotoxic effects of
these chemicals.
MRI scans from the Columbia University Children^
Center study population.show correlations of prenata
PAH levels with cerebral surface, measures?^
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69
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POPULATION-BASED STUDIES
BACKGROUND
Cohort studies follow a designated study population over time to establish risk factors for disease. Prospective cohort
studies that are designed to follow children from before birth into adolescence or adulthood can provide critical information
on prenatal and early childhood determinants of adult disease. The plasticity of the brain during puberty is the same as the
first three months of life, and it is important to observe children during both these phases of development. Many Children's
Centers have initiated large observational, prospective cohort studies that start during pregnancy or immediately after
birth, then follow the children up to young adulthood. Other Children's Centers have utilized cohorts funded through other
mechanisms, leveraging major investments that have already been made, such as examples shown below for the Duke
University and the University of Michigan Children's Centers.
Starting in 1998, the Columbia University Children's Center enrolled more than 700 Latina and African-American women
from New York City for its Mothers and Newborns (MN) cohort. This initial study led to the enrollment of subsequent
cohorts, including 130 younger siblings of the MN cohort participants and the Fair Start cohort, that is currently enrolling
pregnant women from the same neighborhoods. These prospective cohort studies are examining the impact of prenatal
and postnatal exposure to air pollution, bisphenol A (BRA), phthalates, fiame retardants, and pesticides on childhood
health and development. These studies have been instrumental in the field, finding associations between certain
environmental exposures and multiple adverse outcomes including reduced birthweight, obesity, attention-deficit
hyperactivity disorder (ADHD), reduced IQ, and anatomical brain changes. The research has also revealed interactions
between toxicant exposure and stressors related to poverty.
The University of Washington Children's Center has enrolled and maintained a prospective cohort of farmworkers,
nonfarrnworkers, and their families living in Yakima Valley, Washington. Families were first enrolled in the study when the
children were between ages 2 and 6 years. Over the next 10 years, researchers assessed pesticide exposure in multiple
seasons by measuring levels of pesticides in dust, urine, and blood. The study has also assessed biological mechanisms
linked with toxicity and disease. A hallmark of this cohort is the frequency of samples, taken multiple times per season,
during multiple seasons per year, across multiple years. This structure has allowed researchers to evaluate between- and
within-person variability across seasons and years. One unique element of this study is the extensive exposome-based
assessments. Not only have researchers measured over 80 pesticides in dust, they have also assessed phthalates,
metals, mold, and social stress exposures using biomarkers and questionnaires.
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"The Children's Centers have
overcome many hurdles
to understand the links
between environmental
exposures and health
outcomes or social and
cultural factors. Long-
term studies [are critically
important] to assess the
full range of developmental
consequences...at different
life stages."
- Excerpt from Lessons learned for
the National Children's StudyP
The Duke University Children's Center follows a subset of approximately 400 children from a pre-existing Newborn
Epigenetics STudy (NEST) cohort. NEST includes 2,000 racially-diverse pregnant women in central North Carolina, and was
specifically designed to allow for in-depth investigation of epigenetic mechanisms that link the prenatal environment to
children's health outcomes. NEST has assembled a rich repository of biological specimens over time from these mothers
and their children as well as medical and epidemiological data that altogether have provided a strong foundation for
other studies, including the Duke University Children's Center. This center is specifically investigating how secondhand
tobacco smoke exposure during early life increases the risk of developing ADHD during adolescence.
The Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort consists of children enrolled at
birth in Mexico City beginning in 1994 and followed for more than 22 years. The previously funded cohort is now
part of the University of Michigan Children's Center, which investigates the influence of lead exposure on fetal and
infant development. Findings from ELEMENT have found relationships between prenatal iead and low birthweight,®
lower weight and higher blood pressure in young gfrfefl® cognition,3336 and ADHD37; findings have also shown that
calcium supplementation during pregnancy can blunt the mobilization of lead stored in bone, thereby reducing fetal
exposure;38140 Over the long follow-up period, researchers have been able to study exposures to metals other than lead,
including fluoride,41 cadmium,42 mercury;43-BPA, and phthalates.^* Studies on additional health outcomes, such as
cognition,5®-® behavior,dental health, sexual maturation,46"w^diposlip*4®® and cardiometaboiic risk58 have also
been possible. Evidence from ELEMENT has informed U.S. and Mexican lead exposure guidelines, including the 2010
CDC "Guidelines for the Identification and Management of Lead Exposure in Pregnant and Lactating Women", among
others.5^
In addition to the CHARGE study, the UC Davis Children's Center launched a second epidemiologic study of autism
spectrum disorder (ASD) in 2006. The Markers of Autism Risk in Babies - Learning Early Signs (MARBLES) study
follows mothers with at least one child with ASD before, during, and after their pregnancy. This allows researchers
to obtain information about babies' prenatal and postnatal exposures. Infants are enrolled at birth and assessed for
neurodevelopmental status until 3 years old. MARBLES has enrolled over 440 mother-child pairs and has conducted
longitudinal biological and environmental sampling.
71
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i
s:


RODENT MODELS
DACKGROOND
V >

MLif
Determining what chemical exposures are toxic to children requires a variety of research approaches, including high
throughput in vitro cell based assays, animal models, and clinical and epidemiological studies. Studying mice in particular
allows researchers to mimic how environmental exposures might affect humans. Such animal models provide invaluable
information that researchers can use to isolate what chemicals pose the greatest risks, work out the complex mechanisms
of toxicity, determine who is at risk for disease, and develop effective treatments. The Children's Centers use animal models
alongside epidemiological studies to inform actions designed to reduce the burden of disease in children.
Animal studies from the University of Illinois Children's Center were the first to determine the long-term and
transgenerational consequences of prenatal phthalate exposure on both male and female reproduction. Prenatal
exposure to phthalates was found to disrupt several aspects of female reproduction, including a disrupted estrous
cycle, ovarian cysts, increased uterine weight, reduced fertility, and direct damage to the ovaries,6®151 The chemical
mixture used in these animal studies was based on the specific mixture of phthalates identified in the blood of pregnant
women enrolled in the center's cohort study. The resulting data represent the first findings from animal studies using an
environmentally relevant phthalate mixture.
Researchers found that exposure to bisphenol A (BPA) during perinatal development and adolescence may alter neuron
and glia numbers in the prefrontal cortex of adult rats.62 Given that the prefrontal cortex is a part of the brain that is
critical for learning and memory, changes to the structure and function of this region may have broad implications for
health. Studies are also underway to explore the effects of an environmentally relevant mixture of phthalates on the
prefrontal cortex. Early findings show that phthalates resulted in impaired cognitive flexibility in adult rats. Researchers
have taken anatomical measurements of the prefrontal cortex of the rat brain to establish the neural basis for this
deficit.®
Researchers used animal models to investigate the epigenetic mechanisms or ways that polycyclic aromatic
hydrocarbons (PAHs) and BPA may affect neurodevelopment and obesity.®*^ High prenatal PAH exposure was found
to be associated with weight gain and greater fat mass in mice, as weil as more sedentary behaviorsf^These results
parallel the findings in epidemiological studies linking high prenatal PAH exposure with higher risk of childhood obesity.68
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"We don't do advocacy.
We conduct the science
and provide it in a way
that can empower both
the communities and
the policymakers to do
something about it."
- Frank Gilliland, Director,
University of Southern
California Children's Center.
An animal model was used to examine the effects of preconception, prenatal, and early childhood
exposure to tobacco smoke extract and nicotine on neurobehaviorai function. Researchers successfully
differentiated between the effects of exposure to the complex tobacco mixture and to nicotine alone. These
investigators found predominant persistent neurobehaviorai Impairments with late gestational exposure.
However, persisting neurobehaviorai effects were also seen with early gestational and even preconceptional
exposure,® Studying rats allows researchers to analyze effects of exposures that are difficult to study in
humans, particularly in different parts of the brain. Because the effects of prenatal exposure in children is
usually studied using blood, the genes identified in animals help to determine where researchers should
look for similar epigenetic alterations in humans.
Researchers are utilizing an agouti mouse model to mirror exposures seen in humans. They are investigating the role
of perinatal and peripubertal iead, BRA, and phthalate exposures on offspring lifecourse metabolic status, reproductive
development, and epigenetic gene regulation. Findings show that perinatal lead exposure in mice was associated with
increased food intake, body weight, total body fat, energy expenditure, and insulin response in adult mice, with more
pronounced effects in males;70 In addition, lead exposure immediately before or after birth (perinatal) was associated
with changes to gut microbiota that can cause obesity. Perinatal lead exposure also enhanced long-term epigenetic drift
in mice.71'7®1
Using animal models, researchers have conducted neurobehaviorai studies to identify how genetic differences and
timing of exposure modifies the health effects of pesticide exposure. The use of in vitro models that mimic brain
development shows the impact of pesticides on signaling pathways and brain disorders, in vitro and animal models have
demonstrated that organophosphate (OP) pesticides significantly inhibited neural growth, even at low concentrations.
These effects appeared to be mediated by oxidative stress, as they were prevented by antioxidants.7&7SThese results
suggest potential mechanisms where OP pesticides may interfere with neurodevelopment in children. Understanding
these mechanisms may help identify critical windows of susceptibility in children.
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BACKGROUND
Biological samples such as blood, placenta, urine, baby teeth, hair, and saliva allow
researchers to answer questions about environmental exposures over long periods
of time. The Children's Centers have been collecting and storing such samples since
the inception of the program in 1997. As new environmental exposures of concern
are identified, these samples serve as invaluable resources regarding historical
exposures and health outcomes (as demonstrated by the Cincinnati Children's
Center example below). Epidemiological studies, such as those established and
accessed by the Children's Centers, are more valuable when there is capacity to
store samples for future analysis. Evolving approaches for processing, extracting,
and storing samples allow for downstream high throughput laboratory analyses at a
pace not previously considered possible.
220,000
biological and
environmental *
samples
collected by
the UC Berkeley
(CERCH) Children's
Center since 1998.

The Cincinnati Children's Center has utilized archived samples to examine the effects of chemicals that were not included
in its original study design. At its inception, the center focused on the effects of lead, pesticides, mercury, polychlorinated
biphenyls (PCBs), and tobacco smoke. As time went on, however, community and public health concerns emerged
concerning the potential effects of other metals, bisphenol A (BRA), polybrominated diphenyl ethers (PBDEs), phthalates,
and other metals on the health of children. Under a different grant, Cincinnati Children's Center researchers were able
to test for the presence of these chemicals in the stored biological samples and explore the associations between past
exposures and health outcomes.
The UC Davis Children's Center has amassed an enormous repository of biological and environmental samples.
More than 200,000 samples, including urine, blood, saliva, hair, baby teeth, placenta, maternal vaginal swabs, breast
milk, meconium, and stool samples are now stored In the center's biorepository. Records of this biorepository will be
available online where potential collaborators may query.
Since 1998, the University of Washington Children's Center has maintained a biorepository of biological and
environmental study samples. These samples were leveraged by the National Children's Study for formative research
projects related to social stress, dust pesticide concentrations, and characterization of the impacts of pesticides on the
oral microbiome.7»TSamples have also been used to quantify the microRNA signal associated with pesticide exposure
and occupational status.74
74
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"Solid intervention work has been created [by the Children's Centers] along
with extended links to the communities served. The continuity of this work has
proven successful and should be maintained."
- EPA Board of Scientific Counselors/Children's Health Protection Advisory Committee Review.79
Starting in 1998, the UC Berkeley (CERCH) Children's Center established an extensive biorepository of more than 220,000
biological and environmental samples from the CHAMACOS studies. The center has collected urine samples from	c
hundreds of children, starting as young as 6 months old;8® These urine collection protocols have been adopted by cohort £ £
o
studies nationally and around the world. The center has pioneered blood processing and storage techniques and has	i »
w fD
collected breastmilk, saliva, hair, and deciduous (baby) teeth. Collecting samples from children at very young ages allows
researchers to assess the effects of early life exposures on health outcomes later in childhood and young adulthood.
The Dartmouth College Children's Center has applied innovative approaches and technologies to expand infant
microbiome studies to large scale, molecular epidemiology studies of healthy pregnant women and their infants. The
center uses state-of-the-art laboratory techniques including automated archival storage and retrieval, and automated
specimen processing. Expanding the application of advanced microbial sequencing and bioinformatics techniques has
furthered the investigation of environmental exposures, the developing microbiome, and health outcomes.
EPA-funded research grants adhere to all laws, regulations, and policies supporting the ethical conduct and regulatory
compliance of protecting the rights and welfare of human subjects and participants in research. To learn more about EPA's
protection of human subjects, visit https://www.epa.gov/osa/basic-information-about-human-sijbiects-research-0.
75
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INDEX
A
Agriculture 21, 29, 52
Air pollution see also indoor air pollution
and traffic-related air pollution
(TRAP) 20,21,22,23,27,30,
31,32, 33, 38, 39, 40, 60, 64, 65,
69, 70
Asthma 20, 21
Autism 30, 31
Birth outcomes 22, 23
Immune function 27
Obesity 32, 33
Animal models see also rodent models
66, 72, 73
Anxiety 28, 29
Arsenic 23,28,42,43,60,63
Birth outcomes 23
Asthma 2, 3, 20, 21, 26, 27, 32, 38, 39,
40, 56, 57, 61, 62, 64, 65
Air pollution 38, 39, 40
Obesity 32
Secondhand tobacco smoke 56, 57
Attention-deficit/hyperactivity disorder
(ADHD) 28,29,51,52,70,71
Lead 51
Pesticides 52
Autism 2, 3, 26, 29, 30, 31, 39, 53, 71
Immune function 26
B
Behavior 3, 26, 27, 28, 29, 30, 31, 40,
46, 50,51,52, 67, 69,71,72
Aggression 28
Criminal 50, 51
Self-control 28
Biomarkers 32, 48, 56, 64, 66, 70
Biorepository 74, 75
Birth cohorts see also cohorts and
population-based studies 53,
67
Birth defects 22, 39
Air pollution 39
Birth outcomes see also birth defects;
low birthweight; and preterm
birth 22,23,42,48
Arsenic 42
Phthalates 48
Bisphenol A (BPA) 21, 29, 32, 33, 44, 45,
48, 69, 70,71,72, 73, 74
Obesity 32, 33
Body Mass Index (BMI) 32,44
Brain development see also
neurodevelopment 26,28,29,
31,48, 49, 53, 73
Brown University Children's Center 108
C
Cancer see also leukemia 3, 24, 25, 26,
27,	28, 29, 38, 56
Immune function 26,27
Secondhand tobacco smoke 56
Case-control study 31
Center for the Health Assessment of
Mothers and Children of Salinas
(CHAMACOS) 53,61,75
Centers for Disease Control and
Prevention (CDC) 50,62,71
Childhood Autism Risks from Genes and
Environment (CHARGE) 31,71
Cincinnati Children's Center 33, 44, 46,
50, 51, 74, 108
Clean Air Act 38, 51
Cohort study see also population-based
studies 28, 53, 67, 70, 71, 72,
75
Columbia University Children's Center
28,	29, 33, 38,40, 41,44, 46, 53,
55, 69, 70, 71
Community outreach 60,62
Consumer products see also
bisphenol A (BPA); phthalates;
polybrominated diphenyl ethers
(PBDEs) 44, 45, 46, 48
D
Dartmouth College Children's Center
23,42,43, 60, 63, 66, 75, 110
Denver Children's Center 62,65,110
Depression 28, 29
Developmental delay 28, 29, 30, 31, 49,
69
Diabetes 27, 32
Diet 25, 32, 42, 43, 52, 67, 69
Arsenic 42,43
Cancer 25
Duke University (NICHES) Children's
Center 51, 57, 68, 70, 71, 73,
111
Duke University (SCEDDBO) Children's
Center 111
Dust 25, 29, 46, 48, 49, 65, 66, 69, 70,
74
E
Emory University Children's Center 23,
66,111
Endocrine disrupting chemicals (EDCs)
32
Epigenetics 21, 26, 27, 69, 71, 72, 73
Exposure Assessment 41,64
F
Food 23, 42, 43, 44, 48, 51, 52, 60, 63,
73
Arsenic 42,43
Bisphenol A (BPA) 44
Pesticides 52
Phthalates 48
77
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INDEX
Food and Drug Administration (FDA) 43
G
Genetics 2, 24, 25, 30, 32, 53, 56, 73
H
Harvard University Children's Center
112
High-efficiency particulate air (HEPA)
filters 21,40, 57
I
Immune 3, 21, 25, 26, 27, 38, 41, 42, 43,
52
In utero 30, 42
In vitro 57, 66, 68, 72, 73
Indoor air pollution 21, 29, 32, 48
Neurodevelopment 29
Obesity 32
Integrated pest management (IPM) 55,
62
Interdisciplinary 66, 67
Intervention 12, 13, 15, 21, 27, 29, 32,
33, 39, 40, 54, 55, 57, 60, 65, 75
L
Laboratory 12, 32, 74, 75
Language 29, 50, 60
Lead 28, 29, 50, 51,61, 69, 71, 73, 74
Neurodevelopment 28, 29
Leukemia 2, 24, 25, 26, 27, 53, 56, 57,
62, 68
Immune function 26,27
Pesticides 53
Secondhand tobacco smoke 56, 57
Low birth weight 22, 38, 39, 53
78
Air pollution 38, 39
Lung development 38,39
Lung function 20,21,27,38,39,40
M
Maternal exposure 22
Metabolic 3, 27, 32, 33, 35, 44, 73
Microbiome 66,74,75
Mount Sinai School of Medicine
Children's Center 35,113
N
Neurobehavior 45, 47, 51, 66, 73
Neurodevelopment 25, 26, 27, 28, 29,
30, 39, 56, 57, 68, 69,71,72, 73
Cognition 28, 29, 40, 47, 50, 51, 52,
53, 67, 71, 72
IQ 3,26,28,29,46,50,51,52,53,
70
Memory 29, 52, 67, 72
Test scores 28, 29, 51, 52
Nitrogen dioxide (N02) 20, 32, 38, 40,
65
Northeastern University Children's
Center 69,113
0
Obesity 32, 33, 44, 45, 70, 72, 73
Bisphenol A(BPA) 44,45
Occupational exposure 24,30,31
Organophosphates (OPs) see also
Pesticides 21,22,30, 52,69,73
Ozone 20, 22, 23, 38, 65
P
Particulate matter (PM) 20, 32, 38, 40,
64, 65
Paternal exposure 24, 56
Pediatric Environmental Health Specialty
Unit (PEHSU) 62, 66
Pesticides see also organophosphates
(OPs) 21,22,23,24,25,28,29,
30, 42, 52, 53, 54, 55, 61, 65, 66,
69, 70, 73, 74
Autism 30, 31
Birth outcomes 22, 23
Cancer 24, 25
Chlorpyrifos 29, 30, 53, 69
Neurodevelopment 28, 29
Take-home pathway 54, 55
Phthalates 22, 23, 29, 31, 32, 33, 35, 45,
48,49, 69, 70, 71,72, 73, 74
Birth outcomes 22, 23
Neurodevelopment 29
Obesity 32, 33
Reproductive development 35
Polybrominated diphenyl ethers (PBDEs)
23, 25, 26, 29, 35, 45, 46, 47, 74
Birth outcomes 23
Cancer 25
Immune function 26
Reproductive development 35
Polychlorinated biphenyls (PCBs) 25,
26, 74
Cancer 25
Immune function 26
Polycyclic aromatic hydrocarbons (PAHs)
20,21,24,25, 27, 28, 29, 32,40,
41, 69, 72
Asthma 20, 21
Cancer 24, 25
Immune function 27
Neurodevelopment 28, 29
Obesity 32
Population-based studies see also case-
control study and cohort study
70
Preconception 9,15, 24, 73
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INDEX
Prenatal 9, 21, 22, 23, 25, 26, 27, 28, 29,
32, 33, 35, 39, 40, 42, 44, 45, 46,
47,48, 50, 52, 53, 56, 57,61,64,
69, 70,71,72, 73
Air pollution 39,40
Arsenic 42
Asthma 21
Birth outcomes 22, 23
Bisphenol A(BPA) 44,45
Cancer 25
Immune function 26,27
Lead 50
Neurodevelopment 28, 29
Obesity 32, 33
Pesticides 52, 53
Phthalates 48
Polybrominated diphenyl ethers
(PBDEs) 46, 47
Reproductive development 35
Secondhand tobacco smoke 56, 57
Preterm birth see also birth outcomes
22, 23, 39, 41,56
Air pollution 39,41
Secondhand tobacco smoke 56
Puberty 35,45, 70,73
R
Reproductive 35, 44, 45, 48, 61, 72, 73
Bisphenol A (BPA) 44,45
Phthalates 48
Respiratory 2, 21, 25, 38, 41, 42, 56, 57
Air pollution 38,41
Arsenic 42
Asthma 21
Secondhand tobacco smoke 56, 57
Rural 21,42
S
School 20, 28, 31, 39, 47, 51, 54, 55, 57,
60, 62, 64, 65
Secondhand tobacco smoke 20, 32, 33,
56, 65, 71
Asthma 20
Obesity 32, 33
T
Take-home pathway 54, 55
Thejohns Hopkins University Children's
Center 21,32,38,40,57, 64,
112
Traffic-related air pollution (TRAP) 20,
30, 39
Asthma 20
Autism spectrum disorder (ASD) 30
U
University of California, Berkeley
(CERCH) Children's Center see
also CHAMACOS 21, 22, 23, 35,
44, 45, 46, 47, 49, 52, 53, 54, 61,
62, 64, 65, 74, 75,114
University of California, Berkeley
(CIRCLE) Children's Center 24,
25,26, 56, 57, 62, 68,115
University of California, Berkeley/
Stanford University Children's
Center 20,21,22,27,39,41,
114
University of California, Davis Children's
Center see also CHARGE 26, 27,
29, 30,31,49, 60, 71,74, 115
University of California, San Francisco
Children's Center 60,61,62,
116
University of Illinois Children's Center
33, 45, 48, 66, 67, 72, 11 6
University of Iowa Children's Center 21,
117
University of Medicine and Dentistry of
Newjersey Children's Center
117
University of Michigan Children's Center
20, 22, 32, 33,35, 44, 48,51,66,
67, 69, 70, 71,73, 118
University of Southern California
Children's Center 20,22,30,
31,32, 33, 38, 39, 40, 57, 60, 73,
118
University of Washington Children's
Center 45, 52, 54, 55, 60, 63,
66, 69, 119
Urban 23,28,33
W
Water 42,43,44, 51, 60, 67
Arsenic 42,43
Bottles 44
Lead 51
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REFERENCES
CHILDREN'S HEALTH MATTERS
1.	Giddings BM, Whitehead TP, Metayer C and Miller MD. (2016). Childhood leukemia incidence in California: High and rising in
the Hispanic population. Cancer, 122(18), 2867-2875. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/cncr.3Q129/
abstract
2.	Centers for Disease Control and Prevention. Asthma surveillance data. 2016; Available from: https://www.cdc.gov/asthma/
asthmadata.htm
3.	Christensen DL, BaioJ, Braun KV, Bilder D, CharlesJ and al. e. (2016). Prevalence and characteristics of autism spectrum
disorder among children aged 8 years — Autism and developmental disabilities monitoring network, 11 sites, United States.
MMWR Surveill Summ, 65(No.SS-3), 1-23. Retrieved from https://www.cdc.gov/mmwr/volumes/65/ss/ss6503a1.htm
4.	Trasande L, Malecha P and Attina TM. (2016). Particulate matter exposure and preterm birth: Estimates of US attributable
burden and economic costs. Environmental Health Perspectives, 124(12), 1913-1918. Retrieved from https://ehp.niehs.nih.
gov/15-10810/
5.	Centers for Disease Control and Prevention. Lead. 2017; Available from: https://www.cdc.gov/nceh/lead/
6.	World Health Organization. Global plan of action for children's health and the environment (2010-2015). 2010; Available
from: http://www.who.int/ceh/cehplanaction10 15.pdf
7.	HallmayerJ, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, et al. (2011). Genetic heritability and shared
environmental factors among twin pairs with autism. Archives of General Psychiatry, 68(11), 1095-1102. Retrieved from
http://jamanetwork.com/journals/jamapsychiatry/fullarticle/1107328
8.	World Health Organization. Don't pollute my future! The impact of the environment on children's health. 2017; Available
from: http://apps.who.int/iris/bitstream/10665/754678/1/WHQ-FWC-IHF-17.01-eng.pdf
9.	Trasande L and Liu Y. (2011). Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion
in 2008. Health Affairs, 30(5), 863-870. Retrieved from http://content.healthaffairs.Org/content/30/5/863.long
10.	Science and Environment Health Network. (2010). The price of pollution: Cost estimates of environment-related childhood
disease in Michigan, http://www.sehn.org/tccpdf/childnood%70illness.pdf
11.	US Environmental Protection Agency. (2015). Benefit and cost analysis for the effluent limitations guidelines and standards
for the steam electric power generating point source category, https://www.epa.gov/sites/production/files/2015-10/
documents/steam-electric benefit-cost-analvsis 09-29-2015.pdf
12.	Buescher AV, CidavZ, Knapp M and Mandell DS. (2014). Costs of autism spectrum disorders in the United Kingdom and
the United States. JAMA pediatrics, 168(8), 721-728. Retrieved from http://jamanetwork.com/joijrnals/jamapediatrics/
fullarticle/1879773
13.	JohnsonJ and Collman G. (2015). Letter to Children's Centers annual meeting participants.
14.	(1997). Exec. Order No. 13045, 62 FR 19885. https://www.gpo.gov/fdsvs/pkg/FR-1997-04-73/pdf/97-10695.pdf
15.	National Institutes of Health and US Environmental Protection Agency. RFA-ES-14-002: Children's Environmental Health
and Disease Prevention Research Centers (P50). 2014; Available from: https://grants.nih.gov/grants/guide/rfa-files/RFA-
FS-14-007.html
80
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REFERENCES
HEALTH OUTCOMES
1.	Centers for Disease Control and Prevention. National Center for Health Statistics: Asthma. 7017: Available from: https://
www.cdc.gov/nchs/fastats/asthma.htm
2.	Dockery D, Outdoor Air Pollution, in Textbook of Children's Environmental Health, P. Ladnrigan and R. Etzel, Editors. 2014,
Oxford University Press: New York, NY. p. 201-209.
3.	Centers for Disease Control and Prevention. Asthma in schools. 2017; Available from: https://www.cdc.gov/healthyschools/
asthma/
4.	US Environmental Protection Agency. Asthma facts. 2013; Available from: http://www.epa.gov/asthma/pdfs/asthma fact
sheet en.pdf
5.	Moorman J, Akinbami L and Bailey C. (2012). National Surveillance of Asthma: United States, 2001-2010. https://www.cdc.
gov/nchs/data/series/sr 03/sr03 035.pdf
6.	Centers for Disease Control and Prevention. Asthma in the US. 2011; Available from: https://www.cdc.gov/vitalsigns/asthma/
index.html
7.	McConnell R, Islam T, Shankardass K,Jerrett M, Lurmann F, Gilliland F, Gauderman J, et al. (2010). Childhood incident asthma
and traffic-related air pollution at home and school. Environmental Health Perspectives, 118(7), 1021-1026. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970907/
8.	Gauderman W, Avol E, Lurmann F, Kuenzli N, Gilliland F, PetersJ and McConnell R. (2005). Childhood asthma and
exposure to traffic and nitrogen dioxide. Epidemiology, 16(6), 737-743. Retrieved from https://www.ncbi.nlm.nih.gov/
pnbmed/16777167
9.	McConnell R, Berhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N, et al. (2006). Traffic, susceptibility, and childhood
asthma. Environmental Health Perspectives, 114(5), 766-772. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC1459934/
10.	Gale S, Noth E, Mann J, BalmesJ, Hammond S and Tager I. (2012). Polycyclic aromatic hydrocarbon exposure and wheeze in
a cohort of children with asthma in Fresno, CA. Journal of Exposure Science and Environmental Epidemiology, 22(4), 386-
392. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219412/
11.	Lewis TC, Robins TG, Mentz GB, Zhang X, Mukherjee B, Lin X, Keeler GJ, et al. (2013). Air pollution and respiratory symptoms
among children with asthma: vulnerability by corticosteroid use and residence area. Science of the Total Environment, 448,
48-55. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/73773373
12.	US Environmental Protection Agency. If you have a child with asthma, you're not alone. 2001; Available from: https://nepis.
epa.gov/Fxe/7vPDF.cgi/000007C7.PDF?Dockev=000007C7.PDF
13.	Butz A, Matsui E, Breysse P, Curtin-Brosnan J, Eggleston P, Diette G, Williams D, et al. (2011). A randomized trial of air
cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke
exposure. Archives of Pediatrics and Adolescent Medicine, 165(8), 741-748. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/71810636
14.	Schwartz D. (1999). Etiology and pathogenesis of airway disease in children and adults from rural communities.
Environmental Health Perspectives, 107(S3), 393-401. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC1566776/
15.	Raanan R, BalmesJR, Harley KG, Gunier RB, Magzamen S, Bradman A and Eskenazi B. (2015). Decreased lung function in
7-year-old children with early-life organophosphate exposure. Thorax, 71(2), 148-153. Retrieved from http://thorax.bmj.
com/content/71/7/148.long
16.	Raanan R, Harley K, BalmesJ, Bradman A, Lipsett M and Eskenazi B. (2015). Early-life exposure to organophosphate
pesticides and pediatric respiratory symptoms in the CHAMACOS cohort. Environmental Health Perspectives, 123(2), 179-
185. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314748/
81
-------
REFERENCES
HEALTH OUTCOMES
17.	Raanan R, Gunier RB, BalmesJR, Beltran AJ, Harley KG, Bradman A and Eskenazi B. (2017). Elemental sulfur use and
associations with pediatric lung function and respiratory symptoms in an agricultural community (California, USA).
Environmental Health Perspectives, 87007, 087007-1-8. Retrieved from https://ehp.niehs.nih.gov/ehp528/
18.	Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, BalmesJ and Tager I. (2010). Ambient air pollution impairs
regulatory T-cell function in asthma. Journal of Allergy and Clinical Immunology, 126(4), 845-852. e10. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/20920773
19.	LiuJ, Zhang L, Winterroth L, Garcia M, Weiman S, WongJ, SunwooJ, et al. (2013). Epigenetically mediated pathogenic effects
of phenanthrene on regulatory T cells. Journal ofToxicology, 2013(2013), 967029. Retrieved from https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC3606805/
20.	Matsui EC, Hansel NN, Aloe C, Schiltz AM, Peng RD, Rabinovitch N, Ong MJ, et al. (2013). Indoor pollutant exposures modify
the effect of airborne endotoxin on asthma in urban children. American Journal of Rrespiratory and Critical Care Medicine,
188(10), 1210-1215. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/74066676
21.	Hew K, Walker A, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth E, et al. (2015). Childhood exposure to ambient
polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clinical
and Experimental Allergy, 45(1), 238-248. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396982/
22.	Arth AC, Tinker S, Simeone R, Ailes E, Cragan J and Grosse S. (2017). Inpatient hospitalization costs associated with birth
defects among persons of all ages—United States, 2013. MMWR Morbidity and Mortality Weekly Report, 66, 41-46.
Retrieved from https://www.cdc.gov/mmwr/volumes/66/wr/pdfs/mm6602a1.pdf
23.	Centers for Disease Control and Prevention. Reproductive and birth outcomes. 2017; Available from: https://ephtracking.
cdc.gov/showRbBirthOutcomeEnv
24.	American Academy of Pediatrics Council on Environmental Health. (2012). Pediatric Environmental Health, Third Edition. Elk
Grove Village, IL.
25.	Centers for Disease Control and Prevention. Reproductive and birth outcomes. 2016; Available from: https://ephtracking.
cdc.gov/showRbLBWGrowthRetardationEnv.action
26.	Goldenberg RL, Culhane JF, lamsJD and Romero R. (2008). Epidemiology and causes of preterm birth. The Lancet,
371(9606), 75-84. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/18177778
27.	Padula AM, Noth EM, Hammond SK, Lurmann FW, Yang W, Tager IB and Shaw GM. (2014). Exposure to airborne polycyclic
aromatic hydrocarbons during pregnancy and risk of preterm birth. Environmental Research, 135, 221-226. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/25282280
28.	Padula AM, Mortimer KM, Tager IB, Hammond SK, Lurmann FW, Yang W, Stevenson DK, et al. (2014). Traffic-related air
pollution and risk of preterm birth in the San Joaquin Valley of California. Annals of Epidemiology, 24(12), 888-895. e4.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25453347
29.	Cossi M, Zuta S, Padula AM, Gould JB, Stevenson DK and Shaw GM. (2015). Role of infant sex in the association between air
pollution and preterm birth. Annals of Epidemiology, 25(11), 874-876. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4671488/
30.	Salam MT, MillsteinJ, Li Y-F, Lurmann FW, Margolis HG and Gilliland FD. (2005). Birth outcomes and prenatal exposure
to ozone, carbon monoxide, and particulate matter: results from the Children's Health Study. Environmental Health
Perspectives, 113(11), 1638-1644. Retrieved from http://www.ncbi.nlm.nih.gov/pijbmed/16763574
31.	US Environmental Protection Agency. (2013). Integrated Science Assessment for ozone and related photochemical oxidants.
https://www.epa.gov/isa/integrated-science-assessment-isa-ozone
32.	Ferguson KK, MeekerJD, Cantonwine DE, Chen Y-H, Mukherjee B and McElrath TF. (2016). Urinary phthalate metabolite
and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environment International, 94, 531-537.
Retrieved from http://www.sciencedirect.com/science/article/pii/S01604170163Q7318
82
-------
HEALTH OUTCOMES
REFERENCES
33.	Watkins DJ, Milewski S, Domino SE, MeekerJD and Padmanabhan V. (2016). Maternal phthalate exposure during early
pregnancy and at delivery in relation to gestational age and size at birth: A preliminary analysis. Reproductive Toxicology 65,
59-66. Retrieved from http://www.sciencedirect.com/science/article/pii/S089Q6238163016Q5
34.	Bradman A, Eskenazi B, Barr D, Bravo R, Castorina R, Chevrier J, Kogut K, et al. (2005). Organophosphate urinary metabolite
levels during pregnancy and after delivery in women living in an agricultural community. Environmental Health Perspectives,
113(12), 1802-1807. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16330368
35.	Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, et al. (2004). Association of in utero
organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environmental
Health Perspectives, 112(10), 1116-1124. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/15738787
36.	Davis MA, HigginsJ, Li Z, Gilbert-Diamond D, Baker ER, Das A and Karagas MR. (2015). Preliminary analysis of in utero
low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports.
Environmental Health, 14(1), 12. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/75971349
37.	Concha G, Vogler G, Lezcano D, Nermell B and Vahter M. (1998). Exposure to inorganic arsenic metabolites during
early human development. Toxicological Sciences, 44(2), 185-190. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/9742656
38.	Gilbert-Diamond D, EmondJA, Baker ER, Korrick SA and Karagas MR. (2016). Relation between in utero arsenic exposure
and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environmental Health Perspectives,
124(8), 1299. Retrieved from https://ehp.niehs.nih.gOV/15-10065/
39.	Harley KG, ChevrierJ, Schall RA, Sjodin A, Bradman A and Eskenazi B. (2011). Association of prenatal exposure to
polybrominated diphenyl ethers and infant birth weight. American Journal of Epidemiology, 174(8), 885-892. Retrieved from
https://www.ncbi.nlm.nih.gov/pijbmed/71878473
40.	Center for Children's Health the Environment Microbiome and Metabolomics' Center, Stakeholders documentary. 2016.
https://www.youtube.com/watch7vHKsOZB7dAmw
41.	American Cancer Society. (2016). Cancers that develop in children. Retrieved from http://www.cancer.org/cancer/
cancerinchildren/detailedguide/cancer-in-children-types-of-childhood-cancers
42.	American Cancer Society. (2016). Key statistics for childhood cancers. Retrieved from https://www.cancer.org/cancer/
cancer-in-children/kev-statistics. html
43.	Giddings BM, Whitehead TP, Metayer C and Miller MD. (2016). Childhood leukemia incidence in California: high and rising in
the Hispanic population. Cancer, 122(18), 2867-2875. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27351365
44.	Barrington-TrimisJL, Cockburn M, Metayer C, Gauderman WJ, WiemelsJ and McKean-Cowdin R. (2015). Rising rates of acute
lymphoblastic leukemia in Hispanic children: trends in incidence from 1992 to 2011. Blood, 125(19), 3033-3034. Retrieved
from http://www.bloodjournal.org/content/125/19/3033?sso-checked=true
45.	US Environmental Protection Agency. (2015). Center for Integrative Research on Childhood Leukemia and the Environment
(CIRCLE): Final progress report. Retrieved from https://cfpijb.epa.gov/ncer abstracts/index.cfm/fuseaction/displav.
high light/abstract/9219/report/F
46.	National Cancer Institute. (2016). Childhood cancers. Retrieved from https://www.cancer.gov/types/childhood-cancers
47.	Whitehead TP, Metayer C, WiemelsJL, Singer AW and Miller MD. (2016). Childhood leukemia and primary prevention. Current
Problems in Pediatric and Adolescent Health Care, 46(10), 317-352. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC5161115/
48.	Gunier RB, Kang A, Hammond SK, Reinier K, Lea CS, ChangJS, Does M, et al. (2017). A task-based assessment of parental
occupational exposure to pesticides and childhood acute lymphoblastic leukemia. Environmental Research, 156, 57-62.
Retrieved from http://www.sciencedirect.com/science/article/pii/S0013935116311860
83
-------
REFERENCES
HEALTH OUTCOMES
49.	Metayer C, Scelo G, Kang AY, Gunier RB, Reinier K, Lea S, ChangJS, et al. (2016). A task-based assessment of
parental occupational exposure to organic solvents and other compounds and the risk of childhood leukemia in
California. Environmental Research, 151,174-183. Retrieved from http://www.sciencedirect.com/science/article/pii/
5001393.5116307871
50.	Metayer C, Milne E, DockertyJ, ClavelJ, Pombo-de-Oliveira M, Wesseling C, Spector L, et al. (2014). Maternal
supplementation with folic acid and other vitamins before and during pregnancy and risk of leukemia in the offspring: a
Childhood Leukemia International Consortium (CLIC) study. Epidemiology, 25(6), 811-822. Retrieved from https://www.ncbi.
nlm.nih.gov/pubmed/75707954
51.	Deziel N, Rull R, Colt J, Reynolds P, Whitehead T, Gunier R, Month S, et al. (2014). Polycyclic aromatic hydrocarbons in
residential dust and risk of childhood acute lymphoblastic leukemia. Environmental Research, 133, 388-395. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/24948546
52.	Ward MH, Colt JS, Deziel NC, Whitehead TP, Reynolds P, Gunier RB, Nishioka M, et al. (2014). Residential levels of
polybrominated diphenyl ethers and risk of childhood acute lymphoblastic leukemia in California. Environmental Health
Perspectives, 122(10), 1110-1116. Retrieved from https://ehp.niehs.nih.gov/1307602/
53.	Ward MH, Colt JS, Metayer C, Gunier RB, Lubin J, Crouse V, Nishioka MG, et al. (2009). Residential exposure to
polychlorinated biphenyls and organochlorine pesticides and risk of childhood leukemia. Environmental Health
Perspectives, 117(6), 1007-13. Retrieved from https://ehp.niehs.nih.gov/0900583/
54.	Whitehead T, Brown F, Metayer C, ParkJ-S, Does M, Petreas M, Buffler P, et al. (2013). Polybrominated diphenyl ethers in
residential dust: sources of variability. Environment International, 57-58,11-24. Retrieved from https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC3668857/
55.	Whitehead TP, Brown FR, Metayer C, ParkJ-S, Does M, DhaliwalJ, Petreas MX, et al. (2014). Polychlorinated biphenyls in
residential dust: sources of variability. Environmental Science & Technology, 48(1), 157-164. Retrieved from https://www.
ncbi.nlm.nih.gov/pubmed/24313682
56.	Whitehead TP, Metayer C, Petreas M, Does M, Buffler PA and Rappaport SM. (2013). Polycyclic aromatic hydrocarbons in
residential dust: sources of variability. Environmental Health Perspectives, 121(5), 543-550. Retrieved from https://ehp.
niehs.nih.gov/1205821/
57.	Whitehead T, Crispo S, S, ParkJ, Petreas M, Rappaport SW and Metayer C. (2015). Concentrations of persistent organic
pollutants in California children's whole blood and residential dust. Environmental Science &Technology, 49(15), 9331-9340.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26147951
58.	Whitehead TP, Smith SC, ParkJ-S, Petreas MX, Rappaport SM and Metayer C. (2015). Concentrations of persistent organic
pollutants in California women's serum and residential dust. Environmental research, 136, 57-66. Retrieved from https://
www.ncbi.nlm.nih.gov/pijbmed/75460671
59.	WiemelsJ. (2012). Perspectives on the causes of childhood leukemia. Chemico-biological Interactions, 196(3), 59-67.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839796/
60.	Noriega DB and Savelkoul HF. (2014). Immune dysregulation in autism spectrum disorder. European Journal of Pediatrics,
173(1), 33-43. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/74797668
61.	GreggJ, Lit L, Baron C, Hertz-Picciotto I, Walker W, Davis R, Croen L, et al. (2008). Gene expression changes in children with
autism. Genomics, 91(1), 22-29. Retireved from https://www.ncbi.nlm.nih.gov/pubmed/18006270
62.	Thomsen SF. (2015). Epidemiology and natural history of atopic diseases. European Clinical Respiratoryjournal, 2(1), 1-6.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629767/
63.	National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2016). Handout on health: Atopic dermatitis (a type of
eczema). Retrieved from https://www.niams.nih.gov/health info/Atopic Dermatitis/default.asp
84
-------
REFERENCES
HEALTH OUTCOMES
64.	Ashwood P, SchauerJ, Pessah I and Van d, Water, J. (2009). Preliminary evidence of the in vitro effects of BDE-47 on innate
immune responses in children with autism spectrum disorders. Journal of Neuroimmunology, 208(1-2), 130-135. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692510/
65.	Krakowiak P, Goines PE, Tancredi DJ, Ashwood P, Hansen RL, Hertz-Picciotto I and Van de Water J. (2017). Neonatal cytokine
profiles associated with autism spectrum disorder. Biological Psychiatry, 81(5), 442-451. Retrieved from https://www.nchi.
nlm.nih.gov/pubmed/26392128
66.	Akintunde ME, Rose M, Krakowiak P, Heuer L, Ashwood P, Hansen R, Hertz-Picciotto I, et al. (2015). Increased production
of IL-17 in children with autism spectrum disordersand co-morbid asthma. Journal of Neuroimmunology, 286, 33-41.
Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/76798377
67.	Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen L, Ozonoff S, et al. (2008). Decreased transforming
growth factor betal in autism: a potential link between immune dysregulation and impairment in clinical behavioral
outcomes. Journal of Neuroimmunology, 204(1-2), 149-153. Retrieved from http://www.sciencedirect.com/science/article/
pii/SOl 65577808007937
68.	Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I and Van d, Water,J. (2011). Elevated plasma cytokines
in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral
outcome. Brain, Behavior, and Immunity, 25(1), 40-45. Retrieved from http://www.sciencedirect.com/science/article/pii/
S0889159110004789
69.	Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I and Van d, Water, J. (2011). Associations of impaired behaviors
with elevated plasma chemokines in autism spectrum disorders. Journal of Neuroimmunology, 232(1-2), 196-199. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053074/
70.	ChangJS, Tsai C-R, Tsai Y-W and WiemelsJL. (2012). Medically diagnosed infections and risk of childhood leukaemia: a
population-based case-control study. Internationaljournal of Epidemiology, 41(4), 1050-1059. Retrieved from https://www.
ncbi.nlm.nih.gov/labs/articles/22836110/
71.	ChangJS, Zhou M, Buffler PA, Chokkalingam AP, Metayer C and WiemelsJL. (2011). Profound deficit of IL10 at birth in children
who develop childhood acute lymphoblastic leukemia. Cancer Epidemiology and Prevention Biomarkers, 20(8), 1736-1740.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257311/pdf/nihms301956.pdf
72.	Braunschweig D, Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen L, Pessah I, et al. (2008). Autism: Maternally
derived antibodies specific for fetal brain proteins. Neurotoxicology, 29(2), 226-231. Retrieved from https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC2305723/
73.	Braunschweig D, Krakowiak P, Duncanson P, Boyce R, Hansen R, Ashwood P, Hertz-Picciotto I, et al. (2013). Autism-specific
maternal autoantibodies recognize critical proteins in developing brain. Translational Psychiatry, 3(7), e277. Retrieved from
http://www.natijre.com/tp/joijrnal/v3/n7/fijll/tp701350a.html
74.	Krakowiak P, Walker CK, Tancredi D, HertzDPicciotto I and Van de Water J. (2017). AutismElspecific maternal antiDfetal brain
autoantibodies are associated with metabolic conditions. Autism Research, 10(1), 89-98. Retrieved from https://www.ncbi.
nlm.nih.gov/pubmed/27312731
75.	Hew K, Walker A, Kohli A, Garcia M, Syed A, McDonaldEIHyman C, Noth E, et al. (2015). Childhood exposure to ambient
polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clinical &
Experimental Allergy, 45(1), 238-248. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396982/
76.	Grandjean P and Landrigan PJ. (2006). Developmental neurotoxicity of industrial chemicals. The Lancet, 368(9553), 2167-
2178. Retrieved from http://www.thelancet.com/journals/laneur/article/PII.S1474-4477f13l70778-3/abstract
77.	Perera F, Rauh V, Whyatt R, Tsai W-Y, Tang D, Diaz D, Hoepner L, et al. (2006). Effect of prenatal exposure to airborne
polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environmental
Health Perspectives, 114(8), 1287-1292. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551985/
85
-------
REFERENCES
HEALTH OUTCOMES
78.	Perera F, Li Z, Whyatt R, Hoepner L, Wang S, Camann D and Rauh V. (2009). Prenatal airborne polycyclic aromatic
hydrocarbon exposure and child IQ at age 5 years. Pediatrics, 124(2), e195-e202. Retrieved from https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC2864932/
79.	Perera F, Tang D, Wang S, VishnevetskyJ, Zhang B, Diaz D, Camann D, et al. (2012). Prenatal polycyclic aromatic hydrocarbon
(PAH) exposure and child behavior at age 6-7 years. Environmental Health Perspectives, 120(6), 921-926. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385432/
80.	Peterson BS, Rauh VA, Bansal R, HaoX, Toth Z, Nati G, Walsh K, et al. (2015). Effects of prenatal exposure to air pollutants
(polycyclic aromatic hydrocarbons) on the development of brain white matter, cognition, and behavior in later childhood.
JAMA Psychiatry, 72(6), 531-540. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/75807066
81.	Perera F, Chang H, Tang D, Roen E, HerbstmanJ, Margolis A, Huang T, et al. (2014). Early-life exposure to polycyclic aromatic
hydrocarbons and ADHD behavior problems. PLoS One, 9(11), e111670. Retrieved from http://journals.plos.org/plosone/
article?id=10.1371/journal, pone.0111670
82.	Margolis AE, HerbstmanJB, Davis KS, Thomas VK, Tang D, Wang Y, Wang S, et al. (2016). Longitudinal effects of prenatal
exposure to air pollutants on selfdregulatory capacities and social competence. Journal of Child Psychology and Psychiatry,
57(7), 851 -860. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/jcpp.12548/abstract
83.	Lovasi G, Quinn J, Rauh V, Perera F, Andrews H, Garfinkel R, Hoepner L, et al. (2011). Chlorpyrifos exposure and urban
residential environment characteristics as determinants of early childhood neurodevelopment. American Journal of Public
Health, 101(1), 63-70. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000714/
84.	Whyatt RM, Camann DE, Kinney PL, Reyes A, Ramirez J, Dietrich J, Diaz D, et al. (2002). Residential pesticide use during
pregnancy among a cohort of urban minority women. Environmental Health Perspectives, 110(5), 507-514. Retrieved from
https://www.ncbi.nlm.nih.gov/pijbmed/17003754
85.	Rauh V, Garfinkel R, Perera F, Andrews H, Hoepner L, Barr D, Whitehead R, et al. (2006). Impact of prenatal chlorpyrifos
exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics, 118(6), e1845-e1859.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390915/
86.	Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB and Whyatt R. (2011). Seven-year neurodevelopmental scores
and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environmental Health Perspectives, 119(8), 1196-
1201. Retrieved from https://ehp.niehs.nih.gov/1003160/
87.	Horton MK, Kahn LG, Perera F, Barr DB and Rauh V. (2012). Does the home environment and the sex of the child modify the
adverse effects of prenatal exposure to chlorpyrifos on child working memory? Neurotoxicology and Teratology, 34(5), 534-
541. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901426/
88.	Rauh VA, Perera FP, Horton MK, Whyatt RM, Bansal R, HaoX, Liu J, et al. (2012). Brain anomalies in children exposed
prenatally to a common organophosphate pesticide. Proceedings of the National Academy of Sciences, 109(20), 7871-7876.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356641/
89.	US Environmental Protection Agency. America's children and the environment: Neurodevelopmental disorders. 2015;
Available from: https://www.epa.gov/sites/production/files/2015-10/documents/ace3 neurodevelopmental.pdf
90.	US Environmental Protection Agency. (2015). Benefit and cost analysis for the effluent limitations guidelines and standards
for the stream electric power generating point source category. Retrieved from https://www.epa.gov/sites/prodiJction/
files/2015-10/documents/steam-electric benefit-cost-analvsis 09-29-2015.pdf
91.	Casey B, Jones RM and HareTA. (2008). The adolescent brain. Annals of the New York Academy of Sciences, 1124(1), 111-126.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475802/
92.	Philippat C, Bennett DH, Krakowiak P, Rose M, Hwang H-M and Hertz-Picciotto I. (2015). Phthalate concentrations in house
dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics and
the Environment (CHARGE) study. Environmental Health, 14(1), 56-66. Retrieved from https://ehjournal.biomedcentral.com/
articles/10.1186/s17940-015-0074-9
86
-------
REFERENCES
HEALTH OUTCOMES
93.	Centers for Disease Control and Prevention. Autism and development disabilities monitoring network. 2009; Available from:
https://www.cdc.gov/ncbddd/autism/states/addmcommunityreport2009.pdf
94.	Rosenberg RE, LawJK, Yenokyan G, McGreadyJ, Kaufmann WE and Law PA. (2009). Characteristics and concordance
of autism spectrum disorders among 277 twin pairs. Archives of Pediatrics and Adolescent Medicine, 163(10), 907-914.
Retrieved from http://jamanetwork.com/joijrnals/jamapediatrics/fijllarticle/387775
95.	HallmayerJ, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, et al. (2011). Genetic heritability and shared
environmental factors among twin pairs with autism. Archives of General Psychiatry, 68(11), 1095-1102. Retrieved from
http://jamanetwork.com/journals/jamapsychiatry/fullarticle/1107328
96.	Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM and Reichenberg A. (2014). The familial risk of autism.
JAMA, 311(17), 1770-1777. Retrieved from http://jamanetwork.com/joijrnals/jama/fijllarticle/1866100
97.	Centers for Disease Control and Prevention. Autism data and statistics. 2017; Available from: https://www.cdc.gov/ncbddd/
autism/data, html
98.	Christensen DL, BaioJ, Braun KV, Bilder D, CharlesJ and al. e. (2016). Prevalence and characteristics of autism spectrum
disorder among children aged 8 years — Autism and developmental disabilities monitoring network, 11 sites, United States.
MMWR Surveill Summ, 65(No.SS-3), 1-23. Retrieved from https://www.cdc.gov/mmwr/volumes/65/ss/ss6503a1.htm
99.	Lavelle TA, Weinstein MC, NewhouseJP, Munir K, Kuhlthau KA and Prosser LA. (2014). Economic burden of childhood
autism spectrum disorders. Pediatrics, 133(3), e520-e529. Retrieved from http://pediatrics.aappublications.org/content/
earlv/7014/07/04/peds. 7013-0763
100.	Volk H, Hertz-Picciotto I, Delwiche L, Lurmann Fand McConnell R. (2011). Residential proximity to freeways and autism in
the CHARGE Study. Environmental Health Perspectives, 119(6), 873-877. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3114875/
101.	Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I and McConnell R. (2013). Traffic-related air pollution, particulate matter, and
autism. JAMA Psychiatry, 70(1), 71-77. Retrieved from http://jamanetwork.com/journals/jamapsychiatry/fullarticle/1393589
102.	McCanlies EC, Fekedulegn D, Mnatsakanova A, Burchfiel CM, Sanderson WT, Charles LE and Hertz-Picciotto I. (2012).
Parental occupational exposures and autism spectrum disorder. Journal of Autism and Developmental Disorders, 42(11),
2323-2334. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/77399411
103.	SheltonJF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, Hansen RL, et al. (2014). Neurodevelopmental
disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environmental Health
Perspectives, 122(10), 1103-1109. Retrieved from https://ehp.niehs.nih.gov/1307044/
104.	Volk HE, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R and Campbell DB. (2014). Autism spectrum disorder: interaction
of air pollution with the MET receptor tyrosine kinase gene. Epidemiology 25(1), 44-47. Retrieved from https://www.ncbi.
nlm.nih.gov/pubmed/24240654
105.	Grun Fand Blumberg B. (2009). Minireview: the case for obesogens. Molecular Endocrinology, 23(8), 1127-1134. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718750/
106.	Grun F. (2010). Obesogens. Current Opinion in Endocrinology, Diabetes and Obesity, 17(5), 453-459. Retrieved from https://
www.ncbi.nlm.nih.gov/pubmed/20689419
107.	FraylingTM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, PerryJR, et al. (2007). A common variant in the
FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316(5826), 889-894.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17434869
108.	Gillman MW and Ludwig DS. (2013). How early should obesity prevention start? New England Journal of Medicine, 369(23),
2173-2175. Retrieved from http://www.nejm.Org/doi/full/10.1056/NEIMp1310577#t=article
87
-------
REFERENCES
HEALTH OUTCOMES
109.	Lukaszewski M-A, Mayeur S, Fajardy I, Delahaye F, Dutriez-Casteloot I, Montel V, Dickes-Coopman A, et al. (2011). Maternal
prenatal undernutrition programs adipose tissue gene expression in adult male rat offspring under high-fat diet. American
Journal of Physiology-Endocrinology and Metabolism, 301(3), E548-E559. Retrieved from http://ajpendo.physiology.org/
content/earlv/7011/06/73/ajpendo.00011.7011
110.	Sebert S, Sharkey D, Budge H and Symonds ME. (2011). The early programming of metabolic health: is epigenetic setting the
missing link? The American Journal of Clinical Nutrition, 94(6 Suppl), 1953S-1958S. Retrieved from https://www.ncbi.nlm.nih.
gov/pubmed/21543542
111.	Centers for Disease Control and Prevention. Childhood obesity facts. 2015: Available from: https://www.cdc.gov/
healthyschools/obesity/facts.htm
112.	Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK and Flegal KM. (2016). Trends in obesity prevalence
among children and adolescents in the United States, 1988-1994 through 2013-2014. JAMA, 315(21), 2292-2299. Retrieved
from http://jamanetwork.com/joijrnals/jama/fijllarticle/7576638
113.	Watkins DJ, Peterson KE, Ferguson KK, Mercado-Garcia A, Tamayoy Ortiz M, Cantoral A, MeekerJD, et al. (2016). Relating
phthalate and BPA exposure to metabolism in peripubescence: the role of exposure timing, sex, and puberty. The Journal
of Clinical Endocrinology, 101(1), 79-88. Retrieved from https://academic.oup.eom/jcem/article/101/1/79/2806581 /Relating-
Phthalate-and-BPA-Fxposure-to-Metabolism
114.	Perng W, Watkins DJ, Cantoral A, Mercado-Garcia A, MeekerJD, Tellez-Rojo MM and Peterson KE. (2017). Exposure to
phthalates is associated with lipid profile in peripubertal Mexican youth. Environmental Research, 154, 311-317. Retrieved
from http://www.sciencedirect.com/science/article/pii/S0013935116310313
115.	Lu KD, Breysse PN, Diette GB, Curtin-Brosnan J, Aloe C, D'ann LW, Peng RD, et al. (2013). Being overweight increases
susceptibility to indoor pollutants among urban children with asthma. Journal of Allergy and Clinical Immunology, 131(4),
1017-1023. e3. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23403052
116.	Jerrett M, McConnell R, Wolch J, Chang R, Lam C, Dunton G, Gilliland F, et al. (2014). Traffic-related air pollution and obesity
formation in children: a longitudinal, multilevel analysis. Environmental Health, 13(1), 49-58. Retrieved from https://
ehjoijrnal.biomedcentral.com/articles/10.1186/1476-069X-13-49
117.	McConnell R, Shen E, Gilliland FD, Jerrett M, Wolch J, Chang C-C, Lurmann F, et al. (2015). A longitudinal cohort study of
body mass index and childhood exposure to secondhand tobacco smoke and air pollution: the Southern California
Children's Health Study. Environmental Health Perspectives, 123(4), 360-366. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/75389775
118.	Rundle A, Hoepner L, Hassoun A, Oberfield S, Freyer G, Holmes D, Reyes M, et al. (2012). Association of childhood
obesity with maternal exposure to ambient air polycyclic aromatic hydrocarbons during pregnancy. American Journal of
Epidemiology, 175(11), 1163-1172. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491973/
119.	Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, Diaz D, et al. (2016). Bisphenol A and adiposity in
an inner-city birth cohort. Environmental Health Perspectives, 124(10), 1644-1650. Retrieved from https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC5047776/
120.	GutschowW, USC Environmental Health Centers to host parks, pollution and obesity convening. 7017. http://
envhealthcenters. usc.edi j/7017/07/usc-environmental-health-centers-to-host-parks-pollution-and-obesity-convening-
april-17-2017.html
121.	Traggiai C and Stanhope R. (2003). Disorders of pubertal development. Best Practice & Research Clinical Obstetrics &
Gynaecology, 17(1), 41-56. Retrieved from http://www.ncbi.nlm.nih.gov/pijbmed/17758775
122.	Watkins DJ, Tellez-Rojo MM, Ferguson KK, LeeJM, Solano-Gonzalez M, Blank-Goldenberg C, Peterson KE, et al. (2014). In
utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. Environmental Research,
134, 233-241. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25173057
88
-------
REFERENCES
HEALTH OUTCOMES
123.	Watkins DJ, Sanchez BN, Tellez-Rojo MM, LeeJM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, et al. (2017).
Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and
pubertal development in girls. Environmental Research, 159,143-151. Retrieved from http://www.sciencedirect.com/
science/article/pii/S0013935117309106
124.	Ferguson KK, Peterson KE, LeeJM, Mercado-Garcia A, Blank-Goldenberg C, Tellez-Rojo MM and MeekerJD. (2014). Prenatal
and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys. Reproductive Toxicology, 47,
70-76. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24945889
125.	Watkins DJ, Sanchez BN, Tellez-Rojo MM, LeeJM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, et al. (2017).
Impact of phthalate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual
maturation in peripubertal males. Environmental Health, 16(1), 69. Retrieved from https://ehjournal.biomedcentral.com/
articles/10.1186/s17940-017-0778-5
126.	Wolff M, Teitelbaum S, McGovern K, Windham G, Pinney S, Galvez M, Calafat A, et al. (2014). Phthalate exposure and
pubertal development in a longitudinal study of US girls. Human Reproduction, 29(7), 1558-1566. Retrieved from https://
www.ncbi.nlm.nih.gov/pubmed/24781428
127.	Harley KG, Rauch SA, ChevrierJ, Kogut K, Parra KL, Trujillo C, Lustig RH, et al. (2017). Association of prenatal and childhood
PBDE exposure with timing of puberty in boys and girls. Environment International, 100,132-138. Retrieved from https://
www.ncbi.nlm.nih.gov/labs/articles/28089583/
89
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
1.	Dockery D, Outdoor Air Pollution, in Textbook of Children's Environmental Health, P. Ladnrigan and R. Etzel, Editors. 2014,
Oxford University Press: New York, NY. p. 201-209.
2.	American Academy of Pediatrics Committee on Environmental Health. (2004). Ambient air pollution: health hazards to
children. Pediatrics, 114(6), 1699-1707. Retrieved from http://pediatrics.aappublications.Org/content/114/6/1699.abstract
3.	US Environmental Protection Agency. Overview of the Clean Air Act and air pollution. 2017; Available from: https://www.epa.
gov/clean-air-act-overview
4.	Gauderman W, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, McConnell R, et al. (2004). The effect of air pollution on lung
development from 10 to 18 years of age. New England Journal of Medicine, 351(11), 1057-1067. Retrieved from http://www.
nejm.org/doi/full/10.1056/nejmoa040610
5.	Gauderman W, Vora H, McConnell R, Berhane K, Gilliland F, Thomas D, Lurmann F, et al. (2007). Effect of exposure to traffic
on lung development from 10 to 18 years of age: a cohort study. Lancet, 369(9561), 571-577. Retrieved from https://www.
ncbi.nlm.nih.gov/pubmed/17307103
6.	Gauderman W, McConnell R, Gilliland F, London S, Thomas D, Avol E, Vora H, et al. (2000). Association between air pollution
and lung function growth in southern California children. American Journal of Respiratory and Critical Care Medicine, 162(4
Pt 1), 1383-1390. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11029349
7.	US Environmental Protection Agency. (2013). Integrated Science Assessment for ozone and related photochemical oxidants.
Retrieved from https://www.epa.gov/isa/integrated-science-assessment-isa-ozone
8.	US Environmental Protection Agency. (2009). Integrated Science Assessment for particulate matter. Retrieved from https://
cfpub.epa.gov/ncea/risk/recordisplay.cfm?deid=716546
9.	US Environmental Protection Agency. (2016). Integrated Science Assessment for nitrogen dioxide- health criteria. Retrieved
from https://www.epa.gov/isa/integrated-science-assessment-isa-nitrogen-dioxide-health-criteria
10.	Vasquez V, Minkler M and Shepard P. (2006). Promoting environmental health policy through community based
participatory research: a case study from Harlem, New York. Journal of Urban Health, 83(1), 101-110. Retrieved from https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC2258322/
11.	California Legislature, SB-352 Schoolsites: Sources of pollution, in Senate Bill No. 352. 2003. http://leginfo.legislature.ca.gov/
faces/billNavClient.xhtml?bill id=200320040SB352
12.	Barboza T, L.A. City Council adopts rules to ease health hazards in polluted neighborhoods, in Los Angeles Times. 2016.
http://www.latimes.com/local/lanow/la-me-polkjtion-protection-70160417-story.html
13.	Padula A, Mortimer K, Tager I, Hammond S, Lurmann F, Yang W, Stevenson D, et al. (2014). Traffic-related air pollution and
risk of preterm birth in the San Joaquin Valley of California. Annals of Epidemiology, 24(12), 888-895.e4. Retrieved from
http://www.sciencedirect.com/science/article/pii/S1047279714004463
14.	Padula AM, Yang W, Carmichael SL, Lurmann F, BalmesJ, Hammond SK and Shaw GM. (2017). Air pollution, neighborhood
acculturation factors, and neural tube defects among Hispanic women in California. Birth Defects Research, 109(6), 403-
422. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/bdra.236Q2/full
15.	Padula AM, Yang W, Carmichael SL, Tager IB, Lurmann F, Hammond SK and Shaw GM. (2015). Air pollution, neighbourhood
socioeconomic factors, and neural tube defects in the Sanjoaquin Valley of California. Paediatric and Perinatal
Epidemiology, 29(6), 536-545. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26443985
16.	Cossi M, Zuta S, Padula AM, Gould JB, Stevenson DK and Shaw GM. (2015). Role of infant sex in the association between air
pollution and preterm birth. Annals of Epidemiology, 25(11), 874-876. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4671488/
17.
90
Padula AM, Noth EM, Hammond SK, Lurmann FW, Yang W, Tager IB and Shaw GM. (2014). Exposure to airborne polycyclic
aromatic hydrocarbons during pregnancy and risk of preterm birth. Environmental Research, 135, 221-226. Retrieved from
https://www.ncbi.nlm.nih.gov/piJbmed/75787780
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
18.	Berhane K, Chang C-C, McConnell R, Gauderman WJ, Avol E, Rapapport E, Urman R, et al. (2016). Association of changes
in air quality with bronchitic symptoms in children in California, 1993-2012. Journal of the American Medical Association,
315(14), 1491-1501. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27115265
19.	Gauderman WJ, Urman R, Avol E, Berhane K, McConnell R, Rappaport E, Chang R, et al. (2015). Association of improved air
quality with lung development in children. New England Journal of Medicine, 372(10), 905-913. Retrieved from http://www.
nejm.org/doi/full/10.1056/NEIMoa1414123#t=article
20.	Eggleston P, Butz A, Rand C, Curtin-Brosnan J, Kanchanaraksa S, Swartz L, Breysse P, et al. (2005). Home environmental
intervention in inner-city asthma: a randomized controlled clinical trial. Annals of Allergy Asthma & Immunology, 95(6), 518-
524. Retrieved from http://www.sciencedirect.eom/science/article/pii/.S1081170610610175
21.	Butz A, Matsui E, Breysse P, Curtin-Brosnan J, Eggleston P, Diette G, Williams D, et al. (2011). A randomized trial of air
cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke
exposure. Archives of Pediatrics and Adolescent Medicine, 165(8), 741-748. Retrieved from https://www.ncbi.nlm.nih.gov/
pnhmed/71810636
22.	Perera F, Rauh V, Whyatt R, Tsai W-Y, Tang D, Diaz D, Hoepner L, et al. (2006). Effect of prenatal exposure to airborne
polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environmental
Health Perspectives, 114(8), 1287-1292. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551985/
23.	Perera F, Li Z, Whyatt R, Hoepner L, Wang S, Camann D and Rauh V. (2009). Prenatal airborne polycyclic aromatic
hydrocarbon exposure and child IQ at age 5 years. Pediatrics, 124(2), e195-e202. Retrieved from https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC2864932/
24.	Perera F, Tang D, Wang S, VishnevetskyJ, Zhang B, Diaz D, Camann D, et al. (2012). Prenatal polycyclic aromatic hydrocarbon
(PAH) exposure and child behavior at age 6-7 years. Environmental Health Perspectives, 120(6), 921-926. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385432/
25.	Perera F, Chang H, Tang D, Roen E, HerbstmanJ, Margolis A, Huang T, et al. (2014). Early-life exposure to polycyclic aromatic
hydrocarbons and ADHD behavior problems. PLoS One, 9(11), e111670. Retrieved from http://joijrnals.plos.org/plosone/
article?id=10.1371/journal, pone.0111670
26.	Margolis AE, HerbstmanJB, Davis KS, Thomas VK, Tang D, Wang Y, Wang S, et al. (2016). Longitudinal effects of prenatal
exposure to air pollutants on self-regulatory capacities and social competence. Journal of Child Psychology and Psychiatry,
57(7), 851 -860. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/jcpp.17548/abstract
27.	VishnevetskyJ, Tang D, Chang H, Roen E, Wang Y, Rauh V, Wang S, et al. (2015). Combined effects of prenatal polycyclic
aromatic hydrocarbons and material hardship on child IQ. Neurotoxicology and Teratology, 49, 74-80. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/25912623
28.	Perera F, Weiland K, Neidell M and Wang S. (2014). Prenatal exposure to airborne polycyclic aromatic hydrocarbons and IQ:
Estimated benefit of pollution reduction. Journal of Public Health Policy, 35(3), 327-336. Retrieved from https://www.ncbi.
nlm.nih.gov/pubmed/24804951
29.	Gale S, Noth E, Mann J, BalmesJ, Hammond S and Tager I. (2012). Polycyclic aromatic hydrocarbon exposure and wheeze in
a cohort of children with asthma in Fresno, CA. Journal of Exposure Science and Environmental Epidemiology, 22(4), 386-
392. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719417/
30.	Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, BalmesJ and Tager I. (2010). Ambient air pollution impairs
regulatory T-cell function in asthma. Journal of Allergy and Clinical Immunology, 126(4), 845-852. e10. Retrieved from
https://www.ncbi.nlm.nih.gov/piJbmed/70970773
31.	Hew K, Walker A, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth E, et al. (2015). Childhood exposure to ambient
polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clinical
and Experimental Allergy, 45(1), 238-248. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396982/
91
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
32.	Noth EM, Hammond SK, Biging GS and Tager IB. (2011). A spatial-temporal regression model to predict daily outdoor
residential PAH concentrations in an epidemiologic study in Fresno, CA. Atmospheric Environment, 45(14), 2394-2403.
Retrieved from http://www.sciencedirect.com/science/article/pii/S1352231011001385
33.	Patel M, Hoepner L, Garfinkel R, Chillrud S, Reyes A, QuinnJ, Perera F, et al. (2009). Ambient metals, elemental carbon, and
wheeze and cough in New York City children through 24 months of age. American Journal of Respiratory and Critical Care
Medicine, 180(11), 1107-1113. Retrieved from http://www.atsjournals.Org/doi/abs/10.1164/rccm.200901-0122QC
34.	Jackson B, Taylor V, Karagas M, Punshon T and Cottingham K. (2012). Arsenic, organic foods, and brown rice syrup.
Environmental Health Perspectives, 120(5), 623-626. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3346791/
35.	Agency for Toxic Substances and Disease Registry. (2016). Addendum to the toxicological profile for arsenic. https://www.
atsdr.cdc.gov/toxprofiles/Arsenic addendum.pdf
36.	Agency for Toxic Substances and Disease Registry. (2007). Toxicological profile for arsenic, https://www.atsdr.cdc.gov/
toxprofiles/tp7.pdf
37.	European Food Safety Authority. (2009). EFSA Panel on Contaminants in the Food Chain Scientific Opinion on Arsenic in
Food. European Food Safety Authorityjournal, 7(10), 1351. Retrieved from http://www.efsa.europa.eu/en/efsajournal/
pub/1351
38.	World Health Organization. Arsenic. 2016; Available from: http://www.who.int/mediacentre/factsheets/fs372/en/
39.	US Environmental Protection Agency. About private water wells. 2016; Available from: https://www.epa.gov/privatewells/
about-private-water-wells
40.	Davis MA, HigginsJ, Li Z, Gilbert-Diamond D, Baker ER, Das A and Karagas MR. (2015). Preliminary analysis of in utero
low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports.
Environmental Health, 14(1), 12. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479981/
41.	Gilbert-Diamond D, EmondJA, Baker ER, Korrick SA and Karagas MR. (2016). Relation between in utero arsenic exposure
and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environmental Health Perspectives,
124(8), 1299-1307. Retrieved from https://ehp.niehs.nih.gov/15-10065/
42.	Farzan SF, Chen Y, ReesJR, Zens MS and Karagas MR. (2015). Risk of death from cardiovascular disease associated with low-
level arsenic exposure among long-term smokers in a US population-based study. Toxicology and Applied Pharmacology,
287(2), 93-97. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26048586
43.	Farzan SF, Korrick S, Li Z, Enelow R, Gandolfi AJ, Madan J, Nadeau K, et al. (2013). In utero arsenic exposure and infant
infection in a United States cohort: a prospective study. Environmental Research, 126, 24-30. Retrieved from https://www.
ncbi.nlm.nih.gov/pijbmed/73769761
44.	Nadeau K, Li Z, Farzan S, Koestler D, Robbins D, Fei D, Malipatlolla M, et al. (2014). In utero arsenic exposure and
fetal immune repertoire in a US pregnancy cohort. Clinical Immunology, 155(2), 188-197. Retrieved from http://www.
sciencedirect.com/science/article/pii/S1571661614007150
45.	Koestler D, Avissar-Whiting M, Houseman E, Karagas M and Marsit C. (2013). Differential DNA methylation in umbilical cord
blood of infants exposed to low levels of arsenic in utero. Environmental Health Perspectives, 121(8), 971-977. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733676/
46.	Fei DL, Koestler DC, Li Z, Giambelli C, Sanchez-Mejias A, GosseJA, Marsit CJ, et al. (2013). Association between In Utero
arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study. Environmental Health, 12(1),
58. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23866971
47.	US Environmental Protection Agency. (2014). IRIS toxicological review of inorganic arsenic (preliminary assessment
materials). Retrieved from https://cfpijb.epa.gov/ncea/iris drafts/recordisplay.cfm?deid=309710
92
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
48.	US Food and Drug Administration. (2016). Inorganic arsenic in rice cereals for infants: action level guidance for industry -
Draft guidance. http://www.fda.gov/downloads/Food/GuidanceRegulation/GuidanceDocumentsRegulatorylnformation/
[JCM493157.pdf
49.	Rep. DeLauro RL, Reducing food-based Inorganic Compounds Exposure Act of 2015, in H.R. 2529, Congress, Editor. 2015.
https://www.congress.gov/hill/114th-congress/hoiJse-hill/7579
50.	Lai PY, Cottingham KL, Steinmaus C, Karagas MR and Miller MD. (2015). Arsenic and rice: translating research to address
health care providers' needs. The Journal of Pediatrics, 167(4), 797-803. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4779445/
51.	Dartmouth Children's Center. Arsenic tool. 2015; Available from: http://www.dartmoiJth.edij/~childrenshealth/arsenic/
52.	US Environmental Protection Agency. Bisphenal A action plan. 2010; Available from: https://www.epa.gov/assessing-and-
managing-chemicals-under-tsca/bisphenol-bpa-action-plan
53.	UC Berkeley Center for Environmental Research and Children's Health. Environmental exposures. 2017; Available from:
http://cerch.berkeley.edu/resources/environmental-exposures
54.	Kundakovic M, Gudsnuk K, Franks B, MadridJ, Miller R, Perera F and Champagne F. (2013). Sex-specific epigenetic disruption
and behavioral changes following low-dose in utero bisphenol A exposure. Proceedings of the National Academy of
Sciences USA, 110(24), 9956-9961. Retrieved from http://www.pnas.org/content/110/24/9956.short
55.	Wise LM, Sadowski RN, Kim T, Willing J and JuraskaJM. (2016). Long-term effects of adolescent exposure to bisphenol Aon
neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type. Neurotoxicology, 53,186-
192. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808356/
56.	Ziv-Gal A, Wang W, Zhou C and Flaws JA. (2015). The effects of in utero bisphenol A exposure on reproductive capacity in
several generations of mice. Toxicology and Applied Pharmacology, 284(3), 354-362. Retrieved from https://www.ncbi.nlm.
nih.gov/pubmed/75771130
57.	US Environmental Protection Agency. Risk management for bisphenol A (BPA) 2017; Available from: https://www.epa.gov/
assessing-and-managing-chemicals-under-tsca/risk-management-bisphenol-bpa
58.	Gao H, Yang B-J, Li N, Feng L-M, Shi X-Y, Zhao W-H and Liu S-J. (2015). Bisphenol A and hormone-associated cancers: current
progress and perspectives. Medicine, 94(1), e211. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602822/
59.	Braun JM, Lanphear BP, Calafat AM, Deria S, KhouryJ, Howe CJ and Venners SA. (2014). Early-life bisphenol A exposure and
child body mass index: a prospective cohort study. Environmental Health Perspectives, 122(11), 1239-1245. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/25073184
60.	Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, Diaz D, et al. (2016). Bisphenol A and adiposity in
an inner-city birth cohort. Environmental Health Perspectives, 124(10), 1644-1650. Retrieved from https://www.ncbi.nlm.
nih.gov/pubmed/27187982
61.	Harley KG, Schall RA, ChevrierJ, Tyler K, Aguirre H, Bradman A, Holland NT, et al. (2013). Prenatal and postnatal bisphenol A
exposure and body mass index in childhood in the CHAMACOS cohort. Environmental Health Perspectives, 121(4), 514-520.
Retrieved from https://ehp.niehs.nih.gov/1705548/
62.	Volberg V, Harley K, Calafat AM, Dave V, McFaddenJ, Eskenazi B and Holland N. (2013). Maternal bisphenol A exposure
during pregnancy and its association with adipokines in Mexican-American children. Environmental and Molecular
Mutagenesis, 54(8), 621-628. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23908009
63.	Yang TC, Peterson KE, Meeker JD, Sanchez BN, Zhang Z, Cantoral A, Solano M, et al. (2017). Bisphenol A and phthalates in
utero and in childhood: association with child BMI z-score and adiposity. Environmental Research, 156, 326-333. Retrieved
from https://www.ncbi.nlm.nih.gov/pubmed/28390300
93
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
64.	Perng W, Watkins DJ, Cantoral A, Mercado-Garcia A, MeekerJD, Tellez-Rojo MM and Peterson KE. (2017). Exposure to
phthalates is associated with lipid profile in peripubertal Mexican youth. Environmental Research, 154, 311-317. Retrieved
from http://www.sciencedirect.com/science/article/pii/S0013935116310313
65.	Watkins DJ, Peterson KE, Ferguson KK, Mercado-Garcia A, Tamayoy Ortiz M, Cantoral A, MeekerJD, et al. (2016). Relating
phthalate and BPA exposure to metabolism in peripubescence: the role of exposure timing, sex, and puberty. The Journal
of Clinical Endocrinology, 101(1), 79-88. Retrieved from https://academic.oup.eom/jcem/article/101/1/79/2806581 /Relating-
Phthalate-and-BPA-Exposure-to-Metabolism
66.	HerbstmanJ, Sjodin A, Kurzon M, Lederman S, Jones R, Rauh V, Needham L, et al. (2010). Prenatal exposure to PBDEs and
neurodevelopment. Environmental Health Perspectives, 118(5), 712-719. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/70056561
67.	Cowell WJ, Lederman SA, Sjodin A, Jones R, Wang S, Perera FP, Wang R, et al. (2015). Prenatal exposure to polybrominated
diphenyl ethers and child attention problems at 3-7years. Neurotoxicology and Teratology, 52(PtB), 143-150. Retrieved
from https://www.ncbi.nlm.nih.gov/pijbmed/76344673
68.	Chen A, Yolton K, Rauch SA, Webster GM, Hornung R, Sjodin A, Dietrich KN, et al. (2014). Prenatal polybrominated diphenyl
ether exposures and neurodevelopment in US children through 5 years of age: the HOME study. Environmental Health
Perspectives, 122(8), 856-862. Retrieved from https://ehp.niehs.nih.gov/1307567/
69.	Vuong AM, Yolton K, Webster GM, Sjodin A, Calafat AM, BraunJM, Dietrich KN, et al. (2016). Prenatal polybrominated
diphenyl ether and perfluoroalkyl substance exposures and executive function in school-age children. Environmental
Research, 147, 556-564. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26832761
70.	Department of Ecology State of Washington. (2016). Children's Safe Product Act. http://www.ecy.wa.gov/programs/hwtr/
RTT/cspa/
71.	Smith MN GJ, Cullen A, Faustman EM. (2016). Atoxicological framework for the prioritization of children's safe product
act data. International Journal of Environmental Research and Public Health, 13(4), 431. Retrieved from http://www.mdpi.
com/1660-4601 /13/4/431 /htm
72.	UC Berkeley Center for Environmental Research and Children's Health. PBDE flame retardants. 2012; Available from: http://
cerch.org/environmental-exposures/pbde-flame-retardants/
73.	WoodruffTJ, Zota AR and SchwartzJM. (2011). Environmental chemicals in pregnant women in the United States:
NHANES 2003-2004. Environmental Health Perspectives, 119(6), 878-885. Retrieved from https://www.ncbi.nlm.nih.gov/
puhmed/71733055
74.	Harley KG, ChevrierJ, Schall RA, Sjodin A, Bradman A and Eskenazi B. (2011). Association of prenatal exposure to
polybrominated diphenyl ethers and infant birth weight. American Journal of Epidemiology, 174(8), 885-892. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/21878423
75.	US Census Bureau. (2016). Annual estimate of the resident population by sex, age, race, and Hispanic origin for the United
States and States: April 1, 2010 tojuly 1, 2015. https://factfinder.censiJS.gov/faces/tableservices/jsf/pages/prodiJctview.
xhtml?src=bkmk
76.	ChevrierJ, Harley K, Bradman A, Gharbi M, Sjodin A and Eskenazi B. (2010). Polybrominated diphenyl ether (PBDE) flame
retardants and thyroid hormone during pregnancy. Environmental Health Perspectives, 118(10), 1444-1449. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957927/
77.	Harley K, Marks A, ChevrierJ, Bradman A, Sjodin A and Eskenazi B. (2010). PBDE concentrations in women's serum and
fecundability. Environmental Health Perspectives, 118(5), 699-704. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC7866688/
78.	Hawthorne M, Roe S and Callahan P. (2013). California plan could affect toxic flame retardants in products across U.S.
Chicago Tribune. Retrieved from http://articles.chicagotribune.com/2013-02-Q8/news/chi-flame-retardants-california-
plan-20130208 1 flame-retardants-furniture-fires-candle-like-flame
94
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
79.	Center for Environmental Health. (2013). Playing on poisons: Harmful flame retardants in children's furniture. http://www.
ceh.org/wp-content/uploads/2013/11/Kids-Furniture-Report-Press.pdf
80.	Rubin S. (2012). State relies on Salinas study to revise flame retardant regs despite powerful industry lobby. Monterey
County Now. Retrieved from http://www.montereycountyweekly.com/news/local news/state-relies-on-salinas-studv-to-
revise-flame-retardant-regs/article 8a7b7ad7-ed61-5031-8985-9ccfbebfb777.html
81.	Eskenazi B, ChevrierJ, Rauch S, Kogut K, Harley K,Johnson C, Trujillo C, et al. (2013). In utero and childhood polybrominated
diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. Environmental Health Perspectives,
121(2), 257-262. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569691/
82.	Niermann S, Rattan S, Brehm E and FlawsJA. (2015). Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects
reproductive outcomes in female mice. Reproductive Toxicology, 53, 23-32. Retrieved from https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC4457554/
83.	MeekerJD and Ferguson KK. (2014). Urinary phthalate metabolites are associated with decreased serum testosterone in
men, women, and children from NHANES 2011-2012. Thejournal of Clinical Endocrinology & Metabolism, 99(11), 4346-
4352. Retrieved from https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2014-2555
84.	National Academies of Sciences. Phthalates and cumulative risk assessment: The tasks ahead. 2008; Available from: https://
www.nap.edu/catalog/12528/phthalates-and-cumulative-risk-assessment-the-tasks-ahead
85.	Howdeshell KL, Rider CV, Wilson VS, FurrJR, Lambright CR and Grayjr LE. (2015). Dose addition models based on
biologically relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by
a phthalate mixture in rats. Toxicological Sciences, 148(2), 488-502. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/76350170
86.	Pediatric Environmental Health Specialty Units. Consumer guide: Phthalates and bisphenol A. 2014; Available from: http://
www.pehsij.net/ I ibrarv/facts/bpapatients factsheet03-7014.pdf
87.	Clark K, Cousins IT and Mackay D, Assessment of critical exposure pathways, in Series Anthropogenic Compounds. 2003,
Springer, p. 227-262.
88.	Environmental Working Group. Teen girls' body burden of hormone-altering cosmetics chemicals: Detailed findings. 2008;
Available from: http://www.ewg.org/research/teen-girls-body-bijrden-hormone-altering-cosmetics-chemicals/detailed-
findings
89.	Environmental Working Group. Exposures add up- Survey results. 2003; Available from: http://www.ewg.org/
skindeep/2004/06/15/exposures-add-up-survey-results/#.WaillWZMrlV
90.	Ferguson KK, McElrath TF, Cantonwine DE, Mukherjee B and MeekerJD. (2015). Phthalate metabolites and bisphenol-A in
association with circulating angiogenic biomarkers across pregnancy. Placenta, 36(6), 699-703. Retrieved from https://www.
ncbi.nlm.nih.gov/pubmed/25913709
91.	Ferguson KK, McElrath TF, Chen Y-H, Mukherjee B and MeekerJD. (2015). Urinary phthalate metabolites and biomarkers of
oxidative stress in pregnant women: a repeated measures analysis. Environmental Health Perspectives, 123(3), 210-216.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25402001
92.	Barakat R, Lin P-CP, Rattan S, Brehm E, Canisso IF, Abosalum ME, FlawsJA, et al. (2017). Prenatal exposure to DEHP induces
premature reproductive senescence in male mice. Toxicological Sciences, 156(1), 96-108. Retrieved from https://www.ncbi.
nlm.nih.gov/pubmed/78087598
93.	Zhou C, Gao L and FlawsJA. (2017). Prenatal exposure to an environmentally relevant phthalate mixture disrupts
reproduction in F1 female mice. Toxicology and Applied Pharmacology, 318,49-57. Retrieved from http://www.
sciencedirect.com/science/article/pii/S0041008X17300303
94.	Zhou C and FlawsJA. (2016). Effects of an environmentally relevant phthalate mixture on cultured mouse antral follicles.
Toxicological Sciences, 156(1), 217-229. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/78013714
95
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
95.	UC Berkeley Center for Environmental Research and Children's Health. HERMOSA study. 2017; Available from: http://cerch.
berkeley.edu/research-programs/hermosa-study
96.	ABC News, Behind the beauty counter: What's really in your makeup? 2016. http://abcnews.go.com/GMA/video/beauty-
counter-makeup-44050754
97.	NPR. Teen study reveals dangerous chemicals in cosmetics. 2015; Available from: http://www.npr.
org/7015/07/74/476765101 /teen-study-reveals-dangerous-chemicals-in-cosmetics
98.	Yang S. (2016). Teen girls see big drop in chemical exposure with switch in cosmetics. Berkeley News. Retrieved from http://
news.berkeley.edu/2016/03/07/cosmetics-chemicals/
99.	Philippat C, Bennett DH, Krakowiak P, Rose M, Hwang H-M and Hertz-Picciotto I. (2015). Phthalate concentrations in house
dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics
and the Environment (CHARGE) study. Environmental Health, 14(1), 56. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/76108771
100.	Centers for Disease Control and Prevention. National surveillance data (1997-2015). 2016; Available from: https://www.cdc.
gov/nceh/lead/data/national.htm
101.	US Environmental Protection Agency. American's children and the environment: Biomonitoring lead. 2015; Available from:
https://www.epa.gov/ace/ace-biomonitoring-lead
102.	US Department of Housing and Urban Development: Office of Healthy Homes and Lead Hazard Control. (2011). American
healthy homes survey: Lead and arsenic findings. https://portal.hud.gov/hudportal/documents/huddoc%3Fid=AHHS
Report.pdf
103.	Canfield RL, Henderson Jr CR, Cory-Slechta DA, Cox C,JuskoTAand Lanphear BP. (2003). Intellectual impairment in children
with blood lead concentrations below 10 |jg per deciliter. New England Journal of Medicine, 348(16), 1517-1526. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046839/
104.	Yuan W, Holland S, Cecil K, Dietrich K, Wessel S, Altaye M, Hornung R, et al. (2006). The impact of early childhood lead
exposure on brain organization: a functional magnetic resonance imaging study of language function. Pediatrics, 118(3),
971 -977. Retrieved from http://pediatrics.aappublications.Org/content/118/3/971.short
105.	WrightJP, Dietrich KN, Ris MD, Hornung RW, Wessel SD, Lanphear BP, Ho M, et al. (2008). Association of prenatal and
childhood blood lead concentrations with criminal arrests in early adulthood. PLoS Medicine, 5(5), e101. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689664/
106.	Cecil KM, Brubaker CJ, Adler CM, Dietrich KN, Altaye M, EgelhoffJC, Wessel S, et al. (2008). Decreased brain volume in adults
with childhood lead exposure. PLoS Medicine, 5(5), e112. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/18507499
107.	Miranda ML, Kim D, ReiterJ, Galeano MAO and Maxson P. (2009). Environmental contributors to the achievement gap.
Neurotoxicology, 30(6), 1019-1024. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19643133
108.	Lanphear B, Hornung R, KhouryJ, Yolton K, Baghurst P, Bellinger D, Canfield R, et al. (2005). Low-level environmental lead
exposure and children's intellectual function: an international pooled analysis. Environmental Health Perspectives, 113(7),
894-899. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757657/
109.	Huang S, Hu H, Sanchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, et al. (2016). Childhood blood
lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children.
Environmental Health Perspectives, 124(6), 868-704. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26645203
110.	Environmental Protection Agency. Learn about lead. 2017; Available from: https://www.epa.gov/lead/learn-aboiJt-lead
111.	US US Environmental Protection Agency. (2013). Integrated Science Assessment for lead, https://www.epa.gov/isa/
integrated-science-assessment-isa-lead
112.	Children's Environmental Health Network. (2015). A blueprint for protecting children's environmental health: An urget call to
action. http://cehn.org/wp-content/uploads/2015/11/BluePrint Final1.pdf
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
113.	AdgateJL, Barr DB, Clayton CA, Eberly LE, Freeman N, Lioy PJ, Needham LL, et al. (2001). Measurement of children's
exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample. Environmental Health
Perspectives, 109(6), 583-590. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240340/
114.	Berkowitz G, Obel J, Deych E, Lapinski R, Godbold J, Liu Z, Landrigan P, et al. (2003). Exposure to indoor pesticides during
pregnancy in a multiethnic, urban cohort. Environmental Health Perspectives, 111(1), 79-84. Retrieved from https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC1241309/
115.	Brad man MA, Harnly ME, Draper W, Seidel S, Teran S, Wakeham D and Neutra R. (1997). Pesticide exposures to children
from California's Central Valley: results of a pilot study. Journal of Exposure Analysis and Environmental Epidemiology, 7(2),
217-234. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/9185013
116.	Hill RH, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, Williams CC, et al. (1995). Pesticide residues in urine of adults living
in the United States: reference range concentrations. Environmental Research, 71(2), 99-108. Retrieved from https://www.
ncbi.nlm.nih.gov/pubmed/8977618
117.	Loewenherz C, Fenske RA, Simcox NJ, Bellamy G and Kalman D. (1997). Biological monitoring of organophosphorus
pesticide exposure among children of agricultural workers in central Washington State. Environmental Health Perspectives,
105(12), 1344-1353. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9405329
118.	Lu C, Knutson DE, Fisker-AndersenJ and Fenske RA. (2001). Biological monitoring survey of organophosphorus pesticide
exposure among pre-school children in the Seattle metropolitan area. Environmental Health Perspectives, 109(3), 299-303.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11333193
119.	Centers for Disease Control and Prevention. (2009). Fourth national report on human exposure to environmental
chemicals, https://www.cdc.gov/exposurereport/pdf/fourthreport.pdf
120.	Whyatt RM, Camann DE, Kinney PL, Reyes A, Ramirez J, Dietrich J, Diaz D, et al. (2002). Residential pesticide use during
pregnancy among a cohort of urban minority women. Environmental Health Perspectives, 110(5), 507-514. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/12003754
121.	National Research Council. (1993). Pesticides in the diets of infants and children, https://www.nap.edu/catalog/2126/
pesticides-in-the-diets-of-infants-and-children
122.	US Environmental Protection Agency. Pesticides and their impact on children: Key facts and talking points. 2015; Available
from: https://www.epa.gov/sites/production/files/2015-12/documents/pest-impact-hsstaff.pdf
123.	World Health Organization. (1986). Organophosphorous insecticides: A general introduction (Vol. 63). New York: World
Health Organization.
124.	Donald D, KielyT and Grube A. (2002). Pesticides industy sale and usage: 1998 and 1999 market estimates. https://nepis.
epa.POv/Fxe/7yPDF.cpi/700001G5.PDF?Dockey=700001G5.PDF
125.	McCauley LA, Lasarev MR, Higgins G, Rothlein J, MunizJ, Ebbert C and PhillipsJ. (2001). Work characteristics and pesticide
exposures among migrant agricultural families: a community-based research approach. Environmental Health Perspectives,
109(5), 533-538. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1740315/
126.	O'Rourke MK, Lizardi PS, Rogan SP, Freeman NC, Aguirre A and Saint CG. (2000). Pesticide exposure and creatinine variation
among young children. Journal of Exposure Science and Environmental Epidemiology, 10(S1), 672-681. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/11138659
127.	Simcox NJ, Camp J, Kalman D, Stebbins A, Bellamy G, Lee l-C and Fenske R. (1999). Farmworker exposure to
organophosphorus pesticide residues during apple thinning in central Washington State. American Industrial Hygiene
Association Journal, 60(6), 752-761. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10635541
128.	Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell N, Barr D, Furlong C, et al. (2004). Association of in utero
organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environmental
Health Perspectives, 112(10), 1116-1124. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/15738787
97
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
129.	YoungJ, Eskenazi B, Gladstone E, Bradman A, Pedersen L, Johnson C, Barr D, et al. (2005). Association between in utero
organophosphate pesticide exposure and abnormal reflexes in neonates. Neurotoxicology, 26(2), 199-209. Retrieved from
http://www.sciencedirect.com/science/article/pii/S0161813XQ40Q1597
130.	Eskenazi B, Marks A, Bradman A, Fenster L, Johnson C, Barr D and Jewll N. (2006). In utero exposure to
dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment among
young Mexican American children. Pediatrics, 118(1), 233-241. Retrieved from http://pediatrics.aappublications.org/
content/118/1/233.short
131.	Thompson B, Griffith WC, Barr DB, Coronado GD, Vigoren EM and Faustman EM. (2014). Variability in the take-home
pathway: Farmworkers and non-farmworkers and their children. Journal of Exposure Science & Environmental
Epidemiology, 24(5), 522-531. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24594649
132.	Coronado GD, Vigoren EM, Griffith WC, Faustman EM and Thompson B. (2009). Organophosphate pesticide exposure
among pome and non-pome farmworkers: a subgroup analysis of a community randomized trial. Journal of Occupational
and Environmental Medicine, 51(4), 500-509. Retrieved from http://joijrnals.lww.com/joem/Abstract/7009/0400Q/
Organophosphate Pesticide Exposure Among Pome and.14.aspx
133.	Coronado GD, Vigoren EM, Thompson B, Griffith WC and Faustman EM. (2006). Organophosphate pesticide exposure and
work in pome fruit: evidence for the take-home pesticide pathway. Environmental Health Perspectives, 114(7), 999-1006.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513343/
134.	Eskenazi B, Marks A, Bradman A, Harley K, Barr D, Johnson C, Morga N, et al. (2007). Organophosphate pesticide exposure
and neurodevelopment in young Mexican-American children. Environmental Health Perspectives, 115(5), 792-798.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867968/
135.	Marks A, Harley K, Bradman A, Kogut K, Barr D, Johnson C, Calderon N, et al. (2010). Organophosphate pesticide exposure
and attention in young Mexican-American children: the CHAMACOS Study. Environmental Health Perspectives, 118(12),
1768-1774. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002198/
136.	Bouchard M, ChevrierJ, Harley K, Kogut K, Vedar M, Calderon N, Trujillo C, et al. (2011). Prenatal exposure to
organophosphate pesticides and IQ in 7-year-old children. Environmental Health Perspectives, 119(8), 1189-1195. Retrieved
from https://www.ncbi.nlm.nih.gov/pubmed/21507776
137.	Gunier RB, Bradman A, Harley KG, Kogut K and Eskenazi B. (2016). Prenatal residential proximity to agricultural pesticide use
and IQ in 7-year-old children. Environmental Health Perspectives, 125(5), 057002-1-8. Retrieved from https://www.ncbi.nlm.
nih.gov/pubmed/28557711
138.	Bloomberg M. (2009). Personal email.
139.	US Environmental Protection Agency. (2006). Reregistration eligibility decision for chlorpyrifos https://www3.epa.gov/
pesticides/chem search/reg actions/reregistration/red PC-059101 1-lul-06.pdf
140.	Rauh V, Garfinkel R, Perera F, Andrews H, Hoepner L, Barr D, Whitehead R, et al. (2006). Impact of prenatal chlorpyrifos
exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics, 118(6), e1845-e1859.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390915/
141.	Furlong C, Holland N, Richter R, Bradman A, Ho A and Eskenazi B. (2006). PON1 status of farmworker mothers and children
as a predictor of organophosphate sensitivity. Pharamacogenetics and Genomics, 16(3), 183-190. Retrieved from https://
www.ncbi.nlm.nih.gov/pubmed/16495777
142.	Huen K, Harley K, BrooksJ, Hubbard A, Bradman A, Eskenazi B and Holland N. (2009). Developmental changes in PON1
enzyme activity in young children and effects of PON1 polymorphisms. Environmental Health Perspectives, 117(10), 1632-
1638. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790571/
143.	Gonzalez V, Huen K, Venkat S, Pratt K, Xiang P, Harley KG, Kogut K, et al. (2012). Cholinesterase and paraoxonase (PON1)
enzyme activities in Mexican-American mothers and children from an agricultural community. Journal of Exposure Science
& Environmental Epidemiology, 22(6), 641-648. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22760442
-------
ENVIRONMENTAL EXPOSURES
REFERENCES
144.	Brad man A, Salvatore A, Boeniger M, Castorina R, SnyderJ, Barr D, Jewell N, et al. (2009). Community-based intervention to
reduce pesticide exposure to farmworkers and potential take-home exposure to their families. Journal of Exposure Science
and Epidemiology, 19(1), 79-89. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545293/
145.	Salvatore A, ChevrierJ, Bradman A, CamachoJ, LopezJ, Kavanagh-Baird G, Minkler M, et al. (2009). A community-based
participatory worksite intervention to reduce pesticide exposures to farmworkers and their families. American Journal of
Public Health, 99(S3), S578-S581. Retrieved from http://ajph.aphapublications.org/doi/abs/10.2105/AIPI-l.2008.149146
146.	Coronado GD, Holte SE, Vigoren EM, Griffith WC, Barr DB, Faustman EM and Thompson B. (2012). Do workplace and
home protective practices protect farm workers? Findings from the "For Healthy Kids" study. Journal of Occupational and
Environmental Medicine, 54(9), 1163-1169. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866960/
147.	Salvatore AL, Bradman A, Castorina R, CamachoJ, LopezJ, Barr DB, SnyderJ, et al. (2008). Occupational behaviors and
farmworkers' pesticide exposure: findings from a study in Monterey County, California. American Journal of Industrial
Medicine, 51(10), 782-794. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605684/
148.	Salvatore AL, Castorina R, CamachoJ, Morga N, LopezJ, Nishioka M, Barr DB, et al. (2015). Home-based community
health worker intervention to reduce pesticide exposures to farmworkers' children: A randomized-controlled trial. Journal
of Exposure Science and Environmental Epidemiology, 25(6), 608-615. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/76036987
149.	Coronado G, Griffith W, Vigoren E, Faustman E and Thompson B. (2010). Where's the dust? Characterizing locations of
azinphos-methyl residues in house and vehicle dust among farmworkers with young children. Journal of Occupational and
Environmental Hygiene, 7(12), 663-671. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20945243
150.	Thompson B, Coronado G, Vigoren E, Griffith W, Fenske R, Kissel J, ShiraiJ, et al. (2008). Para ninos saludables: a community
intervention trial to reduce organophosphate pesticide exposure in children of farmworkers. Environmental Health
Perspectives, 116(5), 687-694. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18470300
151.	Smith MN, Workman T, McDonald KM, Vredevoogd MA, Vigoren EM, Griffith WC, Thompson B, et al. (2017). Seasonal and
occupational trends of five organophosphate pesticides in house dust. Journal of Exposure Science and Environmental
Epidemiology, 27(4), 372-378. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/77553997
152.	UC Berkeley Center for Environmental Research and Children's Health, Senate Environmental Quality Committee. 2017.
http://senate.ca.gov/media/senate-environmental-quality-committee-20170301/video
153.	Thompson B, Carosso E, Griffith W, Workman T, Hohl S and Faustman E. (2017). Disseminating pesticide exposure results
to farmworker and nonfarmworker families in an agricultural community: A community-based participatory research
approach. Journal of Occupational and Environmental Medicine. Retrieved from http://journals.lww.com/joem/Abstract/
publishahead/Disseminating Pesticide Exposure Results to.98876.aspx
154.	Williams M, Barr D, Camann D, Cruz L, Carlton E, Borjas M, Reyes A, etal. (2006). An intervention to reduce residential
insecticide exposure during pregnancy among an inner-city cohort. Environmental Health Perspectives, 114(11), 1684-1689.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665406/
155.	Kass D, McKelvey W, Carlton E, Hernandez M, Chew G, Nagle S, Garfinkel R, et al. (2009). Effectiveness of an integrated pest
management intervention in controlling cockroaches, mice, and allergens in New York City public housing. Environmental
Health Perspectives, 117(8), 1219-1225. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771864/
156.	The NewYorkCity Council. Availability of a computerized service to facilitate notification requirements pursuant
to the pesticide neighbor notification law. 2006; Available from: http://legistar.council.nyc.gov/LegislationDetail.
aspx?ID=450151 &GI )lD=A71 C13D7-RFD3-4655-RA70-RRD11C1AF5AR
157.	New York City Department of Health and Mental Hygiene Bureau of Environmental Surveillance and Policy, Local Law 37 of
2005: Integrated Pest Management Plan. 2007. https://a816-healthpsi.nyc.gov/H37/pdf/IPM 2006.pdf
158.	New York City Department of Health and Mental Hygiene Bureau of Environmental Surveillance and Policy, An update on
integrated pest management in New York City. 2009. https://a816-healthpsi.nyc.gov/H37/pdf/IPM 2006.pdf
-------
REFERENCES
ENVIRONMENTAL EXPOSURES
159.	National Cancer Institute. Secondhand smoke and cancer. 2011; Available from: https://www.cancer.gov/ahoiJt-cancer/
causes-prevention/risk/tobacco/second-hand-smoke-fact-sheet
160.	Ashford KB, Hahn E, Hall L, Rayens MK, Noland M and FergusonJE. (2010). The effects of prenatal secondhand smoke
exposure on preterm birth and neonatal outcomes. Journal of Obstetric, Gynecologic, & Neonatal Nursing, 39(5), 525-535.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951768/
161.	Li Y-F, Langholz B, Salam M and Gilliland F. (2005). Maternal and grandmaternal smoking patterns are associated with early
childhood asthma. CHEST, 127(4), 1232-1241. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15821200
162.	Gilliland F, Islam T, Berhane K, Gauderman W, McConnell R, Avol E and Peters J. (2006). Regular smoking and asthma
incidence in adolescents. American Journal of Respiratory and Critical Care Medicine 174(10), 1094-1100. Retrieved from
http://www.atsjoijrnals.org/doi/abs/10.1164/rccm.700605-777GC
163.	Wenten M, Berhane K, Rappaport EB, Avol E, Tsai W-W, Gauderman WJ, McConnell R, et al. (2005). TNF-308 modifies the
effect of second-hand smoke on respiratory illness-related school absences. American Journal of Respiratory and Critical
Care Medicine, 172(12), 1563-1568. Retrieved from https://www.ncbi.nlm.nih.gOv/pijbmed/16166671
164.	Slotkin T, CardJ, Stadler A, Levin E and Seidler F. (2014). Effects oftobacco smoke on PC12 cell neurodifferentiation are
distinct from those of nicotine or benzo[a]pyrene. Neurotoxicology and Teratology, 43,19-24. Retrieved from http://www.
sciencedirect.com/science/article/pii/S0892036214000269
165.	Slotkin TA, Skavicus S, CardJ, Stadler A, Levin ED and Seidler FJ. (2015). Developmental neurotoxicity oftobacco smoke
directed toward cholinergic and serotonergic systems: more than just nicotine. Toxicological Sciences, 147(1), 178-189.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26085346
166.	Slotkin TA, Skavicus S, Card J, Levin ED and Seidler FJ. (2015). Amelioration strategies fail to prevent tobacco smoke effects
on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors. Toxicology, 333, 63-75. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466707/
167.	Federal Interagency Forum on Child and Family Statistics. (2016). America's children in brief: Key national indicators of well-
being, 2016. https://www.childstats.gov/pdf/ac2016/ac 16.pdf
168.	Metayer C, Zhang L, WiemelsJL, Bartley K, Schiffman J, Ma X, Aldrich MC, et al. (2013). Tobacco smoke exposure and the risk
of childhood acute lymphoblastic and myeloid leukemias by cytogenetic subtype. Cancer Epidemiology and Prevention
Biomarkers, 22(9), 1600-1611. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23853208
169.	de Smith AJ, Kaur M, Gonseth S, Endicott A, Selvin S, Zhang L, Roy R, et al. (2017). Correlates of prenatal and early-life
tobacco smoke exposure and frequency of common gene deletions in childhood acute lymphoblastic leukemia. Cancer
Research, 77(7), 1674-1683. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/78707519
100
-------
HALLMARK FEATURES
REFERENCES
1.	National Institutes of Health and US Environmental Protection Agency. RFA-ES-14-002: Children's Environmental Health
and Disease Prevention Research Centers (P50). 2014; Available from: https://grants.nih.gov/grants/guide/rfa-files/RFA-
FS-14-007.html
2.	UC San Francisco Program on Reproductive Health and the Environment. Information for families: All that matters. 2016;
Available from: https://prhe.iJcsf.edij/info
3.	Dartmouth Children's Center. Arsenic tool. 2015; Available from: http://www.dartmoiJth.edij/~childrenshealth/arsenic/
4.	University of Southern California Environmental Health Centers. Infographics. 2015; Available from: http://envhealthcenters.
usc.edu/infographics
5.	The American College of Obstetricians and Gynecologists. (2013). Exposure to toxic environmental agents. Fertility and
sterility 100(4), 931-934. Retrieved from https://www.ac0g.0rg/-/media/Committee-Opinions/Committee-on-Health-Care-
for-Underserved-Women/co575.pdf
6.	Di Renzo GC, ConryJA, Blake J, DeFrancesco MS, DeNicola N, Martin JN, McCue KA, et al. (2015). International Federation
of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals.
International Journal of Gynecology & Obstetrics, 131(3), 219-225. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/26433469
7.	Miller M, Schettler T, Tencza B, Valenti MA, Agency for Toxic Substances and Disease Registry, Collaborative on Health and
the Environment, Science and Environmental Health Network, UC San Francisco Pediatric Environmental Health Specialty
Unit, A story of health. 7016. https://wspehsu.ucsf.edu/for-clinical-professionals/training/a-story-of-health-a-multi-media-
ebook/
8.	National Jewish Health. Clean air projects- Lesson plan packets, n.d. Available from: https://www.nationaljewish.org/cehc/
lesson-plan-packets
9.	UC San Francisco School of Nursing's California Childcare Health Program, UC Berkeley's Center for Children's
Environmental Health Research, UC Statewide IPM Program and California Department of Pesticide Regulation. Integrated
pest management: A curriculum for early care and education programs. 2011; Available from: http://cerch.berkelev.edu/
sites/default/files/ipm curriculum final 10.7010.pdf
10.	UC San Francisco School of Nursing's Institute for Health & Aging, UC Berkeley's Center for Children's Environmental Health
Research, Informed Green Solutions and California Department of Pesticide Regulation. Green cleaning, sanitizing, and
disinfecting: A curriculum for early care and education. 2013; Available from: http://cerch.berkelev.edu/sites/default/files/
green cleaning toolkit.pdf
11.	UC Berkeley Center for Environmental Research and Children's Health. Providing IPM services in schools and child care
settings. 2016; Available from: http://ipm.ucanr.edu/training/
12.	Zoni S and Lucchini RG. (2013). Manganese exposure: cognitive, motor and behavioral effects on children: a review of
recent findings. Current Opinion in Pediatrics, 25(2), 255-260. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC4073890/
13.	Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B and Smith D. (2012). Determining fetal manganese exposure
from mantle dentine of deciduous teeth. Environmental Science and Technology, 46(9), 5118-5125. Retrieved from http://
pubs.acs.org/doi/abs/10.1071/es703569f
14.	Dutmer CM, Schiltz AM, Faino A, Rabinovitch N, Cho S-H, Chartier RT, Rodes CE, et al. (2015). Accurate assessment of
personal air pollutant exposures in inner-city asthmatic children.Journal of Allergy and Clinical Immunology, 135(2), AB165.
Retrieved from http://www.jacionline.org/article/S0091-6749n4lQ3259-X/abstract
15.	Dutmer CM SA, Faino A, Cho SH, Chartier RT, Rodes CE, Szefler SJ, Schwartz DA, ThornburgJW, Liu AH. (2015). Increased
asthma severity associated with personal air pollutant exposures in inner-city asthmatic children. American Journal of
Respiratory and Critical Care Medicine, 191, A6268. Retrieved from http://www.atsjournals.org/doi/abs/10.1164/ajrccm-
conference.2015.191.1 MeetingAbstracts.A6268
101
-------
REFERENCES
HALLMARK FEATURES
16.	Landrigan P and Etzel R, New Frontiers in Children's Environmental Health, in Textbook of Children's Environmental Health,
P. Landrigan and R. Etzel, Editors. 2014, Oxford University Press: New York, NY. p. 560.
17.	Rappaport SM, Barupal DK, Wishart D, Vineis P and Scalbert A. (2014). The blood exposome and its role in discovering
causes of disease. Environmental Health Perspectives, 122(8), 769-774. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4173034/
18.	Rappaport SM, Li H, Grigoryan H, Funk WE and Williams ER. (2012). Adductomics: characterizing exposures to reactive
electrophiles. Toxicology Letters, 213(1), 83-90. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21501670
19.	Petrick L, Edmands W, Schiffman C, Grigoryan H, Perttula K, Yano Y, Dudoit S, et al. (2017). An untargeted metabolomics
method for archived newborn dried blood spots in epidemiologic studies. Metabolomics, 13(3), 27. Retrieved from https://
link.springer.com/article/10.1007/s11306-Q16-1153-7
20.	Edmands WM, Petrick L, Barupal DK, Scalbert A, Wilson MJ, WickliffeJK and Rappaport SM. (2017). compMS2Miner: An
Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC-MS Data Sets.
Analytical Chemistry, 89(7), 3919-3928. Retrieved from http://pijbs.acs.Org/doi/abs/10.1071/acs.analchem.6b07394
21.	Grigoryan H, Edmands W, Lu SS, Yano Y, Regazzoni L, lava rone AT, Williams ER, et al. (2016). Adductomics pipeline for
untargeted analysis of modifications to Cys34 of human serum albumin. Analytical Chemistry, 88(21), 10504-10512.
Retrieved from http://pubs.acs.Org/doi/abs/10.1021/acs.analchem.6b02553
22.	The National Academy of Sciences. (2017). A review of the Environmental Protection Agency's Science to Achieve Results
Research Program. http://dels.nas.edij/Report/Review-Fnvironmental-Protection/74757
23.	GoodrichJM, Dolinoy DC, Sanchez BN, Zhang Z, MeekerJD, Mercado-Garcia A, Solano-Gonzalez M, et al. (2016). Adolescent
epigenetic profiles and environmental exposures from early life through peri-adolescence. Environmental Epigenetics, 2(3),
dvw018. Retrieved from https://academic.oijp.com/eep/article/7415066/Adolescent-epigenetic-profiles-and-environmental
24.	Goodrich J, Sanchez B, Dolinoy D, Zhang Z, Hernandez-Avila M, Hu H, Peterson K, et al. (2015). Quality control and statistical
modeling for environmental epigenetics: a study on in utero lead exposure and DNA methylation at birth. Epigenetics, 10(1),
19-30. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25580720
25.	Marchlewicz EH, Dolinoy DC, Tang L, Milewski S, Jones TR, GoodrichJM, Soni T, et al. (2016). Lipid metabolism is associated
with developmental epigenetic programming. Scientific Reports, 6, 34857. Retrieved from https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC5054359/
26.	Griffith W, Curl C, Fenske R, Lu C, Vigoren E and Faustman E. (2011). Organophosphate pesticide metabolite levels in pre-
school children in an agricultural community: within- and between-child variability in a longitudinal study. Environmental
Research, 111(6), 751-756. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/71636087
27.	Smith MN, Griffith WC, Beresford SA, Vredevoogd M, Vigoren EM and Faustman EM. (2014). Using a biokinetic model to
quantify and optimize Cortisol measurements for acute and chronic environmental stress exposure during pregnancy.
Journal of Exposure Science and Environmental Epidemiology, 24(5), 510. Retrieved from https://www.ncbi.nlm.nih.gov/
puhmed/74301353
28.	Peterson BS, Rauh VA, Bansal R, HaoX, Toth Z, Nati G, Walsh K, et al. (2015). Effects of prenatal exposure to air pollutants
(polycyclic aromatic hydrocarbons) on the development of brain white matter, cognition, and behavior in later childhood.
JAMA Psychiatry, 72(6), 531-540. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/75807066
29.	Kimmel CA, Collman GW, Fields N and Eskenazi B. (2005). Lessons learned for the National Children's Study from
the National Institute of Environmental Health Sciences/US Environmental Protection Agency Centers for Children's
Environmental Health and Disease Prevention Research. Environmental Health Perspectives, 113(10), 1414-1418. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781790/
30.	Gonzalez-Cossio T, Peterson KE, Sanfn L-H, Fishbein E, Palazuelos E, Aro A, Hernandez-Avila M, et al. (1997). Decrease
in birth weight in relation to maternal bone-lead burden. Pediatrics, 100(5), 856-862. Retrieved from http://pediatrics.
aappublications.org/content/100/5/856.short
102
-------
HALLMARK FEATURES
REFERENCES
31.	Afeiche M, Peterson KE, Sanchez BN, Cantonwine D, Lamadrid-Figueroa H, Schnaas L, Ettinger AS, etal. (2011). Prenatal
lead exposure and weight of 0-to 5-year-old children in Mexico city. Environmental Health Perspectives, 119(10), 1436-1441.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230436/
32.	Zhang A, Hu H, Sanchez B, Ettinger A, Park S, Cantonwine D, Schnaas L, et al. (2012). Association between prenatal lead
exposure and blood pressure in children. Environmental Health Perspectives, 120(3), 445-450. Retrieved from https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC3295346/
33.	Gomaa A, Hu H, Bellinger D, Schwartz J, Tsaih S-W, Gonzalez-Cossio T, Schnaas L, et al. (2002). Maternal bone lead as an
independent risk factor for fetal neurotoxicity: a prospective study. Pediatrics, 110(1), 110-118. Retrieved from http://
pediatrics.aappublications.org/content/110/1/110.short
34.	Hu H, Tellez-Rojo M, Bellinger D, Smith D, Ettinger A, Lamadrid-Figueroa H, Schwartz J, et al. (2006). Fetal lead exposure at
each stage of pregnancy as a predictor of infant mental development. Environmental Health Perspectives, 114(11), 1730-
1735. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665471/
35.	PilsnerJR, Hu H, Wright RO, Kordas K, Ettinger AS, Sanchez BN, Cantonwine D, et al. (2010). Maternal MTHFR genotype and
haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City. The American
Journal of Clinical Nutrition, 92(1), 226-234. Retrieved from http://ajcn.nutrition.Org/content/92/1/226.short
36.	Kordas K, Ettinger A, Bellinger D, Schnaas L, Tellez R, MM, Hernandez-Avila M, Hu H, et al. (2011). A dopamine receptor
(DRD2) but not dopamine transporter (DAT1) gene polymorphism is associated with neurocognitive development of
Mexican preschool children with lead exposure. Journal of Pediatrics, 159(4), 638-643. Retrieved from http://www.
scienced irect.com/science/article/pii/S002234761100299X
37.	Huang S, Hu H, Sanchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, et al. (2016). Childhood blood
lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children.
Environmental Health Perspectives, 124(6), 868-704. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26645203
38.	Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, Romieu I, Peterson KE, AroA, Palazuelos E, et al. (2003). Dietary
calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology,
14(2), 206-212. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/17606887
39.	Ettinger AS, Tellez-Rojo MM, Amarasiriwardena C, Peterson KE, Schwartz J, Aro A, Hu H, et al. (2006). Influence of maternal
bone lead burden and calcium intake on levels of lead in breast milk over the course of lactation. American Journal of
Epidemiology, 163(1), 48-56. Retrieved from https://academic.oup.com/aje/article/163/1/48/85157/lnfluence-of-Maternal-
Bone-Lead-Burden-and-Calcium
40.	Ettinger AS, Lamadrid-Figueroa H, Tellez-Rojo MM, Mercado-Garcia A, Peterson KE, Schwartz J, Hu H, et al. (2009). Effect of
calcium supplementation on blood lead levels in pregnancy: a randomized placebo-controlled trial. Environmental Health
Perspectives, 117(1), 26-31. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677861/
41.	Thomas DB, Basu N, Martinez-Mier EA, Sanchez BN, Zhang Z, Liu Y, Parajuli RP, et al. (2016). Urinary and plasma fluoride
levels in pregnant women from Mexico City. Environmental Research, 150, 489-495. Retrieved from http://www.
scienced irect.com/science/article/pii/S0013935116302808
42.	Moynihan M, Peterson KE, Cantoral A, Song PX, Jones A, Solano-Gonzalez M, MeekerJD, et al. (2017). Dietary predictors of
urinary cadmium among pregnant women and children. Science of The Total Environment, 575,1255-1262. Retrieved from
http://www.sciencedirect.com/science/article/pii/S0048969716321349
43.	Basu N, Tutino R, Zhang Z, Cantonwine DE, GoodrichJM, Somers EC, Rodriguez L, et al. (2014). Mercury levels in pregnant
women, children, and seafood from Mexico City. Environmental Research, 135, 63-69. Retrieved from http://www.
scienced irect.com/science/article/pii/S0013935114002989
44.	YangTC, Peterson KE, MeekerJD, Sanchez BN, Zhang Z, Cantoral A, Solano M, et al. (2017). Bisphenol A and phthalates in
utero and in childhood: association with child BMI z-score and adiposity. Environmental Research, 156, 326-333. Retrieved
from http://www.sciencedirect.com/science/article/pii/S00139351163Q8155
103
-------
REFERENCES
HALLMARK FEATURES
45.	Watkins DJ, Peterson KE, Ferguson KK, Mercado-Garcia A, Tamayoy Ortiz M, Cantoral A, MeekerJD, et al. (2016). Relating
phthaiate and BPA exposure to metabolism in peripubescence: the role of exposure timing, sex, and puberty. The Journal
of Clinical Endocrinology, 101(1), 79-88. Retrieved from https://academic.oup.eom/jcem/article/10171779/2806581/Relating-
Phthalate-and-BPA-Fxposure-to-Metabolism
46.	Watkins DJ, Tellez-Rojo MM, Ferguson KK, LeeJM, Solano-Gonzalez M, Blank-Goldenberg C, Peterson KE, et al. (2014). In
utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. Environmental Research,
134, 233-241. Retrieved from http://www.sciencedirect.com/science/article/pii/S00139351140027Q9
47.	Watkins DJ, Sanchez BN, Tellez-Rojo MM, LeeJM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, et al. (2017).
Phthaiate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and
pubertal development in girls. Environmental Research, 159,143-151. Retrieved from http://www.sciencedirect.com/
science/article/pii/SOOl 3935117309106
48.	Watkins DJ, Sanchez BN, Tellez-Rojo MM, LeeJM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, et al. (2017).
Impact of phthaiate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual
maturation in peripubertal males. Environmental Health, 16(1), 69. Retrieved from https://ehjournal.biomedcentral.com/
articles/10.1186/s17940-017-0778-5
49.	Perng W, Watkins DJ, Cantoral A, Mercado-Garcia A, MeekerJD, Tellez-Rojo MM and Peterson KE. (2017). Exposure to
phthalates is associated with lipid profile in peripubertal Mexican youth. Environmental Research, 154, 311-317. Retrieved
from http://www.sciencedirect.com/science/article/pii/S0013935116310313
50.	Tellez-Rojo M, Bellinger D, Arroyo-Quiroz C, Lamadrid-Figueroa H, Mercado-Garcia A, Schnaas-Arrieta L, Wright R, et al.
(2006). Longitudinal associations between blood lead concentrations lower than 10 microg/dLand neurobehavioral
development in environmentally exposed children in Mexico City. Pediatrics, 118(2), e323-e330. Retrieved from http://
pediatrics.aappublications.org/content/118/2/e323.short
51.	Henn BC, Ettinger AS, SchwartzJ, Tellez-Rojo MM, Lamadrid-Figueroa H, Hernandez-Avila M, Schnaas L, etal. (2010). Early
postnatal blood manganese levels and children's neurodevelopment. Epidemiology (Cambridge, Mass.), 21(4), 433-439.
Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127440/
52.	Tellez-Rojo M, Cantoral A, Cantonwine D, Schnaas L, Peterson K, Hu H and MeekerJ. (2013). Prenatal urinary phthaiate
metabolites levels and neurodevelopment in children at two and three years of age. Science of the Total Environment, 461-
462, 386-390. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/73747553
53.	Watkins DJ, Fortenberry GZ, Sanchez BN, Barr DB, Panuwet P, Schnaas L, Osorio-Valencia E, et al. (2016). Urinary
3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with
child neurodevelopment. Environmental Research, 147, 307-313. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/73747553
54.	Fortenberry G, MeekerJ, Sanchez B, Barr D, Panuwet P, Bellinger D, Schnaas L, et al. (2014). Urinary 3, 5, 6-trichloro-2-
pyridinol (TCPY) in pregnant women from Mexico City: Distribution, temporal variability, and relationship with child attention
and hyperactivity. International Journal of Hygiene and Environmental Health, 217(2-3), 405-412. Retrieved from https://
www.ncbi.nlm.nih.gov/pubmed/240Q1412
55.	Ferguson K, Peterson K, LeeJ, Mercado-Garcia A, Blank-Goldenberg C, Tellez-Rojo M and MeekerJ. (2014). Prenatal and
peripubertal phthalates and bisphenol-A in relation to sex hormones and puberty in boys. Reproductive Toxicology, 47, 70-
76. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/74945889
56.	Afeiche M, Peterson K, Sanchez B, Schnaas L, Cantonwine D, Ettinger A, Solano-Gonzalez M, et al. (2012). Windows of lead
exposure sensitivity, attained height, and body mass index at 48 months. The Journal of Pediatrics, 160(6), 1044-1049.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/77784971
104
-------
REFERENCES
HALLMARK FEATURES
57.	Cantoral A, TellezDRojo MM, Ettinger A, Hu H, HernandezDAvila M and Peterson K. (2016). Early introduction and cumulative
consumption of sugarDsweetened beverages during the preDschool period and risk of obesity at 8-14 years of age.
Pediatric Obesity 11(1), 68-74. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/ijpo.12023/abstract
58.	Perng W, Hector EC, Song PX, Tellez Rojo MM, Raskind S, Kachman M, Cantoral A, et al. (2017). Metabolomic Determinants of
Metabolic Risk in Mexican Adolescents. Obesity. Retrieved from http://onlinelibrary.wiley.com/doi/10.1007/oby.71976/fijll
59.	National Center for Environmental Health/Agency for Toxic Substances and Disease Registry. (2010). Guidelines for the
identification and management of lead exposure in pregnant and lactating women, https://www.cdc.gov/nceh/lead/
publications/leadandpregnancy2010.pdf
60.	Zhou C and Flaws JA. (2016). Effects of an environmentally relevant phthalate mixture on cultured mouse antral follicles.
Toxicological Sciences, 156(1), 217-229. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/78013714
61.	Zhou C, Gao L and Flaws JA. (2017). Prenatal exposure to an environmentally relevant phthalate mixture disrupts
reproduction in F1 female mice. Toxicology and Applied Pharmacology, 318,49-57. Retrieved from http://www.
sciencedirect.com/science/article/pii/S0041008X173003Q3
62.	Wise LM, Sadowski RN, Kim T, Willing J and JuraskaJM. (2016). Long-term effects of adolescent exposure to bisphenol Aon
neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type. Neurotoxicology, 53,186-
192. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808356/
63.	Willing J K, DG; Cortes, LR; Drzewiecki CM; Wehrheim, KE;Juraska,JM. (2016).Long-term behavioral effects of perinatal
exposure to phthatlates and maternal high-fat diet in male and female rates Society for Neuroscience. San Diego, CA.
64.	Kundakovic M, Gudsnuk K, Franks B, MadridJ, Miller R, Perera F and Champagne F. (2013). Sex-specific epigenetic disruption
and behavioral changes following low-dose in utero bisphenol A exposure. Proceedings of the National Academy of
Sciences USA, 110(24), 9956-9961. Retrieved from http://www.pnas.org/content/110/74/9956.short
65.	Kundakovic M and Champagne FA. (2015). Early-life experience, epigenetics, and the developing brain.
Neuropsychopharmacology, 40(1), 141-153. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24917200
66.	Yan Z, Zhang H, Maher C, Arteaga-Solis E, Champagne F, Wu L, McDonald J, et al. (2014). Prenatal polycyclic aromatic
hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) gamma-methylation in offspring, grand-offspring
mice. PLoS ONE, 9(10), e110706. Retrieved from http://joijrnals.plos.org/plosone/article?id=10.1371 /journal.pone.0110706
67.	Miller RL, Yan Z, Maher C, Zhang H, Gudsnuk K, McDonald J and Champagne FA. (2016). Impact of prenatal polycyclic
aromatic hydrocarbon exposure on behavior, cortical gene expression, and DNA methylation of the Bdnf gene.
Neuroepigenetics, 5,11-18. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27088078
68.	Rundle A, Hoepner L, Hassoun A, Oberfield S, Freyer G, Holmes D, Reyes M, et al. (2012). Association of childhood
obesity with maternal exposure to ambient air polycyclic aromatic hydrocarbons during pregnancy. American Journal of
Epidemiology, 175(11), 1163-1172. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491973/
69.	Abreu-Villaga Y, Seidler FJ, Tate CA, Cousins MM and Slotkin TA. (2004). Prenatal nicotine exposure alters the
response to nicotine administration in adolescence: effects on cholinergic systems during exposure and withdrawal.
Neuropsychopharmacology, 29(5), 879-890. Retrieved from https://www.nature.com/npp/journal/v29/n5/pdf/1300401a.pdf
70.	Faulk C, Barks A, Sanchez BN, Zhang Z, Anderson OS, Peterson KE and Dolinoy DC. (2014). Perinatal lead (Pb) exposure
results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course. PLoS ONE, 9(8),
e104273. Retrieved from https://www.ncbi.nlm.nih.gov/pijbmed/75105471
71.	WuJ, Wen XW, Faulk C, Boehnke K, Zhang H, Dolinoy DC and Xi C. (2016). Perinatal lead exposure alters gut microbiota
composition and results in sex-specific bodyweight increases in adult mice. Toxicological Sciences, 151(2), 324-333.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26962054
72.	Faulk C, Liu K, Barks A, Goodrich J and Dolinoy D. (2014). Longitudinal epigenetic drift in mice perinatally exposed to lead.
Epigenetics, 9(7), 934-941. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143408/
105
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REFERENCES
HALLMARK FEATURES
73.	Pizzurro DM, Dao K and Costa LG. (2014). Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth
in primary hippocampal neurons. Toxicology and Applied Pharmacology, 274(3), 372-382. Retrieved from https://www.ncbi.
nlm.nih.gov/pubmed/24342266
74.	Pizzurro DM, Dao K and Costa LG. (2014). Astrocytes protect against diazinon-and diazoxon-induced inhibition of neurite
outgrowth by regulating neuronal glutathione. Toxicology, 318, 59-68. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3999384/
75.	Smith MN, Wilder CS, Griffith WC, Workman T, Thompson B, Dills R, Onstad G, et al. (2015). Seasonal variation in Cortisol
biomarkers in Hispanic mothers living in an agricultural region. Biomarkers, 20(5), 299-305. Retrieved from https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC4850059/
76.	Smith MN, Workman T, McDonald KM, Vredevoogd MA, Vigoren EM, Griffith WC, Thompson B, et al. (2016). Seasonal and
occupational trends of five organophosphate pesticides in house dust. Journal of Exposure Science and Environmental
Epidemiology(27), 372-378. Retrieved from https://www.natijre.com/jes/joijrnal/vaop/ncijrrent/pdf/jes701645a.pdf
77.	Stanaway IB, WallaceJC, Shojaie A, Griffith WC, Hong S, Wilder CS, Green FH, et al. (2017). Human oral buccal microbiomes
are associated with farmworker status and azinphos-methyl agricultural pesticide exposure. Applied and Environmental
Microbiology, 83(2), e02149-16. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27836847
78.	Weldon BA, Shubin SP, Smith MN, Workman T, Artemenko A, Griffith WC, Thompson B, et al. (2016). Urinary microRNAs as
potential biomarkers of pesticide exposure. Toxicology and Applied Pharmacology, 312,19-25. Retrieved from http://www.
sciencedirect.com/science/article/pii/S0041008X16300187
79.	Krewski D, Boekelheide K, Finnell R, Linney E,JacobsonJ, Malveaux F, Ramos K, et al. (2007). Centers of Children's
Environmental Health and Disease Prevention Research Program- Review panel report, https://www.niehs.nih.gov/
research/supported/assets/docs/a c/centers for childrens environmental health and disease prevention research
program review panel report 508.pdf
80.	Bradman A, Castorina R, Boyd Barr D, ChevrierJ, Harnly ME, Eisen EA, McKone TE, et al. (2011). Determinants of
organophosphorus pesticide urinary metabolite levels in young children living in an agricultural community. International
Journal of Environmental Research and Public Health, 8(4), 1061-1083. Retrieved from https://www.ncbi.nlm.nih.gov/
pubmed/21695029
106
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Dan Axelrad, Office of Policy (OP)
Martha Berger, Office of Children's Health Protection (OCHP)
Elaine Cohen-Hubal, Office of Research and Development
(ORD)
Jeffery Dawson, Office of Chemical Safety and Pollution
Prevention (OCSPP), Office of Pesticide Programs (OPP)
Andrew Geller, ORD
Angela Hackel, OCHP
Aaron Ferster, ORD
James Gentry, ORD, National Center for Environmental
Research (NCER)
IntaekHahn, ORD, NCER
Kaythi Han, OCSPP, OPP
James H.Johnson,Jr., ORD, NCER
Annie Kadeli, Office of Environmental Information (OEI)
Rick Keigwin, OCSPP, OPP
APPENDIX A
LIST OF EPA REVIEWERS ¦¦¦¦
Christopher Lau, ORD, National Health and Environmental
Effects Research Laboratory (NHEERL)
Patrick Lau, ORD, NCER
Sylvana Li, ORD, NCER
Danelle Lobdell, ORD, NHEERL
Sarah Mazur, ORD, Immediate Office of the Assistant
Administrator
Jacquelyn Menghrajani, Region 9
Jacqueline Moya, ORD, National Center for Environmental
Assessment (NCEA)
Linda Phillips, ORD, NCEA
Patrick Shanahan, ORD, NCER
Maryann Suero, Region 5
NicolleTulve ORD, National Exposure Research Laboratory
Kelly Widener, ORD, NCER
107
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APPENDIX B
SUMMARY OF GRANTS FUNDED UNDER
THE NIEHS/EPA CHILDREN'S CENTERS PROGRAM, 1998-2017
This appendix summarizes the 46 grants funded as part of the Children's Centers program. Information provided includes:
BRIEF SUMMARY
Environmental exposures and health outcomes studied by each center for each of their awards, as well as the study populations.
GRANT NUMBERS
Use the grant numbers to access annual and final reports as well as publications on the EPA' and NIH2 websites.
PRINCIPAL INVESTIGATORS (PI)
Some Centers have had been led by the same PI for different awards, others have different Pis for each award. Some centers have
also had multiple Pis.
FUNDING INFORMATION
While most centers were funded for 5-year periods, the formative centers were for 3-year periods. These were established in 2010
to expand existing research, stimulate investigation of new research areas, and build capacity in the field of children's environmental
health. You can identify these awards by looking for P20 in the NIH grant numbers.
For more information, please visit the Children's Centers website3.
BROWN UNIVERSITY
Formative Center for the Evaluation of Environmental Impacts on Fetal Development
PI: Kim Boekelheide, M.D., Ph.D.
Study Population: N/A (animal models only)
2010-2014	Focused on correlating biomarkers with exposures to common
$2,174,474	environmental pollutants and stressors. Studied mechanisms that
R834594	explain how environmental toxicants may alter prenatal development.
P20ES018169
Obesity, lung development,
metabolic syndrome
Arsenic, bisphenol A (BPA),
endocrine disrupting
chemicals (EDCs), phthalates
CINCINNATI
Center for the Study of Prevalent Neurotoxicants in Children
PI: Bruce Lanphear, M.D.
Study Population: Pregnant women and their children living in Cincinnati, Ohio
2001-2006
$7,429,010
R829389
P01ES01126
Examined the effects of low-level exposures to prevalent
neurotoxicants. Tested the efficacy of an intervention to reduce lead
toxicity. Evaluated new biomarkers to better predict the adverse effects
of toxicants on cognition. Studied the mechanisms that explain how
potential neurotoxicants contribute to behavioral problems, attention-
deficit hyperactive disorder (ADHD), cognitive deficits, and hearing loss.
Growth, neurodevelopment
Lead, mercury,
polychlorinated biphenyls
(PCBs), secondhand tobacco
smoke (STS), pesticides
1	https://cfpub.epa.gov/ncer abstracts/index.cfm/fuseaction/searchFielded.main
2	https://projectreporter.nih.gov/reporter.cfm
3	https://www.epa.gov/research-grants/niehsepa-childrens-environmental-health-and-disease-prevention-research-
centers
108
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APPENDIX B
COLUMBIA UNIVERSITY
The Columbia Center for Children's Environmental Health
PI: Frederica Perera, Ph.D., Dr.P.H.
Study Population: African-American and Dominican pregnant women and their children in Northern Manhattan and the
South Bronx, New York City
2015-2019
$5,795,207
R836154
P50ES009600
2009-2015
$7,660,669
R834509
P01ES009600
Examining how prenatal and early childhood exposures to air pollution
disrupt brain development and lead to serious cognitive, emotional,
behavioral, and adiposity problems during adolescence. Analyzing
magnetic resonance imaging (MRI) scans to see how early PAH
exposure adversely affects the structure, function, and metabolism of
neural systems known to support the capacity for self- regulation
Studied the role of EDCs in the development of obesity, metabolic
syndrome, and neurodevelopmental disorders in children. Evaluated
the epigenetic mechanisms where prenatal and postnatal exposures to
BPA and PAIHs affect health in adolescence.
2003-2010 Studied mechanisms where prenatal exposures to air pollution may
increase risk of asthma in children aged 5-7. Designed an intervention
and evaluated the efficacy of a comprehensive integrated pest
management (IPM) program for public housing.
$7,947,203
R832141
P01ES009600
1998-2004
$7,080,366
R827027
P01ES009600
Explored the mechanisms where prenatal and postnatal exposures to
air pollutants increase the risk of asthma and/or neurodevelopmental
impairments in young children. Investigated the impact of community
and home-based interventions to reduce toxicant and allergen
exposure, as well as risk of asthma.
ADHD, neurodevelopment,
obesity
Air pollution, polycyclic
aromatic hydrocarbons
(PAIHs)
Neurodevelopment, obesity
Air pollution, BPA, EDCs,
PAHs
Asthma, neurodevelopment
Air pollution, PAHs,
pesticides
Asthma, neurodevelopment
Air pollution, PAHs,
particulate matter (PM), STS
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APPENDIX B
SUMMARY OF GRANTS FUNDED UNDER
THE NIEHS/EPA CHILDREN'S CENTERS PROGRAM, 1998-2017
DARTMOUTH COLLEGE
Children's Environmental Health and Disease Prevention Research Center at Dartmouth
PI: Margaret Karagas, Ph.D.
Study Population: Pregnant women and their children living in New Hampshire whose household is served by a private well
2013-2018
$6,212,622
R835442
P01ES022832
2010-2014
$1,971,577
R834599
P20ES018175
Aims to understand the effect of arsenic and other contaminants in
drinking water and food on child growth, neurodevelopment, and
immune response, including infections, allergy, vaccine response, and
the microbiome. Exploring the relationship between arsenic, gene
expression, and epigenetic alterations in the placenta, and health
outcomes.
Identified sources of arsenic for infants and children living in rural
areas. Studied how arsenic interacts with key pathways in human
development. Identified placental biomarkers related to prenatal
arsenic exposure and to poor health outcomes in children. Determined
the mechanisms that explain how arsenic modulates cell signaling.
Growth, immune function,
neurodevelopment
Arsenic
Immune function, birth
defects
Arsenic
DENVER
Environmental Determinants of Airway Disease in Children
Pi: David Schwartz, M.D.
Study Population: Children nationwide aged 5 to 12 years with asthma
2009-2017
$7,612,686
R834515
PO'I ES018181
Studied whether endotoxin exposure, modified by genetics and
environment, is associated with inflamed airways and more severe
asthma symptoms. Explored whether epigenetic mechanisms
contribute to the etiology of allergic airway disease. Tested an
intervention to reduce home endotoxin levels and improve asthma.
Asthma, immune function,
lung function
Air pollution, endotoxin,
ozone
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Center for Study of Neurodevelopment and Improving Children's Health Following Environmental Tobacco Smoke Exposure
PI: Susan Murphy, Ph.D.
Study Population: Pregnant women and their children living in central North Carolina
2013-2018
$6,110,785
R835437
P01ES022831
Investigating mechanistic relationships between STS exposure and
developmental neurocognitive impairments including ADHD.Exploring
the impact of prenatal and postnatal exposures to environmental
pollutants on neurodevelopmental impairments in both human and
animal models.
ADHD, neurodevelopment
STS
Southern Center on Environmentally-Driven Disparities in Birth Outcomes
Pi: Marie Lynn Miranda, Ph.D.
Study Population: Pregnant women in Durham, North Carolina
2007-2014
$7,735,620
R833293
Determined the mechanisms that explain how environmental, social,
and host factors jointly influence rates of low birthweight, preterm
birth, arid fetal growth restriction iri health disparate populations.
Explored numerous gene- environment interactions in complementary
human and animal models of birth outcomes.
Birth defects, fetal growth
restriction, low birthweight,
preterm birth, respiratory
health
Air pollution, ozone, PM,
non-chemical stressors
EMORY UNIVERSITY
Emory University's Center for Children's Environmental Health
Pis: Linda McCauley, Ph.D., R.N., P. Barry Ryan, Ph.D.
Study Population: Pregnant African American women and their children living in metro Atlanta
2015-2019
$5,023,117
R836153
P50ES026071
Assess pregnant women's environmental exposures, the impact on the
microbiome, and the subsequent effects of changes in the microbiome
on infant and child neurodevelopment.
Microbiome,
neurodevelopment, preterm
birth, socioemotional
development
EDCs, maternal stress,
chemical exposures
111
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APPENDIX B
SUMMARY OF GRANTS FUNDED UNDER
THE NIEHS/EPA CHILDREN'S CENTERS PROGRAM, 1998-2017
HARVARD UNIVERSITY
Metal Mixtures and Children's Health
PI: Howard Hu, M.D., Sc.D., Joseph Brain, S.D. (Co-PI)
Study Population: Children living in the Tar Creek Superfund site of Oklahoma
2003-2010 txamined biological markers of prenatal and early childhood exposures Growth, neurodevelopment
$7,184,280 t0 metals. Explored the potential effect of stress from living near toxic
R831725	waste and the modifying effect of stress on the neurotoxicity of metals, manganese stress
P01ES012874 Used animal models to address fundamental mechanisms of metal
pharmacokinetics.
THE JOHNS HOPKINS UNIVERSITY
Center for the Study of Childhood Asthma in the Urban Environment (CCAUE)
PI: Nadia Hansei, M.D.; Greg Diette, M.D., Patrick Breysse, Ph.D.; Peyton Eggleston, M.D. (reverse chronological order)
Study Population: African-American children with asthma, living in the inner city of Baltimore
2015-2019
$6,000,000
R836152
P01ES018176
2009-2014
$8,180,400
R834510
P01ES018176
2003-2010
$7,125,443
R8232139
P01ES009606
1998-2003
$7,773,787
R826724
P01ES009606
Exploring how exposure to air pollution causes high rates of asthma
in the inner city. Investigating whether obese children with asthma are
more vulnerable to the effects of air pollution. Studying a variety of
mechanisms, including increased inflammation and oxidative stress.
Investigated how diet influences the asthmatic response to indoor and
outdoor air pollution. Studied the mechanisms that explain how a low
anti-oxidant, pro-inflammatory diet impairs the capacity to respond to
oxidative stress, thereby increasing susceptibility to exposures.
Examined how exposures to air pollution and allergens may relate
to airway inflammation and respiratory morbidity in children with
asthma. Explored new ways to reduce asthma symptoms by reducing
environmental exposures. Examined the mechanisms where PM may
exacerbate an allergen-driven inflammatory response in the airways.
Examined the genetic mechanisms for susceptibility to an inflammatory
response in airways generated as a result of exposure to ozone.
Developed intervention strategies to reduce environmental pollutant
and indoor allergen exposures.
Asthma, obesity
Air pollution, nitrogen
dioxide (N02), PM
Asthma
Air pollution, diet
Asthma
Air pollution, PM
Asthma
Air pollution, ozone
3
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m
TV
MOUNT SINAI SCHOOL OF MEDICINE
Inner City Toxicants, Child Growth, and Development
PI: Mary Woiff, Ph.D.; Phiilip Landrigan, M.D.
Study Population: Pregnant African American and Latino women and their children living in inner city New York
2003-2010
$7,919,631
R831711
P01ES009584
1998-2003
$8,007,874
R827039
P01ES009584
Studied children's pathways of exposure to EDCs. Explored
relationships among prenatal and early childhood exposures to EDCs
and neurobehavioral development in children 6 to 10 years old.
Evaluated individual susceptibility factors such as, built environment,
diet, physical activity, and genetic variability.
Identified linkages between environmental toxicants and
neurodevelopmental dysfunction. Studied mechanisms that explain
how environmental toxicants can impair development. Evaluated novel
approaches to prevention.
Neurodevelopment
EDCs, lead, non-chemical
stressors, PCBs, pesticides
Neurodevelopment
EDCs, lead, PCBs, pesticides
NORTHEASTERN UNIVERSITY
Center for Research on Early Childhood Exposure and Development in Puerto Rico
PI: Akram Alshawabkeh, Ph.D.
Study Population: Young children born to mothers living near Superfund and hazardous waste sites in Puerto Rico during
pregnancy
2015-2019
$4,999,537
R836155
P50ES026049
Focusing on the impact of a mixture of environmental exposures on
prenatal and early childhood development in an underserved and
highly-exposed population. Study the mechanisms that explain how
environmental toxicant exposures during pregnancy affect childhood
health and development.
Growth, neurodevelopment,
preterm birth
Air pollution, consumer
products, EDCs, maternal
stress, parabens, water
quality
113
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APPENDIX B
SUMMARY OF GRANTS FUNDED UNDER
THE NIEHS/EPA CHILDREN'S CENTERS PROGRAM, 1998-2017
UNIVERSITY OF CALIFORNIA, BERKELEY
Berkeley/Stanford Children's Environmental Health Center
PI: S. Katharine Hammond, Ph.D. (current);John Balmes, M.D. (Co-PI); Gary Shaw, Dr.P.H. (Co-PI); Ira Tager, M.D.
Study Population: Pregnant women, infants, children, and adolescents living in the San Joaquin Valley and Fresno, California
2013-2018
$7,175,201
R835435
P01ES022849
2010-2014
$1,986,370
R834596
P20ES018173
Understanding the relationship between air pollution and health
outcomes throughout childhood. Examining the modifying role of both
genetic and neighborhood factors. Studying the underlying immune
mechanisms that could be related to environmental exposures and
health outcomes. Improving risk assessment in a region characterized
by both high air pollution and health disparities.
Investigated the effects of prenatal and childhood exposures to
air pollution on birth outcomes, immune function, and asthma.
Studied the underlying immune mechanisms that could be related to
environmental exposures and health outcomes.
Asthma, atopy, birth defects,
diabetes, immune function,
obesity, preterm birth
Air pollution, non-chemical
stressors, PAHs
Asthma, birth defects,
immune function, low birth
weight, preterm birth
Air pollution, endotoxin,
non-chemical stressors,
PAHs
Center for Environmental Research and Children's Health (CERCH)
PI: Brenda Eskenazi, Ph.D.
Study Population: Pregnant women and their children in a primarily low-income, farmworker community in the Salinas
Vailey, California
2009-2017
$6,179,461
R834513
P01ES009605
2003-2010
$8,431,143
R831710
P01 ES009605
1998-2003
$8,695,541
R826709
P01ES009605
Studying exposures and health outcomes in children, focusing on boys
age 9-13 year. Focusing on exposure to a mix of chemicals including
pesticides, PBDE flame retardants, and manganese fungicides.
Assessing the relationship of prenatal and early childhood exposures
with neurodevelopment and the timing of pubertal onset. Studying on
molecular mechanisms with a focus on epigenetic effects.
Assessed exposures and health outcomes in children age 5-7 years.
Conducted specialized pesticide exposure studies to improve
understanding of pesticide metabolism. Conducted laboratory studies
to investigate responses to mixed exposures to pesticides and
allergens.
Explored whether chronic, low-level exposures to organophosphate
pesticides are potentially hazardous to children's health. Initiated and
evaluated the impact of an intervention to reduce pesticide exposure
to children.
Neurodevelopment,
reproductive development
Manganese, PBDEs,
perfluorooctanoic acid
(PFOA), perfluorooctane-
sulfonic acid (PFOS),
pesticides
Asthma, growth,
neurodevelopment
PBDEs, PCBs, pesticides
Asthma, neurodevelopment
Pesticides
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APPENDIX B
UNIVERSITY OF CALIFORNIA, BERKELEY
Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE)
PI: Catherine Metayer, M.D., Ph.D.(current); Patricia Buffler, Ph.D.
Study Population: Children with leukemia living in California and worldwide
2015-2019
$5,999,999
R836159
P50ES018172
Identifying causes of childhood leukemia in an ethnically diverse
population and understand how environmental factors increase risk.
Studying specific chemical exposures during pregnancy and the effects
on immune system development and risk of childhood leukemia.
Investigating the epigenetic mechanisms associated with exposures
and leukemia risk.
2009-2014	Investigated the effects of prenatal and childhood exposures to
$6 667 762	chemicals. Investigated the genetic and epigenetic mechanisms
R834511	associated with exposures and leukemia risk.
P01 ES018172
Leukemia, immune function
PBDEs, PCBs, pesticides, STS
Leukemia, immune function
PBDEs, PCBs, pesticides, STS

Center for Children's Environmental Factors in the Etiology of Autism
PI: Judy Van de Water, Ph.D. (current); Isaac Pessah, Ph.D. and Irva Hertz-Piccioto, Ph.D. (Co-PI)
Study Population: Children iiving in California with autism or developmental delay
2013-2018 Studying the epigenetic mechanisms of toxicant exposure on
$6 061 423 immune function. Develop and apply new biomarkers of autism risk.
R835432	Characterizing the potential health effects of environmental exposures
P01ES011269 anc| varj0US |jfe stages. Predicting long-term clinical and behavioral
consequences.
Autism spectrum disorder
(ASD), immune function
PBDEs, PFOA, PFOS,
pesticides
2006-2013
$8,154,371
R833292
P01ES011269
2001-2006
$7,395,766
R829388
PO'I ES011269
Identified environmental, immunologic, and genetic risk factors
contributing to the incidence and severity of ASD. Studied the
mechanisms that explain how environmental, immunologic, and
molecular factors interact to influence the risk and severity of autism.
Investigated environmental risk factors contributing to the
incidence and severity of autism. Conducted the first case-
controlled epidemiological study of environmental factors in the
etiology of autism. Examined molecular mechanisms underlying
neurodevelopmental disorders associated with autism.
ASD, immune function
Mercury, PBDEs, PCBs
ASD, immune function
Mercury, PBDEs, PCBs
115
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APPENDIX B
SUMMARY OF GRANTS FUNDED UNDER
THE NIEHS/EPA CHILDREN'S CENTERS PROGRAM, 1000-2017
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Pregnancy Exposures to Environmental Chemicals Children's Center
PI: Tracey Woodruff, Ph.D.
Study Population: Pregnant women in northern California
2013-2018
$5,309,618
R835433
P01ES022841
2010-2013
$1,986,370
R834596
P20ES018173
Examining the epigenetic mechanisms that explain how environmental
exposures during pregnancy affect early stages of prenatal
development. Studying how environmental chemicals may damage the
placenta and disrupt prenatal development. Explore whether effects
are exacerbated by maternal stress.
Explored the epigenetic mechanisms that explain how environmental
exposures during pregnancy affect early stages of prenatal
development. Translated scientific findings to healthcare providers
in order to improve clinical care and prevent prenatal exposures to
harmful chemical exposures.
Birth outcomes, early
development, growth,
placental development
BPA, EDCs, non-chemical
stressors, PBDEs,
perflourinated chemicals
(PFCs), PFOA, PFOS
Birth outcomes, early
development, growth,
placental development
BPA, EDCs, non-chemical
stressors
UNIVERSITY OF ILLINOIS
Novel Methods to Assess Effects of Chemicals on Child Development
PI: Susan Schantz, Ph.D.
Study populations: (1) Pregnant women and their infants living in Urbana-Champaign, Illinois; (2) Adolescents living in New
Bedford, Massachusetts
2013-2018
$6,213,565
R835434
P01ES022848
2010-2014
$2,009,214
R834593
P20ES018163
Investigating how EDCs interact with diets high in saturated fat to
impact neurological and reproductive function. Studying the mediating
role of oxidative stress and inflammation. Using laboratory rodent
studies to examine the mechanisms that explain how BPA causes
trans-generational effects on female fertility.
Assessed prenatal and adolescent exposures to BPA and phthalates.
Studied the relationship between environmental exposures, physical
development, cognition, and behavior in infants and adolescents.
Understand the mechanisms where prenatal BPA exposure affects
gonadal development and reproduction in adulthood in mice.
Neurodevelopment,
oxidative stress,
reproductive development
BPA, EDCs, high-fat diet,
phthalates
Growth, neurodevelopment,
reproductive development
BPA, EDCs, phthalates
FRIENDS (Fox River Environment and Diet Study) Children's Environmental Health Center
PI: Susan Schantz, Ph.D.
Study Population: Hmong and Laotian refugees who consume PCB and mercury-contaminated fish from the Fox River in
northeastern Wisconsin
2001-2006 Studied the impact of exposure to PCBs and methylmercury on	Neurodevelopment,
$9,057,170 cognitive, sensory, and motor development. Developed effective	reproductive development
R829390	educational strategies to reduce exposure to neurotoxic contaminants. Mercury PCBs
P01ES011263 Included laboratory rodent studies to better understand the
mechanisms that explain how environmental contaminants may induce
neurological deficits in children.
116
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APPENDIX B
UNIVERSITY OF IOWA
Children's Environmental Airway Disease Center
PI: Gary Hunninghake, M.D.
Study Population: Children 6 to 14 years old living in rural communities in Iowa
1998-2003	Studied mechanisms that initiate, promote, and resolve grain dust- Asthma, respiratory disease
$7,175,201	induced inflammation. Estimated asthma prevalence and morbidity and Endotoxin grain dust
R835435	determine differences between farm and nonfarm children. Discovered
R01ES02234S	that endotoxin increases the replication of viruses iri airway epithelia.
UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY
Center for Childhood Neurotoxicology and Assessment
PI: George Lambert, M.D.
Study Population: Children living in New Jersey with ASD or learning disabilities
2001-2006	Examined the effects of environmental chemicals on neurological
$6,179,461	health and development. Studied brain development in laboratory
R829391	animal models. Explored linkages and the underlying mechanisms
R01ES009605	betWeen environmental neurotoxicants and ASD.
ASD, neurodevelopment
Heavy metals, manganese
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APPENDIX B
SUMMARY OF GRANTS FUNDED UNDER
THE NIEHS/EPA CHILDREN'S CENTERS PROGRAM, 1000-2017
UNIVERSITY OF MICHIGAN
Lifecourse Exposures and Diet: Epigenetics, Maturation and Metabolic Syndrome
PI: Karen Peterson, D.Sc., Vasantha Padmanabhan, Ph.D.
Study Populations: Pregnant and postpartum mothers and their children living in (1) Mexico City and (2) in Michigan
2013-2018
$5,618,006
R835436
P01ES022844
2010-2013
$1,919,311
R834800
P20ES018171
Researching how obesity, sexual maturation, and risk of metabolic
syndrome are affected by the interaction of EDCs with diet during
prenatal development and puberty.
Examined how prenatal and childhood exposures to lead and EDCs
affect the epigenome, the instruction book that programs the activity
of genes, with a focus on key genes regulating growth and maturation;
Examined the associations between prenatal and childhood exposures
to BPA and phthalates, and health outcomes during adolescence.
Birth outcomes, physical
growth, obesity, metabolic
syndrome risk, sexual
maturation
BPA, cadmium, diet, EDCs,
lead, phthalates
Physical growth, obesity,
and sexual maturation
BPA, EDCs, lead, phthalates
Michigan Center for the Environment and Children's Health
PI: Barbara Israel, Dr.P.H.
Study Population: Asthmatic children living in inner city Detroit
1999-2003	Studied environmental hazards in houses and neighborhoods with the Asthma, lung function
$7,433,496	§oa' °f improving asthma-related health. Examined the effects of daily ^jf p0||ution
R826710	and seasonal fluctuations in indoor and outdoor ambient air quality on
P01ES009589	lung function and severity of asthma symptoms.
UNIVERSITY OF SOUTHERN CALIFORNIA
Southern California Children's Environmental Health Center
PI: Robert McConnell, M.D., Frank Gilliland, M.D., Ph.D., Henry Gong, M.D.
Study Population: School-age children living in Los Angeles, California
2013-2018
$6,418,683
R835441
P01ES022845
2003-2010
$7,696,613
R831861
P01ES009581
1998-2003
$7,290,042
R826388
P01ES009581
Investigating the longitudinal effects of prenatal, early and later
childhood TRAP exposure on BMI, obesity, and metabolic dysfunction.
Examining the effects of air pollution on adipose inflammation and
metabolic outcomes.
Examined the effects of regional ambient air pollutants and locally
emitted fresh vehicle exhaust on asthma and airway inflammation.
Assessed genetic variation as a determinant of childhood respiratory
susceptibly.
Explored how host susceptibly and environmental exposures
contribute to children's respiratory disease. Studied the biological
mechanisms that explain how STS alters normal allergic responses in
children.
Fat distribution, insulin
sensitivity, obesity
Air pollution, N02, PM,
traffic-related air pollution
(TRAP)
Asthma, inflammation
Air pollution, N02, PM, TRAP
Asthma, respiratory disease
Air pollution, STS
118
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APPENDIX B
UNIVERSITY OF WASHINGTON
Center for Child Environmental Health Risks Research
PI: Elaine Faustman, Ph.D.
Study Population: Children in agricultural communities in the Yakima Valley region of Washington state
2009-2016
$7,273,531
R834514
P01 ES009601
2003-2010
$7,651,736
R831725
PO'I ES009601
1998-2004
$7,102,390
R826886
P01ES009601
Studied biochemical, molecular and exposure mechanisms that
define children's susceptibility to pesticides. Evaluated age, seasonal,
temporal, and gene-environment factors that define within- and
between-person variability for organophosphate pesticide exposures
and response.
Studied the biochemical, molecular, and exposure mechanisms that
define children's susceptibility to pesticides and the implications for
assessing pesticide risks to normal development and learning.
Studied biochemical, molecular and exposure mechanisms that define
children's susceptibility to pesticides. Developed an intervention to
break the take-home pathway of exposure. Incorporated findings into
risk assessment models designed to protect children's health.
Neurodevelopment
Pesticides
Neurodevelopment
Pesticides
Neurodevelopment
Pesticides
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October 2017
www.epa.gov
U.S. Environmental Protection Agency ¦ Office of Research and Development • National Center for Environmental Research
US. Department of Health and Human Services • National Institutes of Health • National Institutes of Environmental Health Sciences
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