CENTERS FOR CHILDREN'S ENVIRONMENTAL HEALTH AND DISEASE PREVENTION RESEARCH

Release Date:  September 22, 2000
 
RFA:  ES-00-008
 
National Institute of Environmental Health Sciences
 http://www.niehs.nih.gov
National Center for Environmental Research, U.S. Environmental Protection Agency
 http://www.epa.gov

Letter of Intent Receipt Date:  November 1, 2000
Application Receipt Date:       January 8, 2001
 
PURPOSE
 
The National Institute of Environmental Health Sciences (NIEHS) and the U.S. 
Environmental Protection Agency (EPA) share the common objective of fostering 
research that will ultimately reduce the extent of adverse human health 
effects occurring as a consequence of exposure to hazardous environmental 
agents.  The agencies recognize that these health impacts can be particularly 
detrimental for children due to pronounced differences in nature and extent of 
environmental exposure as well as in functional development when compared to 
adults.  A Federal Executive Order of April 21, 1997, "Protection of Children 
from Environmental Health Risks and Safety Risks," charges agencies to 
consider special environmental risks to children in their activities.  
Accordingly, NIEHS and EPA invite grant applications for new Centers that will 
conduct multidisciplinary basic and applied research in combination with 
community-based research projects to support studies on the causes and 
mechanisms of children's developmental disorders with special emphasis on 
environmental exposures which may put children at risk of these disorders.  

These research Centers will develop innovative strategies to measure relevant 
environmental exposures in children, and conduct research to reduce hazardous 
exposures and their adverse health effects, and eventually decrease the 
prevalence, morbidity, and mortality of environmentally related childhood 
diseases.  The purpose of awards in this program of Centers for Children's 
Environmental Health and Disease Prevention Research is to:
 
o  Provide for multidisciplinary interactions among basic, clinical, and
behavioral scientists interested in establishing outstanding, state-of-the-art 
research programs addressing environmental contributions to children's health 
and disease.
 
o  Support a coordinated program of research/prevention Centers pursuing high 
quality research in environmental aspects of children's disease, with the 
ultimate goal of facilitating and accelerating translation of basic science 
knowledge into clinical applications or intervention strategies that can be 
used to reduce the incidence of environmentally related diseases in childhood. 
  
o  Develop fully coordinated programs that incorporate exposure assessment and 
health effects research with development and validation of risk management and 
health prevention strategies.
 
o  Establish a national network that fosters communication, innovation, and 
research excellence with the ultimate goal of reducing the burden of morbidity 
among children as a result of exposure to harmful environmental agents.
 
This initiative will focus on the impact of environmental exposures on the 
etiology and prevention of developmental disorders in children.  Data will be 
generated in a multitude of scientific disciplines in order to understand the 
impact of chemical and other exposures on the fetus and child as it relates to 
brain and organ system development, growth and development of the child 
through young adulthood, and neurobehavioral outcomes which have public health 
importance in children.  

This initiative builds upon a related Request for Applications (RFA), which 
resulted in creation in 1998, of eight Centers for Children's Environmental 
Health and Disease Prevention Research (see below).  The prior RFA emphasized 
three research foci: respiratory disorders; growth and development; learning 
and behavior.  The present initiative will support new Centers, specifically 
addressing developmental disorders.

Expansion of the existing program will provide for additional Centers which 
focus on the rising prevalence and incidence of cognitive, motor, sensory, and 
behavioral impairments in children and the environmental exposures of  
children which may put them at risk of these disorders.  

The long-range goals of this program are twofold: to stimulate new research on 
the role of environmental exposures in the etiology and prevention of 
developmental disorders in children; and to promote translation of basic 
research findings into applied intervention and prevention methods, thereby 
enhancing awareness among children, their families, and health care 
practitioners regarding detection, treatment, and prevention of 
environmentally related diseases and health conditions.  In this regard, it is 
required that each Center have a community-based participatory research (CBPR) 
project which capitalizes on partnerships between researchers and community-
based organizations, including local affiliates of organizations which provide 
support and education for families with children with developmental 
disabilities (e.g. March of Dimes, National Alliance for Autism Research and 
The Arc of the United States.)  Each Center should create a structure to carry 
out research which is of importance to the affected community.  This work can 
be community-based etiologic research, community-based exposure assessment 
research, or community-based prevention/intervention research.  

Each application is to be designed around a central scientific theme, 
specifically examining the role of environmental agents in the etiology of 
developmental disorders and design of strategies to prevent them.  The 
application must contain a minimum of two basic biomedical research projects 
and one CBPR project.  These projects must include at least two of the three 
scientific disciplines encompassed by this initiative: mechanistic research, 
epidemiologic research or exposure assessment research. 
 
HEALTHY PEOPLE 2010
 
The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas.  This Request for Applications (RFA), 
"Centers for Children's Environmental Health and Disease Prevention Research," 
is related to the priority area of Environmental Health.  Potential applicants 
may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople/

DESCRIPTION OF CURRENTLY FUNDED NETWORK OF CHILDREN=S ENVIRONMENTAL HEALTH 
CENTERS

In 1998, NIEHS and EPA funded eight universities to initiate this program.  
Four of the Centers are studying the relationship between indoor and outdoor 
air pollutants and childhood asthma.  The other Centers are studying effects 
of exposure to pesticides and other contaminants on growth, development, 
learning, and behavior in both agricultural and inner city settings.  More 
information about the existing program can be found at 
http://www.niehs.nih.gov/dert/programs/translat/children/children.htm

THE EPA CHILDREN'S ENVIRONMENTAL HEALTH INITIATIVE
 
The EPA recognizes that children's environmental health issues are a top 
priority and must become a central focus of the agency's efforts.  This RFA is 
a component of the EPA's overall initiative that, together with the efforts of 
partner agencies, will ensure that children receive the protection they need 
and deserve and help our nation fulfill its obligation to protect future 
generations.  Potential applicants may obtain a copy of the EPA's national 
agenda to protect children's health from environmental threats (EPA 
175-F-96-001) at http://www.epa.gov/enviroed/oeecat/docs/1068.html.

ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic non-profit organizations, public and 
private, that meet the requirements stated in this RFA.  Minority individuals, 
persons with disabilities, and women are encouraged to apply as Principal 
Investigators.  The need for communication and interaction among awarded sites 
dictates that only domestic institutions in the United States will be eligible 
for these Center grant awards.
 
MECHANISM OF SUPPORT
 
This RFA will use the National Institutes of Health (NIH) Program Project 
Grant (P01) or the Environmental Protection Agency's (EPA) Office of Research 
and Development, STAR (Science to Achieve Results) program administered in 
accordance with 40 CFR Part 30 and 40.  Responsibilities for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant.  Policies that govern grant award programs of each agency will 
prevail for respective sources of support.  Support of grants pursuant to this 
RFA is contingent upon receipt of a sufficient number of applications of high 
scientific merit and of appropriated funds for this purpose.
 
Because the nature and scope of the research proposed in response to this RFA 
may vary, it is anticipated that the size of the awards will also vary within 
the funding limits available (see Description of a Center).  The maximum award 
will be $1 million in direct costs in the first and all subsequent years for 
all new Centers.  Funding in subsequent years is contingent upon satisfactory 
progress during the preceding year and availability of funds.

The total project period for an application submitted in response to this RFA 
may not exceed five years.  This RFA is a one-time solicitation.  Future 
unsolicited competing continuation applications will compete with all 
investigator-initiated applications and be reviewed according to the customary 
peer review procedures.  The anticipated award date is July, 2001.
 
FUNDS AVAILABLE
 
Although this solicitation is included in fiscal plans of EPA and NIEHS for FY 
2001, support for these Center grants is contingent upon availability of funds 
for this purpose.  It is anticipated that an estimated total of $6 million, 
including direct and facilities and administrative (F&A) costs, will be 
available for the first year of the program, which will support up to four 
Centers in FY 2001.  It is expected that NIEHS and EPA may solicit additional 
new Center applications in the future through subsequent issuance of a similar 
RFA addressing children's
environmental health.
 
RESEARCH OBJECTIVES
 
Background

The current initiative continues NIEHS= and EPA's intent to foster 
advancements in children's health through enhancing our understanding of 
health impacts of children=s contact with environmental chemicals and other 
exposures in the course of their daily lives by supporting the highest quality 
research on basic disease mechanisms and promoting community-based 
research/prevention activities.  Both agencies are interested in reducing  
risks to children and the societal burden of developmental and behavioral 
disorders or deficits in traits associated with such disorders by preventing 
hazardous environmental exposures at home, at school and in the community. 

Collaborative, multidisciplinary research approaches are required to explore 
the dynamic interaction of children with their environment.  This Center 
program therefore emphasizes integration of basic laboratory science with 
applied CBPR strategies.  Because the latter are also research projects, it is 
important to note that each community based research project should include 
appropriate methodology for assessing its effectiveness (see 'Description of a 
Center' below).  Centers are expected to have fully coordinated programs that 
incorporate exposure assessment and health effects research with development 
and validation of risk management and health prevention strategies.  Moreover, 
involvement of the affected community in planning, implementing, and 
evaluating a CBPR effort is essential.  CBPR not only expands our 
understanding of the causes and remedies of environmentally related disorders, 
but also enhances the capacity of communities to participate in processes that 
shape research and intervention approaches.  By bridging gaps between basic 
and applied researchers and between institutional researchers and community 
members, this program aims to improve our knowledge regarding detection, 
treatment, and prevention of environmentally related diseases in children.

A Center should identify a central theme or focus of its research effort so 
that the subprojects involved are responsive to the specific research area of 
children's environmental health supported by this grant program.  Furthermore, 
the translational objective of this program requires the applicant to include 
at least one subproject which includes research of a community-based 
participatory nature.  

Research Scope

There is growing evidence suggesting that the daily challenges associated with 
productive participation in school and community life are becoming unusually 
difficult for an increasing number of our nation=s children. (Schettler T, 
Stein J, et al, "In Harm=s Way: Toxic Threats to Child Development, 2000" 
http://www.igc.org/psr)  More and more children struggle with learning, 
participation in social groups, self-control and self-regulation issues, and 
face physical challenges involving  gross and fine motor skills.  The number 
of children nation-wide receiving special educational and other services has 
increased dramatically.  Over the period 1977-1994, the number of children 
receiving services for learning disabilities has nearly doubled.  It is now 
estimated that approximately 12 million children, or 17 percent of the U.S. 
population under 18, have one or more learning, behavioral or developmental 
disabilities.  Attention deficit hyperactivity disorder affects three to six 
percent of school-aged children; some investigators have reported prevalence 
estimates as high as 17 percent.  There have been dramatic increases in the 
numbers of children diagnosed with autism and other pervasive developmental 
disorders, an increase of 210 percent in a California registry between 1987-
1998.  Although new programs have been developed to identify and serve the 
needs of these children, the causes of these learning, behaviors and 
developmental challenges are not known.  Past efforts have focused on 
understanding the causes of structural deficits and malformations, some of the 
most severe developmental disorders.  Little attention has been paid to the 
causes of functional deficits, those changes in learning, behavior, and 
development which compromise a child=s ability to function adequately in 
society.  

The causes of developmental disorders and the associated spectrum of deficits 
in traits which make up the disorders are the results of a complex web of 
interactions between genetic, neurochemical, biochemical, environmental, and 
social factors that influence children during critical periods of development. 
 Toxic stressors during development may produce physiological changes which 
have lifelong effects on children=s physical and mental health.  For instance, 
brain development begins before birth and continues through adolescence and 
young adulthood.  During specific time windows, the brain receives different 
types of information which is essential for continued development. Alterations 
in this information will influence how and to what extent different functional 
areas develop within the brain and other organs and how they will impact 
physical and mental health of the human. In order to understand these complex 
processes, the knowledge base on the extent of and timing of children=s 
exposures to chemicals and other toxicants in the environment, factors that 
modify their effects, and the subsequent health outcomes needs to be greatly 
expanded.

Evidence from animal studies has been accumulating on the neurotoxic and 
developmental effects of a variety of chemicals and metals that commonly occur 
in our environment.  Because of the unique sensitivity and vulnerability of 
children, their biologically relevant exposures may be higher than adults and 
hence subtle functional attributes may be affected by such exposures.  It is 
well known that lead is neurotoxic in children and has been shown to be 
responsible for decrements in IQ and intellectual functioning in many cohorts 
around the world.  The potential behavioral consequences of hazardous 
environmental exposures, such as attention deficits, increased impulsiveness, 
overall reduced school performance, aggression and violent behavior, are less 
well studied, but worthy of further attention.  Children=s exposure to methyl 
mercury has been implicated in language, memory and attention impairments, all 
of which may be related to school performance and ability to function in 
society.  Manganese, important in many endogenous enzymatic processes, is 
less-known as a neurotoxicant.  Yet animal studies point to the plausibility 
of exposure to metals as causal agents in hyperactivity or learning 
disabilities.  Many forms of pesticides may pose a significant hazard to 
children since studies have shown that small single doses of organophosphorus 
and pyrethroid insecticides  in a critical window of development may cause 
hyperactivity and changes in neurotransmitter levels in the brain.  Other 
classes of pesticides may cause decreases in DNA synthesis and cell death in 
vital regions of the brain.  More work in populations of children exposed to 
these agents is needed in order to corroborate these findings in humans.  
Similar effects may also be attributable to solvent exposure during pregnancy. 
 Exposures to dioxin and PCBs continue to be of interest since they 
bioaccumulate and are persistent in children during a period of rapid growth 
and development.  Endocrine disrupting chemicals may be related to changes in 
the timing of pubertal development in boys and girls, and may affect later 
reproductive health in adulthood. Additional work using appropriate animal 
models is necessary to further our understanding of these effects, as is new 
work in human populations with unique exposures.  

Over the past three years, NIEHS and EPA have supported and conducted a series 
of workshops to review the state of the science and form recommendations for 
creating a research agenda for understanding the role of environmental agents 
and their modifying factors as possible causes for developmental disorders or 
functional deficits in children.  These workshops have identified 
opportunities for future research which include:  basic mechanistic research 
to understand the underlying structural and functional pathology of these 
disorders; expansion of neurodevelopmental toxicology and behavioral 
neurotoxicology; broadening our understanding of the critical periods of 
development and the timing and mechanisms by which neurotoxic chemicals may 
act to contribute to these disorders in children; and gaps in our knowledge 
related to exposure assessment in children.  These meetings are listed below 
with website links to the proceedings published for the first three in 
Environmental Health Perspectives, Volume 108, Supplement 3, June 2000. 
(http://ehpnet1.niehs.nih.gov/docs/2000/suppl-3/toc.html)

o  The Role of Environmental Neurotoxicants on Developmental Disabilities, 
September 23-25, 1998, University of Rochester, Rochester, NY.

o  Environmental Influences on Children: Brain, Development and Behavior, May 
24-25, 1999, Mount Sinai School of Medicine, New York, NY.

o  Critical Windows of Exposure for Children=s Health, September 14-16, 1999, 
Richmond, VA.  

o  The Role of Human Exposure Assessment in the Prevention of Environmental 
Disease, September 22-24, 1999, Rockville, MD.

The NIEHS and EPA are very interested in the effects of a variety of hazardous 
chemical agents on the growth and development of the fetus and child though 
young adulthood.  These include: pesticides,such as organophosphates, 
triazines, and pyrethroids; chemicals which exhibit endocrine disrupting 
effects, including phthalates, PCBs and dioxins; metals, including mercury, 
chromium, arsenic, and manganese; solvents; polycyclic aromatic hydrocarbons; 
environmental tobacco smoke and particulates and other chemical air 
pollutants.  Other factors which affect the early environment of children, 
such as social and emotional factors, nutritional status, and socioeconomic 
variables should also be included as important components of the proposed 
research.  Research which addresses the interaction between social factors and 
physical environmental factors is encouraged. 

For the purposes of this RFA, neurobehavioral and behavioral disorders include 
(but are not limited to): mental retardation; learning disabilities; cerebral 
palsy; autism and pervasive developmental disorders; visual and hearing 
impairments; attention deficit and hyperactivity disorders; antisocial conduct 
and other behavioral disorders.  Research on specific delays and impairments 
in cognitive, fine and gross motor, sensory function, language development, 
self-regulation and control, and social participation is appropriate.  Also 
included is growth and development of children, including overall size and 
stature, specific organ growth and function, and the regulations of hormonal 
and growth factors important in development.  Puberty and sexual maturation in 
children is of particular interest.  Basic research on the pathophysiology, 
molecular biology and clinical characteristics of these disorders is 
appropriate if it is well integrated into the overall theme of the Center.

The following specific topics are examples of research areas that will be 
suitable, for purposes of the current RFA.  Other research topics should be 
discussed with program staff listed in the INQUIRIES section of the RFA. 

o  Mechanistic neurodevelopment and neurotoxicology of the fetus and growing 
child: 

CNS research during fetal development and childhood;
Signal transduction pathways related to development;

Mitochondrial function in syndromes resulting in developmental disorders;
Genomic imprinting;
Pertubations in thyroid function and effects of development;
Molecular genetics of developmental disorders and associated traits.

o  Population Based Studies:

Estimates of the disease prevalence and incidence and evaluation of risk  
factors for specific developmental disorders and associated traits;
Gene-environment interactions in populations of children with unique 
exposures;
Development of neurochemical and physiological biomarkers of early cognitive 
or developmental function and their application in epidemiologic studies of 
risk;
Use of biomarkers as internal measures of exposures in children.

o  Exposure Assessment in Children:

Characterization of the microenvironments of children at home, school and in 
the community;
Improved quantification of direct and indirect measurements of toxic exposures 
in children using new technology and biomarkers;
Creation of appropriate physiologic-based-pharmacokinetic (PBPK) models of 
chemical metabolism and clearance in children. 

o  Community-Based Participatory Research:

Surveys which estimate the prevalence of developmental and behavioral 
disorders of concern in the community;
Quantification of social factors which put young children at risk of 
challenging behaviors or developmental delays;
Nutritional or other interventions which reduce body burden to specific 
chemicals or metals;
Development of community-based surveillance systems to improve case-
ascertainment in exposed populations;
Measurement of exposures which are of concern to the community using new 
technology or strategies.

Description of a Center
 
A Center for Children=s Environmental Health and Disease Prevention Research 
provides the opportunity for investigators to engage in interdisciplinary and 
collaborative research directed toward a central theme. Research should be 
planned to investigate gaps in knowledge about developmental disorders and 
associated deficits in cognitive, motor, sensory and behavioral traits and the 
effects of exposures to environmental agents during critical windows of 
development including gestation, early childhood, and adolescence. 

All applicants must form a partnership with a community-based organization 
including those which provide support and education to families with children 
with developmental disorders, in order to include a CBPR project within the 
Center.  The foundation of the CBPR should be strongly linked to the basic 
science research within the Center.  In situations where linkages between 
environmental exposures and developmental endpoints are known or strongly 
suggested based on previous research, intervention programs to reduce the 
exposures and show tangible improvements in physiologic or psychologic 
endpoints should be included in the application.  In situations where these 
linkages are not firmly established in human populations but may be 
biologically plausible based on experimental or wildlife research, community 
driven participatory research can be proposed which seeks to describe levels 
of environmental contaminants in the community or health effects about which 
the community is concerned.  The basic science studies should be driven by the 
needs of the community-based research project.  In addition, a Center may 
include facility and administrative core units to provide services to the 
various research projects and to support the organizational and administrative 
aspects of the program.
 
The minimal requirements for a Center for Children's Environmental Health and 
Disease Prevention Research are described below.
 
Each Center will propose an overall research mission and plan that is 
responsive to the objectives of the Center Program set forth in the RFA (see 
Research Objectives above).
 
Each Center will support at least two basic research projects and one 
community based participatory research project.  These three projects must be 
chosen from at least two of the following three disciplines: (1) basic 
mechanistic research; (2) epidemiology; and (3) exposure assessment and 
analysis.  

Basic research projects should include mechanistic studies of environmental 
agents which contribute to adverse health outcomes in children as well as 
research which will improve our basic understanding of pathophysiology, 
molecular genetics, or cell biology of the developmental processes of 
interest.  Basic mechanistic research pertaining to the central theme may fall 
into any of the following disciplines: toxicology, cell and molecular biology, 
 physiology, psychology, and genetics or other relevant fields.  These 
projects  may include methods using animal models, in vitro systems, and/or 
human clinical specimens.  Epidemiologic research should focus on exploring 
the plausibility of environmental contributors and other risk factors for 
specific developmental disabilities or their associated traits.  Population-
based research which explores genetic susceptibility using methods which 
incorporate gene and environmental interactions while quantifying risk is also 
encouraged.  Novel approaches to exposure assessment in exposed and affected 
children across the life span are greatly encouraged.  Development of and 
enhancements to state of the art approaches to direct and indirect 
measurements of exposure to toxic chemicals in children are desired.  Studies 
focusing on characterizing pathways of exposure; the magnitude, frequency, 
duration and time-pattern activities which lead to contact in children, and 
quantifying contact rates of children with exposure media, contaminant 
transfer efficiencies and uptake rates in children are all considered 
important advances in this field.  Interactions between investigators 
responsible for basic research and community-based research projects are 
expected to strengthen the research, enhance transfer of fundamental findings 
to an applied setting, and identify new research directions. (It is 
anticipated that a Center will devote 30-40 percent of its budget to basic 
research projects.)

Each Center must support one project that develops, implements, and evaluates 
a CBPR project related to the central theme of the Center.  These projects can 
be proposed in the following areas: community-based etiology studies of health 
concerns; community-based exposure assessment; and community based 
prevention/intervention research.  It is a requirement of this program that 
academic researchers work together with community-based organizations, broadly 
defined to include environmental justice groups, church coalitions, parent-
teacher associations, or other such groups who have organized around 
environmental or health concerns of the community.  Working with local 
affiliates of regional or national disease-based organizations in identifying 
research concerns is also appropriate.  Applications lacking a demonstrable 
linkage to a community-based or local disease-based organization will be 
considered nonresponsive.

It is expected that Centers working in areas where exposure-disease linkages 
are well established will propose intervention/prevention activities which 
seek to reduce exposures in the environment and subsequently reduce body 
burden and impact of the disease or its associated functional deficits.  CBPR 
should be placed within the appropriate public health context.  For Centers 
addressing areas in which there remains a need to establish exposure-disease 
linkages, the CBPR project can be related to etiology or exposure assessment 
based upon community concerns.  

It is important to note that this CBPR project must specifically address all 
of the following parameters: (a) scientific basis of the proposed research and 
the hypothesis to be tested; (b) sample size needed, power considerations, 
procedures for sample selection, and recruitment and retention of a study
population; (c) detailed description of a research design for the proposed 
intervention or etiologic or exposure assessment study; (d) measurement 
instruments and their reliability and validity, considering both process and 
outcome evaluation; (e) data management and analysis methods; (f) 
identification and description of target community and known environmental 
health hazards; (g) means of establishing effective interaction and 
collaboration with community members.  Because this project is intended to be 
community-based, the application must demonstrate a specific, existing linkage 
to a community-based organization and specific involvement of community 
members in development, conduct, and interpretation of the research.  NIEHS 
and EPA recognize that local health departments often play an important role 
in delivering public health services to the community.  Therefore, applicants 
are also encouraged to consider including local, county, or state health 
departments in the proposed CBPR project.  However, involvement of a local 
health department will not substitute for the required community-based 
organization. 

Activities conducted under this RFA should be consistent with Federal 
Executive Order No. 12988 entitled, "Federal Actions to Address Environmental 
Justice in Minority Populations and Low-Income Populations", when appropriate. 
 To the extent practicable and permitted by law, grantees shall make achieving 
environmental justice part of their project's mission by identifying and 
addressing, as appropriate, disproportionately high and adverse human health 
effects of environmental contaminants on minority, low-income, and medically
underserved children, including but not limited to, African, Hispanic, Asian, 
and Native Americans.

(It is anticipated that a Center may devote 20-35 percent of its budget to one
community-based participatory research project.)
 
Each Center may support facility cores that provide a technique, service, or 
instrumentation that will enhance ongoing research efforts.  Examples of such 
facilities are animal resources, cell/tissue culture, pathology, 
biostatistics, molecular biology, neuropsychology, neuroimaging, analytical 
chemistry, exposure assessment, survey analysis, etc.  It should be noted that 
exposure assessment as a service within a facility core differs in depth and 
scope from the basic research of an exposure assessment research project.  An 
exposure assessment facility core supports the measurement aspects of an 
epidemiologic or other field study by collecting specimens and measuring 
chemical analytes or other biomarkers of exposure to assess environmental 
levels or human body burden of exposures of interest.  This core should be 
involved in quality assurance and/or quality control aspects of exposure 
analysis activities.  (Exposure assessment research activities are described 
in Description of the Center section.)

Budgeted Center projects as well as research projects external to the Center 
may have access to facility cores.  The application should provide a total
operational budget for each facility core together with the percentage of 
support requested from the Center grant.  In addition, the Center must have in 
place and adequately described in the application management policies which 
ensure that budgeted Center projects are given highest priority in receiving 
services provided by the facility core.  The application should explain the 
organization and proposed mode of operation of each core, including a plan for
usage, priority setting, allocation of resources, and any applicable charge 
back system. (It is anticipated that a Center will devote 10-20 percent of its 
budget to facility cores.)

An administrative core unit must provide overall oversight, coordination, and 
integration of Center activities.  An External Advisory Committee to the 
Center Director must be established.  This group should consist of a group of 
three to five scientists, having expertise appropriate for the Center's 
research focus, plus one representative from a community-based organization 
involved in community-based research.  Representation from a state or local 
health department is also encouraged.  At least 67 percent of Committee 
members should be from outside the grantee institution.  The membership of the 
advisory committee must be approved by the funding agency.  The function of 
this Committee is to assist in evaluating the merit, value, and contribution 
of research projects; the relevance and importance of individual 
organizational elements to accomplishing the overall goals of the Center; and 
the effectiveness of the newly recruited Center scientist program. (It is 
anticipated that a Center will devote 10-15 percent of its budget to an 
administrative core.)
 
To attract new investigators into children's environmental health research, 
each Center is encouraged to partially support up to two newly recruited 
Center scientists.  Up to $70,000 per year, direct cost, may be used for each 
newly recruited Center scientist to provide up to 75 percent salary support, 
technical support, equipment, and supplies.  The duration of support as a 
newly recruited scientist is limited to two years.  Following termination of 
support as a newly recruited Center scientist, such an individual may, if
appropriate, become or continue to be a part of a basic or community-based 
participatory research project and make use of Center facilities.  Recruitment 
of women and underrepresented minority scientists is specifically encouraged. 
 To the extent possible, the types of individuals sought and their expected 
roles should be described in the application if specific individuals have not 
been identified. (It is anticipated that a Center will devote no more than
14 percent of its budget to recruitment of new scientists.)

SPECIAL REQUIREMENTS

Annual Meetings: Annual meetings, to be held in Washington, DC or Research 
Triangle Park, NC, are planned for the exchange of information among 
investigators.  Applicants must budget travel costs associated with these 
meetings for the Principal Investigator and each project director in their 
applications. 

Information Exchange: In addition, since these Centers include community-based 
research, applicants are expected to maximize opportunities for information 
exchange between institutional researchers and community members.  As part of 
this program, applicants must generate a report that describes community 
input, program implementation, and relevant findings.  This report must be 
produced at least annually and distributed among community members in such a 
way that it can be easily comprehended by the public.  Applicants must budget 
for production and dissemination of such reports.  This requirement is 
intended to establish a minimal level of communication among project 
participants; additional, more frequent dissemination efforts may be 
appropriate.

Quality Assurance Statement:  EPA regulations as stated in 40CFR30.54 require 
the inclusion of a Quality Assurance Narrative Statement (QANS, OMB # 
2080-0033, approved 8/14/97) for any project application involving data 
collection or processing, environmental measurements, and/or modeling.  The 
QANS provides information on how quality processes or products will be 
assured.  While applications to NIEHS/NIH cannot be considered incomplete 
without this statement, EPA cannot fund any application without a reviewed 
QANS; therefore it is requested that the QANS be included with all 
applications.  For awards that involve environmentally related measurements or 
data generation, a quality system that complies with the requirements of 
ANSI/ASQC E4, "Specifications and Guidelines for Quality Systems for 
Environmental Data Collection and Environmental Technology Programs," must be 
in place.  The Quality Assurance Statement should not exceed two pages.  This 
Statement should, for each item listed below, present the required 
information, reference the specific page and paragraph number of the project 
description containing the information, or provide a justification as to why 
the item does not apply to the proposed research.

1.  Discuss the activities to be performed or hypothesis to be tested and  
criteria for determining acceptable data quality.  (Note: Such criteria may be 
expressed in terms of precision, accuracy, representativeness, completeness, 
and comparability or in terms of data quality objectives or acceptance 
criteria.  Furthermore, these criteria must also be applied to determine the 
acceptability of existing or secondary data to be used in the project.  In 
this context secondary data may be defined as data collected for other 
purposes or from other sources, including the literature, compilations from 
computerized data bases, or results from mathematical models of environmental 
processes and conditions.)

2.  Describe the study design, including sample type and location 
requirements, all statistical analyses that were or will be used to estimate 
the types and numbers of samples required for physical samples, or equivalent 
 information for studies using survey and interview techniques.

3.  Describe the procedures for the handling and custody of samples, including 
sample collection, identification, preservation, transportation, and storage.

4.  Describe the procedures that will be used in the calibration and 
performance evaluation of all analytical instrumentation and all methods of 
analysis to be used during the project.  Explain how the effectiveness of any 
new technology will be measured and how it will be benchmarked to improve an 
existing process, such as those used by industry.

5.  Discuss the procedures for data reduction and reporting, including a 
description of all statistical methods with reference to any statistical 
software to be used to make inferences and conclusions; discuss any computer 
models to be designed or utilized with associated verification and validation 
techniques.

6.  Describe the quantitative and/or qualitative procedures that will be used 
to evaluate the success of the project, including any plans for peer or other 
reviews of the study design or analytical methods prior to data collection.

ANSI/ASQC E4, "Specifications and Guidelines for Quality Systems for 
Environmental Data Collection and Environmental Technology Programs," is 
available for purchase from the American Society for Quality, phone 1-800-248-
1946, item T55.  Only in exceptional circumstances should it be necessary to 
consult this document. 

Successful Center award recipients must complete an overall Center Quality 
Management Plan (QMP) which is a detailed policy statement describing the 
management and technical activities necessary to plan, implement, and assess 
the effectiveness of quality assurance and quality control within the Center. 
 Instructions for preparation of the QMP will be provided at the time of 
award.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
 
It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of 
the research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43.)

All investigators proposing research involving human subjects should
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," published in the NIH Guide for Grants and 
contracts on August 2, 2000 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html; a complete 
copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines: on the Inclusion of Children as Participants in 
Research Involving Human Subjects that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators may also obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted.  Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
subsequent applications, the information that it contains allows EPA and NIEHS 
staff to estimate potential review workload and to plan the review.

The letter of intent is to be sent by the letter of intent receipt date listed 
to:

Linda Bass, Ph.D.
Scientific Review Administrator
Scientific Review Branch
Office of Program Operations
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, EC-24
111 T. W. Alexander Drive
Research Triangle Park, North Carolina 27709
Telephone: 919-541-1307
Fax: 919-541-2503
E-mail: bass@niehs.nih.gov
 
APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, Email: 
GrantsInfo@nih.gov

Content of Applications
 
A response to this RFA should consist of an application that includes a 
detailed description of a Center for Children=s Environmental Health and 
Disease Prevention Research, consisting of at least two individual basic 
research projects, a community-based participatory research project, an 
administrative core, up to two newly recruited Center scientists, and, if 
applicable, one or more facility cores.  The proposed research plan should 
present the applicant's perception of the Center's organization and component 
functions.  This plan should demonstrate the applicant's knowledge, ingenuity, 
practicality, and commitment in organizing a multiproject research 
infrastructure for conducting basic and applied studies in children's 
environmental health sciences.  The research plan for the Center and all 
component projects must address the "Research Scope" described earlier.

For individual projects or cores, page limits stated in the PHS 398 
instructions must be followed.  The overall Center application must also use 
the PHS 398 format to provide at the beginning of the application an overall 
summary of the Center's organization and cumulative aggregate budgeting for 
various research subprojects and cores.  All information essential for 
evaluation of the application must appear in the body of the application 
rather than in an appendix.

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note that this is in pdf format.

To simplify administration of this joint NIEHS/EPA initiative, submit a 
signed, typewritten original of the application, including the Checklist, and 
three signed, photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
 
At the time of submission, three additional copies of the application must be 
sent to:

Linda Bass, Ph.D.
Scientific Review Administrator
Scientific Review Branch
Office of Program Operations
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, EC-24
111 T. W. Alexander Drive
Research Triangle Park, North Carolina 27709
Telephone: 919-541-1307
Fax: 919-541-2503
E-mail: bass@niehs.nih.gov

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique. 

REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIEHS and EPA staff.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further consideration. 
 Any application that does not meet the minimum requirements as set forth in 
the 'Description of a Center' section of this RFA will be considered 
unresponsive to the RFA and returned to the applicant.  This includes, but is 
not limited to, an evaluation by EPA and NIEHS Staff of the program relevancy 
of the proposed basic research and community-based participatory research 
projects.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NIEHS and the EPA in accordance with the review criteria stated below.  As 
part of the initial merit review, all applications will receive a written 
critique and undergo a process in which only those applications deemed to have 
the highest scientific merit, generally the top half of the applications under 
review, will be discussed, assigned a priority score, and receive a second 
level review by both EPA's National Center for Environmental Research (NCER) 
and the NIEHS National Advisory Environmental Health Sciences Council 
(NAEHSC).

Review Criteria
 
Evaluation of applications will be based upon the following:
 
1.  Research Plan
 
Scientific and technical merit of each proposed basic research project, 
including originality, feasibility, innovation, and adequacy of experimental 
design.
 
Scientific and technical merit of the proposed community-based participatory 
research study, including the extent of community sanction, interaction, and 
participation.  Extent to which the design demonstrates sensitivity to 
cultural and socioeconomic factors in the community.  Demonstration of 
effective communication channels between institutional researchers and 
community members.  Plans for useful and practical dissemination of findings 
within the affected community.  Adequacy of statistical and analytical 
methods, data management, and process and outcome evaluation measures.
 
Integration of basic and community based research into a coherent enterprise 
with adequate plans for interaction and communication of information and 
concepts among investigators.

Cohesiveness and multidisciplinary scope of the Center as a whole.  Degree of 
interrelationships, collaboration, and synergism of research that might be 
expected to derive from Center support.  Coordination and interdependence of 
individual projects and their capacity to result in a greater contribution to 
the overall goals of the Center than if each were pursued independently.
 
Adequacy of plans to include both genders and minorities and their subgroups 
as appropriate for the scientific goals of the research.  Plans for 
recruitment and retention of subjects will also be evaluated. (See INCLUSION 
OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS.)

Appropriateness of policies to ensure the protection of human subjects and the 
humane care and use of laboratory animals.
 
2.  Personnel
 
Scientific, administrative, and leadership abilities of the Principal 
Investigator and other key participants, particularly, but not exclusively, in 
the area of the proposed research.  The Principal Investigator should be an 
established research scientist with the ability to ensure quality control and 
the experience to administer effectively and integrate all components of the 
Center.  A minimum time commitment of 25 percent is expected for this 
individual.
 
Documented commitment of time by key personnel for the proposed studies.
 
Procedures established for recruitment and evaluation of new Center 
scientists.  Evidence of efforts to develop novel mechanisms for recruiting 
candidates among women and underrepresented minority investigators.  Potential 
of new Center Scientists to become independent investigators in clinical, 
basic, or community-based participatory research in children's environmental 
health.
 
3.  Facilities and Management

Adequacy of administrative and technical capabilities to conduct the research 
proposed.
 
Scientific and organizational structure of the Center, including adequacy of 
arrangements for external review.
 
Nature and quality of facility cores.  Technical merit, justification, cost 
effectiveness, qualifications of staff, utility to investigators, and 
arrangements for internal quality control, allocation of resources, priority 
of usage, and day-to-day management.

Adequacy of animal facilities and appropriateness of animal care management 
where animal work is proposed.
 
Adequacy of clinical facilities and appropriateness of patient care management 
where clinical work is proposed.  As appropriate, access to inpatient and 
outpatient children's health care units providing adequate numbers of patients 
for research projects that require patient participation. [Applications from 
institutions that have a General Clinical Research Center (GCRC) funded by the 
NIH National Center for Research Resources may wish to identify the GCRC as a 
resource for conducting proposed research.  In such a case, a letter of 
agreement from either the GCRC Program Director or Principal Investigator 
should be included with the application.]
 
Institutional assurance to provide support to the Center in such areas as 
fiscal administration, personnel management, space allocation, procurement, 
planning, and budgeting.
 
4.  Budgeting
 
Appropriateness of the proposed budget and duration in relation to proposed 
research.
 
Schedule
 
The following is the schedule planned for this initiative.  It should be noted 
that this schedule may be changed without notification due to factors that 
were unanticipated at the time of announcement.  Please contact the program 
official listed below regarding any changes in the schedule.
 
Letter of Intent Receipt Date:     November 1, 2000 
Application Receipt Date:          January 8, 2001 
Initial Review Group Peer Review:  March 2001
NAEHS Council/NCER Review:         May 2001
Earliest Award Date:               July 1, 2001

AWARD CRITERIA

The anticipated earliest date of award is July 2001.  Approved applications 
will be considered for award based on scientific and technical merit; program 
balance; and availability of funds.  Funding will be provided to each Center 
by a single award from either EPA or NIEHS or a combination of two separate 
awards.  Administrative and budgetary policies of EPA and NIEHS will apply to 
these awards.

In order to receive funding, an individual domestic institution's application 
for a Children=s Environmental Health Center grant must have two or more
related, interactive, and high quality research subprojects that provide a 
multidisciplinary, yet thematic, approach to the problems to be investigated. 
 Applicants must also include an additional project which is community-based 
and participatory in nature.  Awards to applications or components thereof 
proposing long-term (greater than five years) epidemiological or large-scale 
clinical trial research will not be made under any circumstances.
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic issues to:
 
Gwen W. Collman, Ph.D.
Scientific Program Administrator
Chemical Exposures and Molecular Biology Branch
Office of Program Development
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, EC-21
111 T.W. Alexander Drive
Research Triangle Park, NC 27709
Telephone: 919-541-4980
Fax: 919-316-4606
E-mail: collman@niehs.nih.gov
 
Nigel Fields, M.S.P.H.
National Center for Environmental Research 
U.S. Environmental Protection Agency (8723R)
1200 Pennsylvania Ave., NW
Washington, DC 20460
Telephone: 202-564-6936
Fax: 202-565-2448
E-mail: fields.nigel@epa.gov
 
Direct inquiries regarding fiscal matters to:
 
Ms. Dorothy Duke
Chief, Grants Management Branch
Office of Program Operations
Division of Extramural Research and Training
National Institute of Environmental Health Science
P.O. Box 12233, EC-22
111 T.W. Alexander Drive
Research Triangle Park, NC 27709
Telephone: 919-541-1373
Fax: 919-316-4606
E-mail: duke5@niehs.nih.gov

Mr. Jack Puzak
Deputy Director
National Center for Environmental Research 
U.S. Environmental Protection Agency (8701R)
1200 Pennsylvania Ave., NW

Washington, DC 20460
Telephone: 202-564-6825
Fax: 202-565-2444
E-mail: puzak.jack@epa.gov

AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic Assistance Number 
66.500, 93.113, 93.114 and 93.115.  Awards by NIEHS are made under 
authorization of Sections 301 and 405 of the Public Health Service Act as 
amended (42 USC 241 and 284) and administered under NIH grant policies and 
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. EPA awards are 
made under the authority of 40 CFR Part 30 and 40.  The program is not subject 
to the intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.

The PHS and EPA strongly encourage all grant recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or, in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the EPA and PHS missions to protect and advance the physical and mental
health of the American people.


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