xvEPA
    United States
    Environmental Protection
    Agency
           600S07038
EPA/600/S-07/038 I December 2007 I http://www.epa.gov
                                                                      SUMMARY  REPORT
     Office of Research and Development
     National Center for Environmental Research

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                                                 EPA/600/S-07/038
 A Decade of Children's Environmental Health Research:
Highlights from EPA's Science to Achieve Results Program
                U.S. Environmental Protection Agency
             Office of Research and Development (8101R)
                       http://www.epa.gov
                        December 2007

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Disclaimer

The research described in this document has been funded wholly by the United States Environmental Protection
Agency  (EPA)  under the Science to  Achieve  Results (STAR)  grant program. 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 synthesis 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 sufficiently
detailed nor is it 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.
Acknowledgement

While this document was reviewed by both external and internal EPA reviewers chosen for their contributions to
the field of children's environmental health, it was also reviewed by some of the principal  investigators whose
research is discussed in the report. Dr. Cynthia F. Bearer of Case Western  Reserve University under contract
to ICF International  provided additional review. Rebecca Brown  of EPA's National Center for Environmental
Assessment; Michael Firestone, Ph.D. EPA's Office of Children's Health Protection; Hugh  Tilson, Ph.D. EPA's
Office of Research and Development National Program Director for Human Health reviewed  the report for EPA.

This report was prepared by ICF  International of Fairfax, Virginia under EPA Contract No. 68-C-03-137, Work
Assignments 03-5 and 04-3.

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                                                                         Contents
Glossary	i i
Executive Summary	i
Introduction	2
How This Report is Organized	3
Important Findings Across Life Stages	......	8
    Prenatal: Pollutant Exposure	8
    Neonatal: Genetic Vulnerability	  10
    Infant/Crawler: Early Immune Function	  12
    Toddler: Behaviors that Affect Pollutant Exposure	  14
    Preschooler: Neurological Disorders	  16
    School-Age: Asthma Intervention Programs	,	  18
Children's Health and The Environment: Emerging Trends, Current Work, And Future Directions..  22
    Interpreting Human Biomonitoring Information	'.	  23
    Community-Based Risk Approaches: Exploring Interactions between Chemical
    and Nonchemical Stressors	  23
    Epilogue	  24
Links to Additional Information	25
References                                                                            .  26

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Glossary
Allergic sensitizatiom Process by which a subject becomes increasingly allergic to a substance through
repeated exposure to that substance. As the allergy develops, the response becomes worse with even short
exposures to low concentrations eliciting severe reactions.

Arsenic: Heavy metal naturally occurring in the environment in various organic and inorganic forms. Typical
sources of exposure to arsenic are from food, drinking water, and  pesticides.

Attention  Deficit Hyperactivity Disorder (ADHD): A largely neurological developmental disorder characterized by
a persistent pattern of inattention or hyperactivity-impulsivity, or both.

Autism: A developmental disability that results from a disorder of the human central nervous system.
It is diagnosed using specific criteria for impairments to social interaction, communication, interests,
imagination, and activities.

Autism Spectrum Disorder (ASD): A developmental and behavioral syndrome that results from certain
combinations of characteristically autistic traits.

Biomarken A biological substance (blood,  DNA, saliva, breast milk, hair,  etc.) used to indicate exposure, or
early biological  effect to an environmental chemical, or susceptibility to  disease.

Cell proliferation: Cell growth and multiplication.

CHAMACOS: The Center for the  Health Assessment of Mothers and Children  of Salinas, a project of the
University of California at Berkeley Center for Children's Environmental Health Research.

CHARGE:  Childhood Autism  Risks from Genetics and the Environment, a  project of the University of California
- Davis Center for the Study of  Environmental Factors in the Etiology of Autism.

Chloropyrifos: Ubiquitous organophosphate pesticide widely used before  an  EPA ban on household use
in 2001.

Community-based participatory research (CBPR): A collaborative approach  to research that equitably involves
community and academic investigators in the research process and  recognizes the unique strengths that
each brings, particularly with the goal of achieving social change, to improve health outcomes and eliminate
health disparities.

Detoxify:  Removing harmful substances from  the body through metabolic pathways.

Dichlorodiphenyl dichloroethene (DDE): A metabolite of DDT.

Dichlorodiphenyl trichloroethane (DDT): A synthetic crop pesticide widely used in the 1940s and 1950s and
banned in the 1970s due to its harmful effects on wildlife and proclivity for bioaccumulation.

Environmental neurotoxicants: Naturally occurring (e.g., mercury) or synthetic (e.g., pesticides) chemical
agents that act  specifically  on nerve cells.

Environmental tobacco smoke (ETS): Smoke generated from the burning end of a cigarette, pipe, or cigar and
smoke that is exhaled by smokers.

Exposure assessment: Evaluates the magnitude, frequency, and duration  of human substance exposure.

Genotype: Internally coded,  inherited  information used as a blueprint to build a living organism.

Inorganic arsenic: See arsenic.

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Longitudinal birth-cohort studies: Typically long-term observational studies; often following mothers during
pregnancy and/or babies from birth through several stages of the developmental.
Manganese: Toxic metal similar to iron occurring naturally in the environment; exposure linked to cognitive
and motor impairments.
Metabolites: Biological by-products of metabolism. Often  used as a biomarker to confirm exposure to
environmental factors.
Microactivities: Individual, detailed behavioral characteristics comprising part of the exposure pathway.
Neurotoxic pesticides: Pesticides formulated to alter the normal functioning of the nervous system. See also,
Environmental neurotoxicants.
Ovalbumin (OVA): A protein commonly used in research to stimulate an allergic reaction.
Ozone: An unstable form of oxygen found naturally in the stratosphere and  troposphere. At ground level  it is
considered an air pollutant having harmful effects upon the respiratory system.
Particulate-matter (PM): The summation of airborne molecules, both solid and liquid, that remain suspended
in air. These molecules vary in toxicity due to their size (e.g., PM10,  PM2.5) and /or composition.
Pathways: Refers to the numerous channels by which one can become exposed to environmental pollutants.
Pervasive Developmental Disorder (PDD): A group of five disorders (Autistic Disorder, Rett's Disorder, Childhood
Disintegrative Disorder, Asperger's Syndrome, and Pervasive Developmental Disorder Not Otherwise
Specified) characterized by delays in development.
Pesticide drift: Term used to define the airborne release and distribution of  pesticides/insecticides.
Polybrominated diphenyl ethers (PBDEs): A bioaccumulating flame retardant  substance found  in many
household products (e.g., electronics, furniture).
Polychlorinated biphenyls (PCBs): An  array of synthetic organic pollutants produced primarily for industrial
processes in the 1950-60s and widely  released into the  environment. PCBs were banned in the US in 1977.
Polycyclic aromatic hydrocarbons (PAH): A carcinogenic organic molecule produced from the  burning of
organic substances such as coal, garbage, oil, and cigarettes.
Respiratory syncytial virus (RSV): Virus causing respiratory tract infections, most commonly in infants
and children.
Spray Drift: See pesticide  drift.
T-helper cell (Th1, Th2): A type of T cell that provides help to other cells in  the immune response by
recognizing  foreign antigens and secreting substances called cytokines that activate T  and B cells.
Wheezing: Making a coarse whistling sound due to narrowed or obstructed  air passages; symptomatic of
asthma and/or reduced lung function.

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           EPA/National  Institute of Environmental Health Sciences (NIEHS)
Centers for Children's Environmental Health and Disease Prevention Research Locations
                                     Columbia
                                     University
                                        University of Michigan
       University of Washington
                                University of Iowa
                                                      John Hopkins
                                                        University  \
         UC Davis
       UC Berkeley
University of Illinois
   Urbana-Champaign
                        Cincinnati
                        Children's
                         Hospital
                                                Medical Center
                                                     Harvard
                                                    University

                                                    Mt. Sinai
                                                    Medical
                                                     Center
                                                                           University of
                                                                           Medicine and
                                                                           Dentistry,  NJ
                                                                       Duke
                                                                     University

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Executive  Summary
In 1997, Federal Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks,
mandated Federal agencies to place a high priority on identifying and assessing risks affecting children and to ensure
their policies, standards, and programs address disproportionate risks to children. The Executive Order stimulated
a wide array of research supported by the U.S. Environmental Protection Agency (EPA), particularly through the
National  Center of Environmental Research's (NCER) extramural Science to Achieve Results (STAR) grant program.
In 1998, the.STAR grant program, which supports human health, ecology, economics and engineering sciences through
grants, centers, and fellowships, initiated a diverse portfolio focused specifically on children's environmental health
research.  The goal of this research is to better understand children's genetic, life stage, and behavioral susceptibilities.
The research also aims to better characterize child-specific harmful chemical exposures and to demonstrate cost effective,
protective interventions, particularly at the household and community level. Since 1998, the STAR grant program has
issued more than 10 research solicitations and awarded over 60 grants focusing on children's environmental health,
including: Centers for Children's Environmental Health and Disease Prevention Research (21 Children's Centers
awards—11 currently active); Aggregate Exposure Assessment of Pesticide Exposure (3 grants); Biomarkers for
Children's Risks (8 grants); Children's Vulnerability to Toxics (19 grants);  Children's Valuation (7 grants); and Early
Indicators of Environmentally Related Disease (5 grants). To date, NCER has funded more than a hundred individual
projects resulting in more than a thousand peer-reviewed  articles in a wide array of scientific publications.
Since the passage of the Executive Order  10 years ago, this research has  increased  scientific knowledge of many
aspects of children's environmental health. For example, studies have shed light on how environmental exposures
change across life stages from newborn to school-age children and some of the genetic factors that contribute to
children's vulnerability. Research has also provided insight on how to appropriately assess aggregate and cumulative
exposures, suggested what biological markers in children's urine or blood tell us about exposure or effects, and
indicated what steps need to be taken in order to prevent harmful exposures, including which interventions are effective
and sustainable. This is particularly the case for residential pesticide exposure, which was an articulated focus of the
STAR grant program during the past 10 years. Some of the major research findings include the following:
  • People metabolize pesticides differently based on their genotype; some faster,  others slower. This finding is of
    particular concern during pregnancy, as many babies do not develop the ability to metabolize some pesticides
    during  the first two years of life, putting them at greater risks of health effects.
  • Children living close  to major roadways in Southern California have a higher risk of asthma.
  • EPA's ban on two household pesticides (diazinon and chlorpyrifos) resulted in a rapid decrease in exposures in
    New York City. Children born after the ban were also healthier.
  • Integrated Pest Management (IPM) can be effectively implemented in urban areas to reduce both pesticide and
    allergen triggers.
  • Community partners play a critical role in informing, implementing, and translating children's environmental
    health research.
While much has been discovered  in the last 10 years, there is still much to learn about children's environmental
health. Building on the many lessons learned in characterizing pesticide  exposures during early development and in
investigating the multiple  impacts of indoor and outdoor air pollution on childhood asthma, NCER is now broadening
its focus. Recently, the STAR grant program has increased its support for research on less characterized, though
increasingly common, chemicals (for example, plasticizers and flame retardants) and chronic childhood ailments
(for example, autism and other developmental disabilities). The STAR grant program will continue to work closely
with Federal, state, and community partners to disseminate these and many other findings in order to create healthier
environments and nurture healthier children. The STAR grant program also anticipates continuing, even broadening,
Federal partnerships for future research efforts that build upon the progress that has already been made. For  more
information about NCER  and the STAR grant program, please visit http://www.epa.gov/ncer. For more information
on the Children's Centers, please visit http://www.epa.gov/ncer/childrenscenters.

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 Introduction
Scientists are finding increasing evidence that
exposure to some environmental factors jeopardizes
children's health and may relate to large increases
in the number of children diagnosed with asthma,
Attention Deficit/Hyperactivity Disorder (ADHD),
autism, and developmental impairment. Evidence
is also strong that environmental health risks
disproportionately affect children. Their nervous,
immune, digestive, and other bodily systems are still
developing while they receive disproportionately
greater exposure to pollutants. They eat more food,
drink more fluids, and breathe more air in relation to
their body weight than adults do.
To address the increasingly evident disproportionate
environmental health risks for children, President
Bill Clinton signed Federal Executive Order
13045, Protection of Children from Environmental
Health Risks and Safety Risks, on April 21, 1997
(62 FR 19883). This Order mandated Federal
agencies to place a high priority on identifying and
assessing risks affecting children and to ensure their
policies, programs, activities, and standards address
disproportionate risks to children.
In response, EPA's NCER started a research program
focusing on children's environmental health issues
through its STAR grant program.  In the 10 years
since the Executive Order was signed, NCER has
developed a research portfolio of more  than a
hundred individual projects the results of which have
appeared in more than a thousand peer-reviewed
publications. Policymakers at state and  local levels
have used STAR grant research results to frame
legislation and regulations. These results also
have contributed to various approaches used to
assess risk, and they have provided guidance to
the public in creating safer, healthier environments
(CHPAC-BOSC Workgroup 2007).
In addition, NCER and NIEHS have established the
Centers for Children's Environmental Health and
Disease Prevention Research ("Children's Centers").
This multidisciplinary research effort applies
community-based, participatory research (CBPR)
and innovative techniques in the investigation of
environmental stressors on widespread  childhood
disorders such as asthma, autism, and learning
disabilities. This research is also seeking effective
strategies to reduce children's exposure to these
environmental stressors.
The first eight Children's Centers, established in 1998,
set out to study the effects of environmental factors
such as pesticides and air pollution on childhood
asthma and children's growth and development. In
2001, four more Children's Centers opened to study
the basis of neurodevelopmental and behavioral
disorders such as autism. Additional Children's
Centers began investigations in 2004 and 2007
                                     Neurodevelopmental
                                        Disonias
               CHILDREN'S CENTER
                    RESEARQ^
              Community
              Outreach and
             Transition Core
on how exposure to mixtures of chemicals affects
children's health and which environmental pollutants
cause disparities in birth outcomes. Since 1998, EPA
has awarded 21  Children's Center grants that have
fostered a collaborative network of pediatricians, basic
scientists, epidemiologists, and community advocates
across the United States, seeking to improve the health
and environments of children.
This report highlights some important research
findings from the STAR research grants, including
the Children's Centers during the past 10 years. It also
describes how this scientific research is developing
ways to improve the health of our nation's children.

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                                     How  This  Report  is  Organized
To assist implementation of the 1997 Executive Order,
the EPA Risk Assessment Forum drafted a document,
Guidance on Selecting Age Groups for Monitoring
and Assessing Childhood Exposures to Environmental
Contaminants (Age Grouping Guidance) (EPA 2005)
to complement existing EPA guidance and experience
aimed at improving the accuracy and consistency of
children's exposure assessments. The Age Grouping
Guidance describes logical children's age groupings
for more uniform monitoring studies and exposure
assessments. The document divides age groups
according to specific developmental stages (table 1).


Table 1. Recommended  Childhood Age Groups for
Agency Exposure Assessments (EPA 2005)
Age Groups < 1 Year
Birth to < 1 month
1 to < 3 months
3 to < 6 months
6 to < 12 months
Age Groups > 1 Year
1 to < 2 years
2 to < 3 years
3 to < 6 years
6 to < 1 1 years
1 1 to < 16 years
16 to < 21 years
This summary report uses age groups similar to those
used in the Age Grouping Guidance to illustrate
children's vulnerabilities at different developmental
stages and the disproportionate effects of some
environmental exposures  for children of certain age
groups (table 2). This report combines several age
groups based on similarities of their exposure charac-
teristics. Additionally, it highlights information from
the prenatal lifestage, which is not listed in EPA's Age
Grouping Guidance, yet it does not include the
adolescent life stage (11 to <21 years) because NCER
has yet to fund studies of this age group. Investigators
in the Children's Centers are following children from
birth throughout the various stages of development in
several long-term, longitudinal birth-cohort studies.
    "At EPA, we are committed to protecting
    human health and the environment
    for all our residents, including our
    most vulnerable citizens. By promoting
    children's health research, we are
    working to provide a healthier start for
    every child born in America."
       - Stephen L Johnson, EPA
         Administrator
Highlights of NCER-supported findings in basic
science, exposure assessment, epidemiology, and
intervention for each of the life stages are featured at
the end of this section (table 3). The chapters that
follow report six case studies illustrating that
childhood is a significantly vulnerable period for
exposure to environmental factors and that health
outcomes can vary with a child's age at exposure.
Although the research studies often span multiple life
stages, each case study focuses on susceptibility,
health outcomes, or interventions at one of the six life
stages. Case studies discuss research findings and their
implications for public policy in the following
key issues:
  • Fetal vulnerability, growth, and development
    related to prenatal pollutant exposure
  • Genetic differences in newborns that may
    contribute to susceptibility
  • Immune development, allergic sensitization, and
    allergic and chemical response during the infant
    and crawler life stage
  • The effect a toddler's behavior has on exposure
    to pollutants
  • Autism, autism spectrum disorder (ASD), and
    ADHD as health outcomes of pollutant exposure
  • The effectiveness of various asthma intervention
    programs
References to published results in the scientific literature
are provided throughout the report and in the References
section. In instances where research results have not
yet been published, EPA grant numbers (e.g., R831710)
have been provided. Full information on these grants
may be found by visiting http://www.epa.gov/ncer and
performing a search on the relevant grant number.

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Table 2. Definition of Life Stages and Examples of Exposure Characteristics (EPA 2005)
    Life Stage
  Age
 Group
Characteristics
  Relevant to
 Oral and Der-
 mal Exposure
Characteristics
  Relevant to
  Inhalation
   Exposure
Anatomy and Physiology Characteristics
                    Before
                     Birth
        '
Birth to <
3 months
                               • Breast and
                                 bottle feeding
                               • Hand-to-
                                 mouth activity
                              • Time spent
                               sleeping
                              •Time spent
                               sedentary
                                   • Rapid growth and weight gain
                                   • Increased proportion of body fat
                                   • Increased skin permeability
                                   • Deficiencies in liver enzyme activity (af-
                                     fecting ability to breakdown chemicals)
                                   • Immature immune system functions
                                   • High oxygen requirements (increased
                                     inhalation rates)
                                   • More alkaline stomach fluids (affecting
                                     function and digestion)
                                   • Increased extracellular fluid
                                   • Less kidney function than predicted by
                                     surface area
       £
                    3 to<6
                    months
                   6 to < 12
                    months
              Introduction
              of solid food
             1 Increased
              contact with
              surfaces
             • Increased
              object and
              hand-to-
              mouth activity
            • Expanded
              food
              consumption
            • Increased
              floor mobil-
              ity (surface
              contact)
            • Increased
              likelihood to
              put nonfood
              items in
              mouth
                                                 • Breathing
                                                  zone close to
                                                  the floor
                  • Development
                    of personal
                    dust clouds
                                   • Rapid growth and weight gain
                                   • Increased proportion of body fat
                                   • Deficiencies in liver enzyme activity
                                   • Immature immune system functions
                                   • Increased extracellular fluid
                                   • Kidney function less than predicted by
                                     surface area
                  • Rapid growth and weight gain
                  • Increased body fat begins to level off
                  • Deficiencies in liver enzyme activity (af-
                    fecting ability to breakdown chemicals)
                  • Immature immune system functions
                  • Rapid decrease in extracellular fluid
                  • Kidney function more predictable by
                    surface area

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    Life Stage
   Age
  Group
Characteristics
  Relevant to
 Oral and Der-
 mal Exposure
Characteristics
  Relevant to
  Inhalation
   Exposure
Anatomy and Physiology Characteristics
                     12 to
                     <24
                    months
            • Consumption
              of full range
              of foods
            • Participation
              in increased
              play activity
            • Demonstration
              of curiosity
              accompanied
              with poor
              judgment
            • Cessation of
              breast and
              bottle feeding
                  • Walking
                    upright,
                    running, and
                    climbing
                  • Occupy wider
                    variety of
                    breathing
                    zones
                  • Engage in
                    more vigorous
                    activities
                  1 to < 3 years":
                  • Some liver enzyme activities peak, then
                    fall back to adult range
                  • Most immune system functions mature
                  • Extracellular fluid more consistently
                    related to body size

2 to<6
years



• Onset of
wearing
adult-style
clothing
• Decreased
hand-to-
mouth
activities
• Increased
time outdoors




                                                                    3 to < 8/9 years":
                                                                    • Relatively stable weight gain and
                                                                     skeletal growth (as opposed to a period
                                                                     marked by growth spurts)
                                • Decreased
                                 oral contact
                                 with hands
                                 and objects
                                • Decreased
                                 dermal
                                 contact with
                                 surfaces
                                Time spent
                                in school
                                environments
                                    8/9 to < 16/18 years":
                                    • Rapid skeletal growth
                                    • Rapid reproductive and endocrine
                                      system changes, including puberty
6 to <  11
  years
  Participation
  in sports
  activities
a This life stage was not addressed in EPA's Age Grouping Guidance.
b The age categorization of anatomy and physiology characteristics differs slightly from the age categorization for
behavioral development.

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Table 3. Summary of Relevant Research Findings Across Life Stages
                                       Neonatal: Birth to <3 months
                                              Infant/Crawler
 • Babies exposed before birth to
   higher levels of organophos-
   phate (OP) insecticides have a
   shorter gestation period, smaller
   birth weight, shorter length, and
   decreased head circumference,
   and show delay in neurodevelop-
   ment up to age 3 (R827039C004,
   R831710C001). For example,
   babies exposed prenatally to chlo-
   rpyrifos and diazinon weighed
   less at birth  by an average of 6.6
   ounces, which is equivalent to that
   seen in babies born to women
   who smoked during pregnancy
   (R827027C003).
 • Approximately 40 percent of
   babies exposed before their birth  '
   to a mixture of polycyclic aro-
   matic hydrocarbons (PAHs) primar-
   ily from traffic sources and envi-
   ronmental tobacco smoke (ETS)
   have genetic damage that can be
   linked with increased cancer risk
   (R827027C003).
 • Increases in maternal levels of
   dichlorodiphenyl trichloroethane
   (DDT), a pesticide, during preg-
   nancy decrease scores on the
   Mental Development Index at 2
   years of age. Each 10-fold increase
   in DDT level is associated with a 2-
   to 3-point decrease in mental devel-
   opment (R831710C001).
 • Prenatal exposure to lead or
   tobacco smoke has been implicated
   as a precursor of Attention Deficit/
   Hyperactivity Disorder (ADHD) in
   children, possibly accounting for
   as many as  one in three cases of
   ADHD in children (R829389).
 • Maternal levels of ortho-substituted
   polychlorinated biphenyls (PCBs),
   one form of the class of compounds
   that compose PCBs,  are associated
   with reduced weight gain up to 17
   years of age in girls but not boys,
   suggesting that prenatal exposure
   to PCBs may affect female growth
   (R831711).
• Human respiratory syncytial virus
  (RSV) infection in the first year of
  life increases the risk of asthmatic
  symptoms later in life. RSV affects
  the receptors in the airway that
  interact with environmental agents,
  which may explain why children
  with RSV-induced asthma are espe-
  cially sensitive to their environment
  (R826711003).
• Very low expression of the paraoxo-
  nasel (POND enzyme, an enzyme
  that facilitates the breakdown of
  pesticides into a less toxic form,
  is a major predictor of young chil-
  dren's susceptibility to the toxic
  effects of some OP insecticides
  (R831709).  For example, decreases
  in the PON1 gene cause some new-
  borns to be 26 to 50 times more
  susceptible to adverse health out-
  comes from  exposure to certain
  OP pesticides than other newborns
  (R831710C003).
• Rat pups exposed to  PCBs at the
  same level as babies  breast-fed by
  mothers who live in high-PCB envi-
  ronments have developmental and
  auditory abnormalities, specifically,
  the ability for the brain to interpret
  auditory cues (R829388C005).
• Children in farmworker families
 may be particularly vulnerable to
 pesticides because they often are
 exposed to these chemicals from
 multiple pathways such as pesticide
 drift from agricultural fields, take-
 home exposure from their parents,
 and breast milk from mothers who
 work or have worked in the fields
 (Bradman et al. 2007; R831710).
• Children living within 75 meters of
 a major roadway have an increased
 risk of developing asthma. This
 effect was stronger in girls and in
 children without a family history of
 asthma (R831861).
• Early life exposures to traffic-related
 pollutants in urban environments
 appear to affect the immune system
 by  increasing allergic responses,
 which can lead to respiratory symp-
 toms in children as young as 2
 years of age (Al-alem et al. 2006;
 R827027).
• Developmental exposure to non-
 coplanar PCBs, one of the  many
 forms of compounds that compose
 the class of PCBs, increases the
 chance of a seizure. PCB exposure
 for autistic children is particularly
 dangerous because these children
 have a particularly high rate (about
 30 percent) of seizure disorders
 (R829388).
• Placental tissues with higher
 concentrations of dichlorodiphenyl
 dichloroethene (DDE), a  pesticide
 breakdown product, showed a
 correlation with increased levels of
 type 2 T-helper cells (Th2) cytokines
 (R830825). Elevated levels of these
 cells in  very young children are a
 possible indicator for the develop-
 ment of asthma and other immune
 system  disorders.

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                                                                              School-Age: 6 to <11 years
    Preschooler: 2 to <6 years
 • About 30 percent of children with
   Autistic Spectrum Disorder (ASD)
   exhibit loss of neurological and
   behavioral function during their first
   few years of life (12 to 30 months
   of age). This loss coincides with
   the onset of children's physical
   capacity to explore their environ-
   ment, and, combined with repet-
   itive behavior typical of ASD, it
   increases their exposure to environ-
   mental neurotoxicants. Autistic chil-
   dren also appear to have a different
   genetic or biochemical susceptibility
   (R829391).
 • Toddlers in farmworker communi-
   ties accumulate more pesticides
   on their clothing (socks and union
   suits) compared with younger,
   crawling children. In addition, tod-
   dlers show higher urinary metabolite
   levels than infants (R826709C003).
 • Pesticide levels on children's
   hands are associated with pesti-
   cide metabolite levels in their urine,
   which means that their frequent
   hand-to-mouth behavior may cause
   them to ingest chemicals that they
   come in contact with (R827440).
 • Exposure to lead during early child-
   hood increases the risk of illegal
   behavior as an adult. There is a
   relationship between neuropsycho-
   logical functioning in adolescence
   and police contacts in early adult-
   hood, indicating a link between
   early lead exposure and adult anti-
   social activities (R829389C004).
 • Children with iron deficiency
   retain more lead in their bodies.
   Childhood iron deficiency modifies
   behavior such as increasing pica
   (the desire to eat substances not
   normally eaten) and hand-to-mouth
   activity. These modified behaviors
   can increase children's exposure
   to environmental lead. Correlation
   between iron deficiency and blood
   lead levels is strongest among chil-
   dren aged 1 to 2 years (Bradman et
   al. 2001; R826709C003).
• Mouse allergen exposure and
  asthma-related outcomes have
  a strong and consistent relation-
  ship. Children with high expo-
  sure to mouse allergens have more
  asthma-related unscheduled doctor
  visits, emergency department visits,
  and hospitalization than unexposed
  children (R832139C001).
• Elevated indoor particulate matter
  (PM) levels are associated with
  increased respiratory symp-
  toms in preschool-aged children
  (R832139C001).
• Children with organic diets show
  lower median OP metabolite levels
  in their urine than children with
  conventional diets (Curl et al. 2003;
  R825171).
• Boys who spend the greatest
  amount of time playing outdoors
  have the highest pesticide expo-
  sure levels of any childhood group.
  Similarly, children who play exten-
  sively in  laundry rooms and entry-
  ways exhibit  higher rates of pesti-
  cide metabolites in urine than those
  who do not play, or play less, in
  these areas. Additionally, frequent
  hand washing does little to reduce
  children's pesticide exposures in
  households where chemical con-
  tamination is readily accessible
  (R827443).
• Floor dust appears to be the major
  source of exposure to OPs for young
  children  (accounting for 68.8 per-
  cent), followed by solid food (18.8
  percent) and beverages (10.4 per-
  cent). Air and water contribute less
  than 2 percent to the total aggre-
  gate exposure (R825169).
• Autistic children showed higher
  levels of  leptin (a hormone that
  affects the regulation of body
  weight, metabolism, and repro-
  ductive function, and influences
  the immune system) in their blood
  when compared to typically devel-
  oping children (Ashwood et al.
  2007; R829388C002).
• An increased risk of respiratory-
  related school absences occurs in
  asthmatic and nonasthmatic chil-
  dren exposed to ETS (Gilliland et al.
  2003; R831861).
• Placing air cleaners contain-
  ing high-efficiency particulate air
  (HEPA) filters in inner-city asthmatic
  children's bedrooms can achieve
  a substantial, sustained improve-
  ment in indoor PM levels, one major
  cause of respiratory problems in
  children (Eggleston etal. 2005;
  R832139C002).
• Rural lifestyles may not protect chil-
  dren against developing asthma.
  Prevalence of asthma in rural areas
  is comparable to prevalence in large
  Midwestern cities (R826711C001).
• High levels of PM and ozone are
  associated with worsening pulmo-
  nary function and increased asth-
  matic symptoms among chil-
  dren from  Detroit, Michigan/who
  have moderate to severe asthma
  (R826710C002).
• Disadvantaged  asthmatic chil-
  dren in urban areas appear to be
  at increased risk for higher residen-
  tial allergen levels, elevated air-pol-
  lution exposure, and higher levels
  of asthma triggers in the home
  (Breysse etal. 2005; R832139).
• Children exposed to manga-
  nese and arsenic in the environ-
  ment score lower on general intel-
  ligence tests and tests for memory
  (Wright et al. 2006; R831725).
References to published results in the scientific literature are provided throughout the report and in the References section. In
instances where research results have not yet been published, EPA grant numbers (e.g., R831710) are provided. Full informa-
tion on these grants may be found by visiting httpyAvww.epa.gov/ncer and performing a search on the relevant grant number.

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 Important   Findings  Across  Life  Stages
The six case studies in this section of the report
highlight NCER-supported findings for each of the six
life stages (table 2).
Every day, people are exposed to many different
environmental pollutants ranging from pesticides used
to control cockroaches in the home to particulate
matter (PM) generated from combustion engines in
vehicles. Pesticides in particular are a major problem.
Large quantities are applied in urban communities to
control vermin, especially in some low-income areas.
For example, the amount of one common insecticide,
chlorpyrifos, applied in one urban borough of
Manhattan in 1997 exceeded the total amount of all
pesticides applied in any other single county in all  of
New York, including in upstate agricultural regions
(Landrigan et al. 1999).  Exposure to pesticides is of
special concern for certain sensitive groups such as
pregnant women, infants, and children.
 Total pounds of pesticide products
 applied by commercial applicators
 and sold to farmers in 1997
 in New York State, by county
   Pounds by county

   D 1,300,000-2.587.057 Ibs.
   D 500,000-1,300,000 Ibs.
   B 120,000-500,000 Ibs.
   D 2,155-120,000 Ibs.

 Source: Adapted from Landriian et a!. 1999
                                                        Prenatal and early postnatal periods are critical
                                                        life stages, and they require careful assessment for
                                                        pesticide exposure. In early life, the nervous system is
                                                        still developing, and it is more susceptible to effects
                                                        from exposure to neurotoxic pesticides. STAR research
                                                        results have significantly increased knowledge
                                                        of prenatal pollutant exposure. For example, one
                                                        significant finding is that exposure to certain
                                                        pesticides can have adverse effects on birth size and
                                                        neurodevelopment (Bradman and Whyatt 2005).

                                                        What contributes to fetal vulnerability?
                                                        Many physiological characteristics of a growing fetus
                                                        make it more likely to suffer a health effect from
                                                        exposure to environmental pollutants. Some metabolic
                                                        activities such as clearance by the kidneys and enzyme
                                                        activity in the liver are immature, and these activities
                                                        often are easily disrupted during development because
                                                        they are highly variable throughout gestation and
                                                        following birth (Landrigan et al. 1999, Cordon et al.
                                                        2005). Greater absorption or retention rates of toxic
                                                        substances, a reduced ability to detoxify chemicals
                                                        and repair damage to DNA, and a higher rate of
                                                        cell proliferation are other factors that contribute to
                                                        a fetus's susceptibility to health risks (Perera et al.
                                                        2005). STAR research results have demonstrated some
                                                        of the effects of fetal vulnerability. For example, in
                                                        one study of a group of minority women and their
                                                        infants, scientists measured women's exposure to

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several pollutants including airborne polyaromatic
hydrocarbons (PAHs) (which were monitored during
pregnancy) and chlorpyrifos (which was measured
from the mother and infant at birth). The results
show that exposure to PAHs and pesticides during
pregnancy impairs fetal growth and development
(Perera et al. 2003). The study results also show that
the developing fetus may be 10 times more susceptible
to DNA damage from before-birth exposure to PAHs
than the mother is (Perera et al. 2004, 2005).
Another study has shown the effect on an infant's
growth from exposure before birth to certain
pesticides. This study enrolled pregnant women at
prenatal clinics in January 1998 and followed them
until January 2004, capturing data from a critical
period when EPA began to phase out residential use
of chlopyrifos in 2001. This study included women
exposed to higher levels of pesticides during the
phase-out period as well as women exposed after
the phase-out period. Infants exposed prenatally to
pesticides before the EPA phase-out of chlorpyrifos
showed significantly reduced birth weight  and shorter
length (Whyatt et al 2004, 2005). Other studies
showed that infants were born with low activity levels
of an enzyme, paraoxonase  1 (PON1), which affects
the metabolism and detoxification of pesticides
(Furlong et al. 2006). Infants with prenatal pesticide
exposure and low PON1 enzyme levels had smaller
head circumferences (Berkowitz et al. 2004, Wolff et
al. 2007).
These results cause concern because  outcomes such as
a smaller head circumference correlate with reduced
intelligence quotient levels and decreased cognitive
function in later years. Study results indicate early-life
exposures are more likely to lead to adverse health
outcomes than similar exposures encountered later
in life. Even more troubling are results that show the
deficits sustained in early life may persist throughout
life (Landrigan et al. 1999). For example, one study
showed that prenatal PAH exposure led to  cognitive
development issues later in life, including  higher risk
for performance deficits in language, reading, and
math in early school years (Perera et al. 2006).
How do we measure exposures relevant to fetal
growth and development?
Measuring exposure to environmental pollutants is
difficult for a number of reasons. Exposure can vary
widely across age groups depending on factors such
as the amount and type of chemical used and daily
patterns of life. Exposure can be of different durations
and magnitudes such as short-term, high-level
pesticide applications versus long-term, low-level
pesticide applications. Some pollutants do not persist
in the body for a long time, making them hard to
measure without frequent sampling (Bradman and
Whyatt 2005, Fenske et al. 2005). Because prenatal
development is so critical, it is particularly important
to assess maternal exposure to environmental
chemicals during pregnancy to make subsequent
associations with infant health (Fenske et al. 2005).
In general, maternal and infant exposures typically
are measured using one or more of the currently
available techniques; scientists take the advantages
and limitations of each method into account
when designing a research study. The techniques
currently used include (Bradman and Whyatt 2005,
Fenske et al. 2005):
  •  Biological monitoring—Uses biomarkers
    (biological substances (blood,  DNA, saliva,
    breast milk,  urine, hair, etc.) to indicate exposure,
    or early biological effect to an environmental
    chemical, or susceptibility to disease)  to provide a
    direct measure of the concentration of a pollutant
    in the body at a given time.
  •  Environmental monitoring—Uses environmental
    samples such as air, dust, diet, and drinking
    water to characterize residential contamination
    and provide  a measure of potential exposure
    to the pollutant.

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  • Survey questionnaire—Uses participant
    surveys to collect general information on a
    person's habits and use of chemicals (typically
    conducted as a supplement to biological and
    environmental monitoring).
  • Ecological methods—Uses geographic
    information systems and other techniques to
    help map the relative locations of populations
    potentially exposed to pollutant sources.
While biological monitoring appears to be one of
the best ways to assess exposure, all biomarkers
have limitations, and certain methods may not truly
represent the full extent of exposure. For example,
pollutants measured in blood represent only a
snapshot of exposure because the body constantly
metabolizes, redistributes, and eliminates chemicals
(Ostrea et al. 2002). Additionally, drawing blood is
invasive, especially when children are involved. Some
scientists (Corrion et al. 2005) are looking for more
innovative techniques that address this problem, such
as sampling maternal and umbilical cord whole blood
rather than blood serum (because pesticides are more
likely to concentrate in red blood cells).  One reason
blood sampling is attractive for biological monitoring
is because, unlike urine, blood is highly  regulated,
and factors such as water intake are less likely to
alter concentrations.
Other studies indicate that meconium, the first set of
stools of a newborn, is a useful biomarker of prenatal
exposure to pollutants such as pesticides. Meconium is
a direct measure of exposure before birth (Ostrea et al.
2006, Whyatt and Barr 2001, Bearer et al. 2005), and
the main advantage over other biological measures is
that it has a wide window of exposure time. Meconium
starts forming at the beginning of the second trimester
and is not excreted until after birth. Although
it provides a cumulative prenatal measurement,
meconium is more difficult to analyze when compared
with blood or urine (Ostrea et al. 2006).
       Neonatal: Genetic Vulnerability
                              1

        r>
Like the developing fetus, neonates (birth to <3
months) are more susceptible to health effects from
pollutant exposure than adults because they are still
developing. Additionally, genetic differences can
increase their vulnerability to pollutants such as
pesticides, secondhand smoke, and air toxics. Genetic
differences may occur either as a difference in a gene
itself or in how the information from a gene is
processed. Genetic differences can significantly affect
metabolism and cause increased susceptibility for
children at all life stages, but the neonatal period is
unique in that newborns display some genetic
characteristics that are different from those observed
for adults or even older children.
An important example of a genetic difference in
neonates involves an enzyme that plays a key role in
protecting humans against toxic effects of pesticides.
Enzymes are proteins that help to accelerate chemical
reactions in the body, and in this case, the enzyme
PON1 facilitates the breakdown of pesticides into a
less toxic form. For several decades, scientists have
shown that high levels of PON 1 are protective against
nervous system effects associated with exposure
to pesticides during development. More recently,
researchers have  demonstrated that having low levels
of PON 1 results in greater sensitivity to these harmful
effects. By knocking out the PON 1 gene in neonatal
mice—an animal model often used as a substitute
for humans—researchers demonstrated an increase
in sensitivity to certain insecticide exposures when
compared with mice that still had the PON1 gene
(Furlong et al. 2005).
In several Children's Center projects, researchers have
shown that the enzyme PON1 is typically not fully
functional until after birth. Even after birth, newborns
and infants have  very low levels of this enzyme. The
results of a review of active PON1 levels in humans
show that the enzyme levels increase from birth
through infancy (Costa et al. 2003). PON1  levels reach
a plateau at different ages in individuals anywhere
from 15 to 25 months, depending on factors such as
the individual's genetic background. Before the levels
plateau, an infant is much more vulnerable to health
effects resulting from exposure to pesticides.

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    "People have this remarkable difference
    in enzymes that defend their health
    from pesticide exposure. In developing
    regulatory standards for safe levels of
    exposure,  we need to protect the most
    sensitive in a population, particularly
    because children and unborn fetuses
    are involved."
       - Dr. Nina Holland,
         L/C Berkeley
Researchers observed variability not only in reaching
the plateau, but also in the range of PON 1 levels
among newborns when compared with their mothers.
Levels of this critical enzyme varied by 26-fold in
newborns compared with only 14-fold among mothers
(Furlong et al. 2006). Even considering the variability
among individuals, average PON1 levels in children
were four times lower than the PON 1 levels in the
mothers, demonstrating that infants clearly are a more
vulnerable population in their ability to detoxify
certain commonly used insecticides (Chen et al. 2003,
Furlong et al. 2006). Researchers confirmed the
observation that PON1 levels are lower in children,
and that the differences between adults and children
vary by ethnicity: The average PON1 level in adults
compared with newborns was 2.6 times higher for
African Americans, 3.6 times greater in the Caribbean
Hispanic population, and 4.6 times greater for
Caucasians (Chen et al. 2003).
 S-
 §.
    160
    120
    80
    40
              Maternal
                                    Neonate
      Average PON1 activity for all genotypes and race/ethnicities
      for mothers and neonates.
      Source: Chen et al. 2003 (Tables 2 and 3); median of all values plotted; error bars
      represent the range in the means for the various genotypes.
In addition to studies that focus on pesticides, some
STAR research studies focus on early exposure to
environmental tobacco smoke (ETS), air toxics, and
other pollutants encountered in the neonatal period.
For example, scientists investigated long-term genetic
effects of prenatal exposure to ETS through maternal
smoking and early life exposures (Gilliland et al. 2001,
2002a, 2002b). The researchers found a candidate
gene that reduces the effects of the exposure to ETS by
detoxifying some of the harmful chemicals associated
with smoking. Because tobacco-related toxins are
more harmful to a developing fetus or infant than
to the mother, the presence of this candidate gene,
glutathione S transferase Ml (GSTM1), may be
especially important during the early life stages. More
specifically, the adverse effects of prenatal exposure
to maternal smoking (e.g., asthma, wheezing) were
predominantly observed in children with a variation of
GSTM1, the null genotype, which lacks the enzyme
that helps to detoxify the pollutants associated with
ETS (Gilliland et al. 2002a). Damage during fetal
development in particular can permanently alter the
structure or function of the lungs, and thus  can lead
to postnatal vulnerabilities (Gilliland et al. 2003). In
addition, large deficits in lung function are  found in
school-aged children with both early-onset asthma and
before-birth exposure to maternal smoking regardless
of whether the child had ETS exposure later in life
(Gilliland et al. 2001, Gilliland et al. 2003,  Li et al.
2005). These results further emphasize the importance
of early exposure and confirm that exposure before
birth to maternal smoking is a critical risk factor for
childhood asthma.
Strikingly, environmental exposures also may change
genetic  susceptibility. Results from  STAR research
show a new association between smoking during
pregnancy and a child's risk of asthma that extends
beyond one generation (Li et al. 2005). These
groundbreaking results show an increased risk of
asthma across multiple generations, meaning that
if a woman smokes during pregnancy, her child's
risk of developing asthma increases, and even if that
child doesn't become a smoker in adulthood, the
next generation (grandchildren) will still have an
increased risk. Potentially, this could occur through
epigenetic mechanisms (interactions between genes
and the  environment that produce differences between
cells during development before birth, but that do
not involve changes to the underlying DNA). The
researchers suggest that tobacco products may affect
both immune function and pollutant detoxification
mechanisms in the offspring by altering DNA patterns
in the fetal  cells (Li et al. 2005). This alteration would
result in an increased genetic susceptibility to asthma
affecting one generation to the next.

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Allergic sensitization and responses to allergies and
chemicals have become the focus of much STAR grant
research, especially for infants/crawlers (3 to <12
months old) whose immune systems are still in the
early stages of development. One reason for this focus
is because asthma is the most common chronic disease
among children. Asthma is an immune system disorder
manifested when the airways  in the lungs strongly
react to various factors, such as stress, allergens,
temperature, exercise, and air pollutants in the air that
generally pose no risk to individuals with healthy
immune systems. In individuals susceptible to asthma,
reaction to these factors can cause the airways to
become irritated and inflamed, and may evoke
symptoms such as wheezing,  coughing, chest
tightness, and difficulty breathing. Although a large
body of evidence has linked life style and
environmental exposures to asthma, the timing of such
environmental exposures during early development
also may be critical to how children become
susceptible to allergens that previously had no effect
(that is,  allergic sensitization), as well as the later
development of asthma.
One way scientists are exploring the relationship
between asthma and age is to measure biomarkers that
indicate this immune system disorder. Researchers
compared levels of type 1 and type 2  T-helper cells
(Thl and Th2) in infants to observe relationships
caused by exposure to pesticides, natural toxins,
and allergens  and compared the data to the resulting
incidence of asthma (Duramad et al. 2006). The
selected infants were subjects of the Center for
Health Assessment of Mothers and Children of
Salinas  (CHAMACOS) birth-cohort study. The study
comprises infants of farm workers in  rural areas.
Infants in this study population may have experienced
greater exposure to pesticides because of their
proximity to fields and contact with pesticide residues
brought home by their parents. Researchers took
blood samples from the infants at 12 and 24 months
to measure the amount of Thl andTh2 cells. The
results indicated that infants who live with agricultural
workers and whose mothers work in the field had
higher levels of Th2 cells than infants who did not
meet these criteria. These are important findings
because 2-year-old children diagnosed with asthma
and wheezing exhibit a significant increase in Th2
levels, which means that elevated levels of these cells
in very young children can perhaps indicate the onset
of respiratory or other immune system disorders.
   Using Biomarkers to Discover
   Asthma in Children
   Biomonitoring is the measurement of a
   substance—or its breakdown product,
   known as a metabolite—in biological
   samples such as blood or urine.
   Researchers measure biomarkers and
   then use the data to assess the presence
   of a pollutant such as a pesticide or a
   condition such as asthma.  Because the
   balance between Thl and  Th2 cells is
   important in the development of asthma,
   scientists have examined the levels
   of these cells in blood as a possible
   indicator of asthma in children.  These
   cells are part of the immune system
   and belong to a group of cells essential
   to controlling viruses and bacteria. Thl
   cells tend to provide general protective
   immunity; Th2 cells may play an
   important role in the functional changes
   of allergic diseases, including asthma.
Animal studies also have concentrated on the
importance of age and early immune system
development, allergic sensitization, and allergic and
chemical response. One such study focused on the

-------
relationship between age and the onset of allergies in
mice (Rumold et al. 2001). Investigators for this study
examined the effect of age on the response to
environmental ETS and its possible role in
sensitization to normally harmless  substances.
Studying how ETS affects infants and crawlers is very
important because secondhand smoke exposure causes
numerous problems in children, such as slower lung
growth, acute respiratory infections, ear problems, and
more frequent and severe asthma attacks. In the study,
young mice aged 2 to 3 weeks and  adult mice aged 6
to 8 weeks received exposure to (1) ETS, (2) a protein
called ovalbumin (OVA) that stimulates an immune
response but that is typically harmless, or (3) both ETS
and OVA. Investigators measured the animal's ability
to respond and defend itself based on levels  of two
immunoglobulins (Ig), IgE and IgGl. IgE is an
antibody class that plays a role in allergic responses; it
binds to allergens and triggers the release of
histamines (important substances involved in many
allergic reactions). IgGl is a subclass of IgG, which
provides the majority of antibody-based immunity
against invading pathogens.  Researchers detected the
antibodies in both adult and young  mice exposed to
both ETS and OVA. Because exposure to ETS and
OVA together created an allergic response, but not
OVA or ETS exposure alone, results suggest that ETS
can create allergic sensitization to otherwise harmless
substances. Furthermore, the young mice had
significantly higher antibody levels, which may explain
why exposure to secondhand smoke is a major risk
factor for the development of allergies in
young children.
        CENTER roil THt HEALTH ASSESSMENT Of
        MOTHERS AND CHILDREN OF SALINAS
        http://ehs.sph.berkeley.edu/chamacos
What is an antibody?
An antibody is a protein whose
primary responsibility is defending the
body as part of the immune system.
In response to bacteria or viruses,
mature B cells or plasma cells, make
antibodies. In mammals, there are
five classes of antibodies.  Each class
is named with an "Ig" prefix,  which
stands for immunoglobulin -  another
name for an antibody. These  antibody
classes - IgA, IgD,  IgE,  IgG and
IgM - differ in their biologic properties,
their function, where they are found in
the body, and their ability to interact
with various substances that stimulate
antibody production.
                 Bcell
                                                              Plasma cell
                                                                                     Antibody

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Children are often exposed to contaminants at levels
that are equal to, or greater than, adult levels of
exposure (Black et al. 2005; Harnley et al. 2005).
Relative to their body weight, children typically eat
more food, drink more water, and breathe in more air
than adults, and because they are less able than adults
to rid their bodies  of contaminants or reduce the
toxicity of pollutants, the effects in children associated
with these exposures can be greater (Eskenazi et al.
1999; Bearer 2000). Children also may have a greater
level of exposure to contaminants because they tend to
put items in their mouth, they are closer to potentially
contaminated floors and surfaces, and they spend more
time inside the home.
By spending a significant portion of their time
inside, children are exposed to a complex mix of
contaminants including pesticides that come from
numerous sources such as outdoor air, tracked-in
particles, and various indoor sources that can vary in
nature by geographic region (Lioy 2006; Akland et
al. 2000). For example, researchers have measured
pesticide contamination levels in the homes of families
living close to agricultural activities (Freeman et al.
2004; Shalat et al. 2003; Eskenazi et al. 1999). In one
agricultural community, children had 3.5 to 13 times
higher urinary pesticide metabolites than children
in the National Health and Nutrition Examination
Survey (NHANES) database, a database containing
information on the health and nutritional status of
adults and children in the United States (Shalat et al.
2003). This exposure to pesticides from agricultural
application is a concern for children living in homes
adjacent to or in close proximity of agricultural fields
and orchards (Ramaprasad et al. 2004).
In addition to the amount of time spent indoors,
children's other activities also greatly influence their
potential exposure to environmental contaminants
(Black et al. 2005). The frequency, duration, and
nature of a child's interaction with contaminated media
determine the degree of a child's exposure. Young
children, through a number of normal activities and
behaviors, have the potential to sustain substantial
exposure to contaminants such as pesticides. For
example, studies demonstrate that toddlers (children
ages 12 months to <2 years) have higher levels of
pesticides on their clothing, as well as higher
concentrations of urinary metabolites, when compared
with younger infants (Bradman et al. 2007). Toddlers
are extremely susceptible to pesticide exposure in the
indoor environment because of their characteristic
behaviors. At the toddler stage, children consume a
full range of foods because breast- and bottle-feeding
cease. They participate in increased play activities, are
extremely curious, and exercise poor judgment.
Toddlers walk upright, run, climb, occupy a wider
variety of breathing zones, and engage in more
vigorous activities than younger infants do
(EPA 2005).
    "Pesticide exposure isn't a great idea for
    adults, but it poses a particular concern
    in regards to children. These smallest
    humans,  who spend a lot of time close
    to the floor and with their hands in their
    mouths, can encounter much higher
    doses relative to their body weights."
      — Phi/lips 2005

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Furthermore, toddlers have several microactivities
that help determine their level of exposure. Toddlers
frequently insert objects or hands into their mouths;
demonstrate poor food handling skills; and use objects
such as toys, bottles, pacifiers, and blankets in the
home that may affect exposure (Black et al. 2005;
Freeman et al. 200la; Akland et al. 2000). The activity
of eating and food contamination is a specific concern
(and this finding extends to children 3 years of age
as well as toddlers). In fact, research results suggest
that poor food handling skills can increase a child's
potential for exposure from hand-to-food, food-to-
surface, and hand-to-surface  contacts to pesticides
(Akland et al. 2000). Children spend a significant
portion of their waking hours engaged in eating and
other activities during which  their hands are exposed
to contaminated surfaces. For example, Freeman  et al.
(2001b) reported that 63 percent of toddlers ate food
that had been on the floor.
While researchers have evaluated some microactivities,
much remains unknown. Identifying the link between
a child's behavior and the resulting amount of a
contaminant that enters a child's body is an extremely
important step in determining the significance of
an exposure (Black et al. 2005). A number of novel
methods have helped determine the link between
behavior and dose. One new approach developed
at the University of Washington Center for Child
Environmental Health Risks Research involves the
use of global positioning system technology for
characterizing children's activity patterns  (EPA 2007a).
Another novel method involves the use of laser-based,
real-time measurement of pesticide spray drift, a
frequent occurrence in agricultural communities.
   Why the potential for food
   contamination while eating is a
   specific concern for children:
   • Approximately 20 to 80 percent of a
      child's dietary exposure results from
      handling his or her food.
   • A child's hands contact contaminated
      surfaces up to 32 times during eating.
   • A child's contaminated hands then contact
      his or her food 10 to 39 times before it
      enters his or her mouth during eating.
   Source: Akland et al. 2000.
This tracking technique will help in estimating
community residents' and bystanders' exposure to
pesticide drift (EPA 2007a; Tsai et al. 2005). A third
new approach uses videotaping to capture behaviors
and detail needed to quantify exposures. (See text box
on page 16.)
As concerns regarding environmental contaminants
and their effects on children's health continue to
increase, the need continues for more knowledge about
how children's activities influence their exposure.
This knowledge will help in the development of
improved risk assessment models, which subsequently
will promote our understanding of the risks
environmental contaminants pose to children's health.
In turn, policymakers will have more information
when designing strategies to reduce exposure to
contaminants and developing methods to protect
children's health. If communicated effectively, this
increased knowledge will help members of the public
protect themselves and their children from pollutant
exposures.
Path traveled by one child (6-hour sampling time) on a
weekday during school hours.

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The number of preschoolers diagnosed with
neurodevelopmental disorders such as autism, ASD,
Pervasive Developmental Disorder (FDD), and ADHD
has been increasing recently. In California alone, a
210-percent increase in the number of diagnosed cases
of profound autism in children has been recorded in
the past 10 years. Centers for Disease Control and
Prevention (CDC) data released in 2007 show a high
number of cases of ASD in several particular areas in
the United States—approximately 1 in  150 children in
those areas are diagnosed with an ASD by the time they
are 8 years old.
This sudden rise in the number of children exhibiting
neurodevelopmental disorders is worrisome because
scientists have little understanding of the causes and
contributing environmental factors. The preschooler
group, 2 to <6 years of age, is of particular
significance because the symptoms associated
with ASD generally begin before 3 years of age.
Consequently, the scientific community is examining
numerous factors such as environmental influences to
find an explanation for the increasing trend in this age
group (CDC 2007).
One environmental influence under study by
researchers is early exposure to pesticides, an
area that may reveal important information about
neurodevelopmental disorders in children. For
example, researchers are exploring the relationship
between chlorpyrifos (a pesticide used in homes to
kill cockroaches until 2001 when it was banned from
residential sales) and neurodevelopmental disorders
in preschool children through 3 years of age (Rauh et
al. 2006). The investigators are finding that children
who were exposed to high levels of chlorpyrifos before
birth have greater developmental delays in motor
and mental skills when compared with children who
received low exposures. Researchers assess motor
skills by examining endpoints like crawling, walking,
reaching, and grasping; and cognitive  development by
studying how a child perceives, thinks, and gains an
understanding of the world. By 3 years of age, children
with high exposure to pesticides before birth were 11
times more likely to have attention problems, 6.5 times
more likely to have ADHD diagnosis, and 5 times more
Videotaping: A Tool Capable of
Capturing Children's Microactivities
(Freeman et al. 2001a)
Children's microactivities are not well
documented, and understanding how
exposures occur requires recording
how children behave during specific
activities. Detailed information about
microactivities is difficult to obtain
from questionnaires because many
microactivities are behaviors that
caretakers barely notice and cannot
recall. A potential solution is to get
information on microactivities from
direct or videotaped observations.
For example, during the Minnesota
Children's Pesticide Exposure Study
(MNCPES)—a population-based study
in the National Human Exposure
Assessment Survey—researchers
videotaped 19 of the 102 children  for
four consecutive hours of normal daily
activities. The purpose of the MNCPES
was to characterize children's exposure
to residential pesticides and evaluate
the contribution  of children's activities to
their exposures.
Observational data  from MNCPES
expanded the existing microactivity
database of observational studies,
including the knowledge that most of
children's frequent  contacts with the
environment are short (typically less
than 5 seconds in duration). Although
the MNCPES observed children
older than 3 years,  the videotaping
method is applicable for children of all
ages.  Improved understanding of the
variability of microactivities will help
protect the most vulnerable children.

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likely to have FDD diagnosis than children with low
exposure. These results show that not only is there an
association between prenatal exposures to high levels
of pesticides and neurodevelopmental delays, but also
that symptoms of these delays begin to present
strongly during preschool years.
   Types of Neurodevelopmental
   Disorders
   Autism—A developmental disability that
   results from a disorder of the human
   central nervous system. It is diagnosed
   using specific criteria for impairments
   to social interaction, communication,
   interests, imagination, and activities.
   Autism Spectrum Disorder—
   A developmental and behavioral
   syndrome that results from certain
   combinations of characteristically
   autistic traits.
   Pervasive Developmental
   Disorder—A group of five disorders
   (Autistic Disorder, Rett's Disorder,
   Childhood Disintegrative  Disorder,
   Asperger's Syndrome, and Pervasive
   Developmental Disorder Not Otherwise
   Specified) characterized  by delays
   in development.
   Attention Deficit Hyperactivity
   Disorder—A largely neurological
   developmental disorder characterized
   by a persistent pattern of inattention or
   hyperactivity-impulsivity,  or both.
              t

         http://beincharge.ucdavis.edu/
To better understand autism and its underlying causes,
investigators at UC Davis are conducting a large-scale
study called CHARGE (Childhood Autism Risks from
Genetics and the Environment), examining potential
genetic and environmental causes and triggers of
autism (Hertz-Picciotto et al. 2006). The CHARGE
investigators are particularly interested in studying the
role the immune system plays in autism. The study
enrolled children 2 to 5 years of age in Northern
California diagnosed with autism. One of the key
findings of this study showed higher levels of the
hormone leptin in  their blood (Ashwood et al. 2007).
Leptin, a hormone known for its important effects on
regulating body weight, metabolism, and reproductive
function, also influences the immune system. When
the body has too little of this hormone, the immune
system is less responsive. Researchers identified
children in the study who were diagnosed with early
onset autism and regressive autism. Early onset autism
refers to children with early delays in the development
of language or social skills, or both; regressive autism
refers to children who develop  some  language or social
skills, or both, but who, between the ages of 18 to 24
months, lose those skills. Children diagnosed with
early onset autism had significantly higher blood levels
of leptin as compared with children diagnosed with
regressive autism.  This finding is important because
leptin may be the first biomarker to distinguish
children with early onset autism from children with
regressive autism.  Because of its role in the immune
system, leptin also may be an important biomarker of
susceptibility to environmental triggers such as
pollutants  and pesticides.
Because the early interplay between toxic exposures,
immune function, and neurological development appear
to be strongly linked, the CHARGE investigators are
evaluating blood samples from autistic children for
other biomarkers of the immune system. Investigators
found that children with autism have significantly
lower levels of certain antibodies, show a significantly
decreased response to some vaccinations for prevention
of bacterial diseases, and have significantly increased
levels of certain proteins that help amplify inflammatory
reactions (EPA Grant Number R829388C002). The
blood samples also show that autistic children have
higher levels of natural killer cells and CDS cells,
which play similar roles in the immune system (EPA
Grant Number R829388C003).  Both cell types attack
and destroy many foreign cells—natural killer cells kill
right away; CDS cells are more specific and follow a
process before attacking and killing the foreign cell.
The observed  different levels of antibodies and cells in
the immune systems of autistic children are significant
because they indicate that autism may be linked to
environmental triggers affecting the immune system.

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            Environmental Exposures
         Assessed in the CHARGE Study
  Organic pollutants
  (PCBs, PBDEs, phthalates)
  Medical procedures
  & Pharmaceuticals
 Biospecimens:
   Blood
   Hair (past exposures)
 -»Baby lock (first year of life)
   Mother's hair (if long enough, prenatal)
   Urine
   Buccal cells
 Interviews:
   Diet
   Residential information
   Lifestyle
   Consumer products
--» Medical history
 Linkage to exposure databases
   Air pollution, water contamination,
   pesticide use, hazardous waste sites
••Medical records
Asthma is the most common chronic disease of
childhood in the developed world. In the United States,
pediatric asthma affects approximately five million
children under the age of 18 (Keeler et al. 2002).
Furthermore, the prevalence rate of pediatric asthma
(under 18 years of age) in the United States increased by
61 percent from 1982 to 1994 (Keeler et al. 2002), and
the mortality rate from pediatric asthma increased by 78
percent from 1980 to 1993 (Keeler et al.  2002; Clark et
al. 1999). Children in urban areas, especially poor and
minority children, represent a sensitive subpopulation
because they spend a significant portion of their time
indoors where irritating and allergenic substances are
prevalent. This indoor exposure to allergens may
increase a child's susceptibility to allergic sensitization,
respiratory symptoms, and ultimately the development
of asthma (Limb et al. 2005; Perera et al. 2002). While
the consequences for the current U.S. population
afflicted with pediatric asthma are unknown, large
deficits in lung function persist into adulthood. The
extent of the deficits associated with asthma is greater
than it is with smoking (Berhane et al. 2000).
                                       Children and Asthma Video
"Each year, asthma kills more than 600
American children, and since 1980 the
incidence of the disease has doubled
and now affects over 5 million children
in the U.S. Low-income children living
in urban areas are at highest risk,  but
the disease cuts across socioeconomic
and geographic boundaries."
View the video:
http://www.epa.gov/ncer/childrenscenters/
multimedia.html#child  asthma
                                    Research results indicate that in addition to genetic
                                    disposition, demographic variables, and psychosocial
                                    stressors, indoor environmental exposures may
                                    contribute significantly to the worldwide increase
                                    of asthma (Eggleston et al. 2005; Keeler et al.
                                    2002; Rauh et al. 2002). In fact, 80 to 90 percent of
                                    asthmatic children become sensitized to airborne
                                    environmental allergens beginning at school age (6
                                    years of age and less than 11 years of age) (Zeldin et
                                    al. 2006). Some of the strongest associations between
                                    asthma and indoor allergen exposure have been found
                                    with dust mites, rodents, pets, and cockroaches (Zeldin
                                    et al. 2006; Kinney et al. 2002; Rauh et al. 2002).
                                    Exposure to ETS during childhood also appears to play
                                    an important role in asthma causation and aggravation
                                    (Zeldin et al. 2006).

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    Air Currents
     Source
While investigators have identified environmental
allergens as a potential cause for childhood asthma,
the actual concentration of allergens that a child
is exposed to remains uncertain (Zeldin et al.
2006). "Exposure dose" is dependent on both the
  concentration inhaled and the duration of exposure
  (Eggleston 2005). The most effective method of
  reducing exposure dose is to remove the source of the
  contaminant (Eggleston 2005). To achieve adequate
  source removal, it is necessary to conduct further
  research to better understand and address the sources
  of indoor and outdoor pollutants (Keeler et al. 2002).
  Research in this area is making progress. For example,
  studies have demonstrated that more than three-
  quarters of U.S. homes have detectable concentrations
  of mouse allergen. Although mouse allergen is
  almost ubiquitous in inner-city homes and occurs in
  approximately 75 percent of middle-class suburban
  homes, analyses of settled dust concentrations of
  mouse allergen indicate that indoor levels are 10-fold
  higher in inner-city homes than suburban homes
  (Matsui et al. 2005). Studies have suggested that the
  distribution of cockroach allergen is dependent on the
  built environment and that cockroach allergen persists
  for months after successful pest control (Eggleston
  2005; Eggleston 2003). While it is impossible to make
  indoor environments allergen free, proven effective
  intervention methods for reducing most indoor
  allergens have been developed based on this increasing
  knowledge base (table 4). It is important to recognize
  that each intervention method requires a somewhat
  different approach.
Table 4. Allergen Characteristics and Possible Exposure-Reduction Methods
               Allergen Characteristics
           Exposure-Reduction Methods
  Dust Mite
  • Carried on relatively large particles (10 to 30
    micrometers) that do not remain airborne for long
  • Infestation on fabrics, especially bedding
• Fitting allergen-proof encasings to the mattress and
  pillow
• Vacuuming, cleaning, and washing all bedding
  regularly
• Relocating the bedroom
• Applying pesticides designed to kill mites
• Dehumidifying
• Removing wall-to-wall carpeting
  Pet
   1 Carried on small particles that remain airborne and
    are extremely adherent to surfaces and clothing
• Using air filters
• Removing pet
• Removing carpets, furniture, and other reservoirs
• Purchasing new bedding

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               Allergen Characteristics
          Exposure-Reduction Methods
  Rodent
  • Carried on particles that are small and remain
    airborne
  • Widely distributed and commonly found in homes
    that are not infested with mice
• Applying Integrated Pest Management (IPM) to
  reduce exposures by combining nonchemical
  approaches, education, and information on the
  life cycles of pests and their interactions with the
  environment
• Removing basic rodent survival elements such as air,
  moisture, food, and shelter by sealing cracks and
  crevices
• Carefully placing least-toxic baits and gels
• Maintaining properties
• Sanitizing properties to remove the allergen
• Educating residents
• Specially training professionals to conduct
  interventions
  Cockroach
  • Resembles mite allergens with up to 80 percent of
    aeroallergens carried on  larger particles (>10 mi-
    crometers) that are detectable mainly after vigorous
    activity and settle rapidly
  • Highly mobile; therefore, spreads widely throughout
    the home, especially in bedding and kitchens
  • Concentrates behind appliances and in cracks and
    crevices
• Using IPM
• Cleaning to remove food sources, grease, food debris
• Storing food in plastic containers kept in a
  refrigerator
  Environmental Tobacco Smoke
  • Widespread exposure—approximately 15 million
    children in the United States are exposed to
    environmental tobacco smoke (ETS)
  • Restricts lung growth and development, which
    results in reduced pulmonary function
• Removing sources of cigarette smoke from the
  indoor environment
Sources: Apter and Eggleston 2005; Brenner et al. 2003; Clark 1999; Eggleston 2005; Gilliland et al. 2000; Matsui et al.
2005; Phipatanakul et al. 2004
While these personal-level interventions are helpful,
researchers recognize that to successfully combat
the rising pediatric asthma prevalence rate, more
community-based participatory approaches to
interventions are needed. Urban environments are
complex; they consist of a network of factors that
potentially contribute to environmental allergens.
Urban areas often contain multifamily residences,
a high density of grocery stores and restaurants,
substandard housing maintenance, and an inadequate
sanitation infrastructure. All of these factors
potentially could increase the prevalence and
concentrations of environmental allergens; therefore,
it is important to target asthma interventions at the
community level (Chew et al. 2003). Researchers
are beginning to recognize the value of including the
  intended beneficiaries in the planning, implementation,
  and evaluation of research (Parker et al. 2003; Clark et
  al. 1999). Involving community partners in collecting,
  analyzing, interpreting, and disseminating the research
  results, as well as developing, implementing, and
  evaluating household-, community-, and policy-level
  strategies aimed at reducing exposures and improving
  children's health, will help make interventions
  successful (Keeler et al. 2002; Clark et al. 1999).
  Several CBPR projects (some completed, some in
  progress) have actively involved community members
  in the research. The following projects investigated
  multiple exposures and susceptibility factors that may
  disproportionately affect children and the interactions
  between community members:

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• Community Action Against Asthma (CAAA):
The overall goal of this CBPR project is to better
understand environmental triggers and psychosocial
factors such as family tensions, physical activity,
anxiety and stress, and friends and peer pressure
on children with asthma. Understanding this
cause-and-effect relationship will help reduce
various asthma triggers through household- and
neighborhood-level interventions. Specifically, the
CAAA study conducts research on the effects of
environmental exposures on the residents of Detroit,
Michigan, through a CBPR process. Participants
and researchers are involved in all aspects of the
design and conduct of research, and all parties
involved receive the study results. The study uses the
research to design, in collaboration with all partners,
interventions to reduce identified environmental
exposures (Keeler et al. 2002).
• Inner-City Asthma Study: The overall goal of
this project was to design intervention strategies to
reduce allergen and paniculate exposures. Results
show that airborne particulates and allergens
affect asthma synergistically. The intervention
involved the following approaches: home-based
education, cockroach and rodent extermination,
mattress and pillow encasings, and cleaning with
high-efficiency particulate air (HEPA) filters. The
research results indicate that an intervention that
combines strategies to reduce indoor pollutants
and allergens simultaneously with education of
residents in inner-city homes substantially reduces
exposure levels of particulate matter and allergens.
The research results also indicate modest reductions
of symptoms in asthmatic children who live in
homes treated with this combination intervention
(Eggleston et al. 2005).
• National Cooperative Inner-City Asthma Study:
This study consisted of a family-focused asthma
intervention for low-income, inner-city children
with moderate to severe asthma and their family
members. The research focused on both problem
solving and asthma education so that participants
would have an improved understanding of the
disease and gain the skills to avoid asthma
triggers. The study demonstrated how common
environmental allergens are in inner-city homes
and how strongly sensitization and asthma
morbidity relate to exposure. The current preferred
approach is using IPM combined with pesticide
application, accompanied with family education and
maintenance of the built environment (Chew et al.
2003; Eggleston 2003; Rauh et al. 2002).
• Integrated Pest Management Study in  East
Harlem, New York City: This study was a two-
pronged prevention and intervention program to
test whether IPM techniques in combination with
  education targeted at the household level could
  reduce cockroach allergens and decrease reliance
  on chemical pesticides in the urban home. Although
  the study demonstrated that IPM techniques are
  effective and relatively economical, success depends
  on direct involvement of the community residents
  in the development and implementation phases and
  education and guidance from pest control experts.
  Building managers, superintendents, and others
  who provide services to urban residences also must
  support the IPM efforts (Brenner et al. 2003).
    Columbia University Center for Children's
    Environmental Health has been honored
    with an Excellence Award from the EPA
    Office of Children's Health Protection
    for its Integrated Pest Management
    interventions. This program trains and
    educates tenants to use IPM practices,
    which include reducing the levels of toxic
    pesticide use inside their homes and
    sealing cracks and crevices, as well as
    reducing asthma-triggering pet allergens.
Although researchers have made progress in
establishing the causes of the rising rate of pediatric
asthma, the need continues for a better definition of
susceptible populations and a better understanding
of the effect of allergens on susceptible individuals.
Protecting children's health will require identifying
preventable risks and rapidly translating this
knowledge into protective policies and interventions
(Perera et al. 2002). Continued CBPR will give
researchers and policymakers a better understanding
of the interactions between multiple exposures and
susceptibility factors that disproportionately affect
certain populations (Perera et al. 2002), and CBPR
can help make policymakers aware of susceptible
populations when they formulate new standards and
policies (Lewis  et al. 2005; Clark et al. 1999). For
example, researchers using CBPR could address the
fact that asthma is especially prevalent in urban and
minority populations (Keeler et al. 2002; Kinney
et al. 2002; Clark et al. 1999). Researchers and
policymakers using CBPR could develop effective and
sustainable strategies  for communities with susceptible
populations such as disproportionately high levels of
exposure to ETS and allergens and people who lack
access to medical care, financial resources, and social
support to effectively  manage the disease long-term
(Clark etal. 1999).

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Children's  Health  and  The  Environment:
Emerging Trends,  Current Work,  And  Future  Directions
Over the past fifty years, the trends in health threats
to the Nation's children have changed significantly.
By creating safer drinking water and healthier
environments, we have made tremendous progress
in reducing childhood infectious diseases and infant
mortality. Science-based policies have brought public
health successes in certain areas of environmental
health. For example, lead exposure prevention
programs have reduced the average blood lead levels
of children in the United States. Additionally, advances
in asthma research have enabled pediatricians to
detect the warning signs of respiratory distress
earlier and to intervene through environmental and
clinical management. Today, scientists now face
increasingly complex questions and must deal with
chronic health challenges affecting children, including
impairments in growth and development, increased
rates of preterm birth and low birth weight (LBW)
babies, childhood obesity, Type 2 diabetes, and poorly
understood developmental disabilities such as autism.
Identifying the potential role of the environment in the
development or progression of these diseases is further
complicated by the emergence of many new chemicals
in both domestic  and international markets that are
increasingly ubiquitous at low levels.
As discussed in this report, STAR research is starting
to address these more complex questions. For example,
EPA-funded researchers are providing cutting edge
epidemiology and basic science insights to answer
questions about:
  •  LBW and Preterm Birth: LBW babies and
  babies born before term (preterm birth) are at
  increased risk for various health problems (Stevens
  et al. 2002). Despite overall improvements in
  prenatal care in the United States, rates of LBW
  and preterm births continue to rise (Hamilton,
  et al 2006). STAR researchers have published
  scientific findings on the association between certain
  environmental  exposures (e.g. organophosphate
  pesticides and air pollution) in the womb and
  increased risk of preterm birth and low birth weight
  babies. Furthermore, in 2007, EPA launched a new
  Children's Center at Duke University that seeks to
  understand the disparities in adverse birth outcomes,
  particularly in the American South as they relate
  to environmental exposures, complex genetic
  interactions, and community-level influences.
  •  Childhood Obesity: Rates of childhood obesity
  in America are increasing; an estimated 17 percent
  of children and adolescents aged 12-19 years are
  overweight (CDC 2007). Obesity is a complex issue
  related to lifestyle, environment, and genes. Recent
  data have shown that there are plausible biological
  mechanisms through which chemical exposures
  can disrupt hormonal processes. STAR research is
  investigating the links between early life exposures
  to endocrine disrupting chemicals and childhood
  obesity, early pubescent development, and Type 2
  diabetes.
  •  Autism Spectrum Disorder: Once reported to
  have an incidence rate in the single digits per 1000,
  ASD today affects one out of every 150 children
  (Rice 2007). Researchers are at the starting point
  in understanding how genetics, environmental
  exposures, maternal infections, and other factors
  can impact child neurodevelopment. For example,
  the summer of 2007 marked the initiation of the
  EPA/NIEHS supported Markers of Autism Risks in
  Babies—Learning the Early Signs (MARBLES)
  study. The lead investigators of MARBLES will
  monitor the environmental and genetic influences
  on pregnancies at higher risk of autistic outcomes
  (http://marbles.ucdavis.edu/).
   "In the South, there is a unique social,
   economic, and demographic context
   in which environmental exposures play
   out. Poor birth outcomes aren't just an
   immediate problem - the effects can be
   very long lasting. Survivors of poor birth
   outcomes are at increased risk for serious
   illnesses later in life."
       - Dr. Marie Lynn Miranda, Duke
        University Children's Center Director
As the science from the past ten years is reviewed, it
is clear that EPA-funded research has led to important
advances in understanding how environmental factors
affect children's health. This robust body of work
has also informed policies that protect public health.
As EPA looks to the future, however, it is equally
clear that important work remains to be done. EPA,

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along with several other Federal Agencies, will begin
working together to answer some of these more
complex questions through a landmark study - the
National Children's Study - that will examine the
effects of environmental influences on the health and
development of more than 100,000 children across the
United States, following them from before birth until
age 21. This study defines the term "environment"
broadly by considering natural and man-made
environmental factors, biological and chemical factors,
physical surroundings,  social factors, behavioral
influences and outcomes, genetics, cultural influences,
and geographic locations. The NCS will be one of the
richest information resources available for answering
questions related to children's health and development
and will form the basis of child health guidance,
interventions, and policy for generations to come.
       THE  NATIONAL

     CHILDREN'S
                                 STUDY
       HEALTH  GROWTH  ENVIRONMENT

      http://www.nationalchildrensstudy.gov
While EPA-funded research will provide some of
the foundation for this major landmark study by
advancing the science and creating the tools needed
for conducting longitudinal epidemiology studies,
NCER's STAR program will also continue to work
in major emerging areas of scientific inquiry such as
advanced methods for interpreting biomonitoring data
and community-based risk assessment.

Interpreting Human Biomonitoring
Information
Human biomonitoring data is collected as a way of
assessing exposure,  susceptibility, and effects by
researchers involved in  many types of environmental
health studies, including long term studies of the
association between human exposure to environmental
chemicals and resulting health effects. Advances in
measurement technology have made biomonitoring
more popular as a way to track health and monitor
trends in exposure or disease. There are efforts at
the Federal and State levels to collect information
on human exposure to environmental chemicals and
also to use biomonitoring data to assess the public
health impacts of policy decisions. There are still
data gaps, however, in our understanding of what
certain biomarkers actually mean in terms of exposure
and dose. STAR research is starting to fill some of
these knowledge gaps through a program designed
to develop methods and models to  interpret and
understand biomonitoring data. Using sophisticated,
state-of-the-science modeling techniques, STAR
researchers are making headway into this important
area of science. These results will be informative
for scientists and policy makers who rely on
biomonitoring data - including those researchers
working in children's environmental health. A better
understanding of biomarker data will help us more
accurately assess a child's exposure and risk and
can eventually contribute to broader knowledge of
children's environmental health. This program will
help answer questions like what exposure must have
occurred to create the measured biomonitoring level
and, based on the measured biomonitoring level, how
much of this chemical reached a point in the body
where it could potentially do harm.

Community-Based Risk Approaches:
Exploring  Interactions  between Chemical
and Nonchemical Stressors
An important emerging area of environmental
health science is investigating how chemical and
nonchemical stressors - in combination - can impact
health outcomes. NCER is leading  an effort to explore
the opportunities and challenges of this question in
greater detail by initiating a program on conducting
risk assessments that take into account both chemical
and nonchemical stressors in a community and
the potential  health impact of those stressors when
combined. It is likely that STAR research will fill an
important role in this emerging area. It is anticipated
that specific research needs will be identified in
the areas of:  (1) methods to measure chemical and
nonchemical stressors,  susceptibility factors, and
health outcomes at the community  level; (2) the
physiological impacts on nonchemical stressors
and the impact on health outcomes associated with
environmental chemical exposures; and (3) statistical
methods for assessing community and cumulative risk.
The ability to conduct community-level risk
assessments that account for the  many chemical and
nonchemical stressors faced by the population relies
on the use of well-developed tools and methods to
accurately understand exposures to all stressors, the
interactions between stressors, the biological impacts

-------
of those stressors, and the best way to combine and
analyze the information in a way that is useful for risk
assessors and managers. This type of assessment will
move the science of risk assessment and environmental
health forward.

Epilogue
Ten years ago, scientists were just beginning to
answer pressing health and policy questions such
as: How do children's behaviors impact exposure to
environmental toxins? How do children's behaviors
and exposures change over time? Can we identify
biological susceptibilities that increase risk of health
effects in children? Do exposures in the womb
lead to health effects  in children, and if so, to what
extent? Are there effective ways to reduce children's
exposures to environmental chemicals? Can these
effective interventions actually improve children's
health outcomes?
During the past ten years, with the emergence of
biological monitoring, advanced exposure methods,
and the rapidly proliferating science  of human DNA
analysis, STAR-supported researchers and community
partners began answering these questions. Moreover,
many scientists participated directly or indirectly
in creating more protective policies based on sound
science for children at the state and local levels.
Yet many of our most daunting challenges in
children's health protection may lie ahead. In the
future, increasingly complex questions are likely to
arise as the trends in low dose chronic exposures to
multiple new chemicals continue across life stages.
Additionally, global warming, nanotechnology, and
urbanization each present potential risks for children's
health. Yet they also present an opportunity to design
safer, more sustainable environments.
NCER's STAR program will continue to build upon
the successes of the past ten years by supporting the
scientific leaders of tomorrow. Together with our
federal, academic, and community partners, EPA
will step boldly toward answering the questions that
will help create a cleaner environment and healthier
communities for the Nation's children.

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                                Links to  Additional  Information
For more information on the Children's Centers
and NCER's STAR grant program, see the links
below. Other important sources for children's health
information are also provided.
EPA. Children's Centers. Available online at http://
www.epa.gov/ncer/childrenscenters/ or http://
www.niehs.nih.gov/research/supported/centers/
prevention/.
  The Children's Centers are funded jointly
  by EPA's STAR grants, NIEHS, and CDC to
  conduct laboratory, clinical, and behavior
  studies on the environmental factors influencing
  children's health.
EPA. NCER. Available online at
http://www.epa.gov/ncer/.
  NCER supports scientific  research across the
  country on a wide variety  of environmental issues.
  Researchers use these results to develop  and
  support national environmental policies and
  goals. The NCER STAR grant program partially
  funds the Children's Centers and provides other
  grants to focus on children's health.
CDC. Pediatric Environmental Health Specialty
Units (PEHSUs). Available  online at http://www.
atsdr.cdc.gov/HEC/natorg/pehsu.html.
  Funded by the Agency for Toxic Substances and
  Disease Registry (ATSDR) and EPA, PEHSUs
  consist of representatives from pediatric and
  environmental clinics who provide education and
  consultation to health professionals in the field
  of children's environmental health. Currently,
  13 PEHSUs are in operation across the United
  States,  Canada, and Mexico.
Children's Environmental Health Network (CEHN).
Available online at http://www.cehn.org/.
  CEHN is a nonprofit organization that, among
  other endeavors, promotes research in the
  field of  children's health. CEHN stimulates
  research in five priority research areas: asthma
  and respiratory diseases,  childhood cancer,
  neurodevelopmental effects, endocrine and
  sexual disorders, and cross-cutting issues.
EPA. Office of Children's Health Protection
(OCHP). Available online at http://yosemite.epa.
gov/ochp/ochpweb.nsf/content/homepage.htm.
  OCHP works with other EPA Offices and other
  Federal Agencies to promote scientific research
  in children's environmental health, including the
  Toxicity and Exposure Assessment for Children's
  Health (TEACH) program and the National
  Children's Study.
EPA. TEACH. Available online at http://www.epa.
gov/teach/.
  The TEACH Web site and database include
  information on scientific research and Federal
  regulations relating to children's environmental
  health. Currently, TEACH provides nonbiased
  information from numerous sources on 18
  chemicals of concern.
EPA. Voluntary Children's Chemical Evaluation
Program (VCCEP). Available online at
http://www.epa.gov/oppt/vccep/.
  VCCEP was developed in response to the
  Chemical Right-to-Know Initiative, and compiles
  information from companies that manufacture
  and import products that contain one or more of
  the 23 chemicals identified as risks to children.
National Institutes of Health (NIH). National
Children's Study. Available online at
http://www.nationalchildrensstudy.gov/.
  Beginning this year, the National Children's Study
  will track the physical  and mental health of more
  than 100,000 children from before birth until age
  21 in an effort to determine the environmental
  factors that affect children's health.
World Health Organization (WHO). Child and
Adolescent  Health and Development (CAH).
Available online at
http://www.who.int/child-adolescent-health/.
  CAH gathers data on children from birth
  through 19 years of age, focusing on the burden
  of disease and the effectiveness of public
  health interventions

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&EPA
     United States
     Environmental Protection
     Agency
PRESORTED STANDARD
 POSTAGE&FEES PAID
       EPA
  PERMIT NO. G-35
     Office of Research and Development (8101R)
     Washington, DC 20460
     Official Business
     Penalty for Private Use
     $300

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