The United States
Environmental Protection
Agency
Office of Research and
Development
Washington, DC 20460
EPA/600/F-96/003
April 1996
&EPA
The United States
Environmental Protection Agency
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Announces
the Availability of
1996 Grants for Research
on
Endocrine Disrupters
Role of Interindividual Variation in Human Susceptibility to Cancer
Risk-Based Decisions for Contaminated Sediments
APPLICATION SUBMISSION CLOSING DATE: MAY 1, 1996
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Introduction
The U.S. Environmental Protection Agency (EPA) invites research grant applica-
tions in the following areas of special interest to its mission:
11. Endocrine disruptors
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12. Role of Interindividual Variation In Human Susceptibility to Cancer
13. Risk-Based Decisions for Contaminated Sediments
This invitation provides relevant background information, summarizes EPA's interest in
the topic areas, and describes the application and review process.
Background
During fiscal year 1995 EPA increased funding for its investigator-initiated re-
search grants program. For fiscal year 1996, EPA anticipates a second increase, sub-
ject to the 1996 Federal appropriation process. In December 1995 EPA issued a Re-
quest for Applications (RFA) which summarized its interest in 9 programmatic areas.
This announcement supplements that RFA and solicits research proposals in 3 addi-
tional topical areas. Additional programs involving cooperation with the National Sci-
ence Foundation and other agencies were announced separately.
EPA Mission and R & D Strategy
The mission of EPA — and its unique role — is the protection of both environ-
mental quality and human health through effective regulations and other policy imple-
mentation. Achievement of this mission requires the application of sound science to the
assessment of environmental problems and evaluation of possible solutions. A signifi-
cant challenge is to support both long-term research that anticipates future environmen-
tal problems as well as to fill significant gaps in knowledge relevant to meeting current
Agency goals. This Request for Applications and the joint solicitations with other agen-
cies are important steps toward ensuring that EPA can provide a sound scientific foun-
dation as the country enters a new generation of environmental protection.
EPA recently reorganized its research programs to focus on the reduction of
uncertainty associated with risk assessment and reduction of risks to human health and
ecosystems. Through its laboratories and through grants to universities and other not-
for-profit institutions, EPA will promote research in both domains, according the highest
priority to those areas where risk assessors are most in need of new concepts, meth-
ods, and data. At the same time, EPA will foster the development and evaluation of new
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risk reduction technologies across a spectrum, from pollution prevention, through end-
of-pipe controls, to remediation and monitoring. In all areas, EPA is interested in re-
search that recognizes issues relating to environmental justice, the Agency's effort to
achieve equal protection from environmental and health hazards for all people without
regard to race, economic status, or culture.
Research Programs of Interest
11. Endocrine Disrupters
Reports have been accumulating that both humans and wildlife species have
experienced adverse health consequences resulting from exposure to environmental
pollutants that interact with the endocrine system. These pollutants are collectively
referred to as "endocrine disrupters," a term broadly defined as "an exogenous agent
that interferes with the production, release, transport, metabolism, binding, action, or
elimination of natural hormones in the body responsible for the maintenance of homeo-
stasis and the regulation of reproductive and developmental processes." The Agency is
concerned with potential effects posed by environmental agents that act as hormones or
anti-hormones, as well as chemicals or mixtures which perturb components of the
endocrine system through as yet uncharacterized modes of action.
To date, problems have been identified primarily in domestic or wildlife species
with high exposure to organochlorine compounds, including DDT and its metabolites,
PCBs and dioxins, some organometals, unidentified components of certain types of
complex effluents and emissions, and/or to naturally occurring plant estrogens.
Whether similar effects are occurring in the general human or wildlife population is
unknown. Several reports of declines in the quality and quantity of sperm production in
humans over the last four decades and reported increases in incidence of certain can-
cers (breast, prostate, testicular) have led to speculation about environmental etiologies.
Correlational evidence suggests that specific populations of animals such as birds, fish,
reptiles, and mammals have been, or currently are being, adversely impacted by expo-
sure to environmental contaminants that may manifest effects through the endocrine
system.
The objective of EPA's Endocrine Disrupter research program is to evaluate
potential health effects associated with endocrine disrupters and to determine the extent
of current exposures. Investigator-initiated grant proposals are sought in four broad
areas: (1) human health effects, (2) ecological health effects, (3) human exposure
evaluations, (4) ecological exposure evaluations.
Examples of research topics of interest to EPA include:
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Refinement of methods to monitor and characterize exposure of humans and/or
wildlife to endocrine disrupters, including aspects such as exposure half-life,
speciation, uptake, and phase equilibrium.
Development and validation of models to estimate exposure to endocrine
disrupters from different sources via multiple pathways.
Development and validation of biomarkers of endocrine disrupter exposure and
effect.
Development and validation of in vitro and short-term in vivo test systems to
screen for chemicals with specific mechanisms of action expressed via different
endocrine pathways; test systems that are applicable across multiple
phylogenetic levels are of particular interest.
Development of Physiologically-Based Pharmacokinetic (PB-PK),
Physiologically-Based Toxicokinetic (PB-TK), and Biologically-Based Dose-
Response (BBDR) models that incorporate key species-specific parameters
critical to the extrapolation of effects across phyla.
Refinement and validation of methods and models that relate effects observed at
subcellular levels to adverse impacts in individuals (both human and wildlife
species) and in wildlife populations.
Funding: Up to $3.5 million is expected to be available in fiscal year 1996 for awards in
this program area. The projected award range is $100,000 - $200,000/year for up to 3
years.
12. Role of Interindividua! Variation in Human Susceptibility to Cancer
Background
In 1994, the National Academy of Sciences released the report, Science and
Judgment in Risk Assessment. This report, which was produced in response to the
Clean Air Act Amendments of 1990, evaluated risk assessment methods at EPA and
drew a series of conclusions and recommendations. Included was the issue of varia-
tion in human susceptibility. On this issue, the report concluded that EPA's consider-
ation of interindividual variability has been limited largely to noncarcinogenic effects,
such as asthmatic responses to sulfur dioxide exposure, and suggested that EPA in-
clude consideration of interindividual variability in its cancer risk assessments. The
MAS recommended that:
(1) Federal agencies should sponsor molecular, epidemiological, and
other types of research to examine the causes and extent of interindividual
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variability in susceptibility to cancer and the possible correlations between
susceptibility and such covariates as age, race, ethnicity, and sex. Results
should be used to refine estimates of risks to individuals and the general
population.
(2) EPA should increase its efforts to validate or improve the default as-
sumption that humans on average have the same susceptibility as hu-
mans in epidemiological studies, the most sensitive animals tested, or
both.
The NAS report stated that human beings vary substantially in their inherent
susceptibility to carcinogenesis, both in general and in response to any specific stimulus
or mechanism. Point estimates of carcinogenic potency of a substance will not apply to
all individuals in the population. They further stated that variability affects each step in
the carcinogenic process (e.g., carcinogenic uptake and metabolism, DMA damage,
DNA repair and misrepair, cell proliferation, tumor progression, and metastasis) and that
the variability arises from many independent factors, some inborn and some environ-
mental. NAS stated that it appeared that some of the individual determinants are dis-
tributed bimodally or perhaps trimodally in the population (e.g., hypersusceptible people
such as those with germ-line mutations in tumor suppressor genes) while other determi-
nants seemed to be distributed more or less continuously and unimodally with either
narrow or broad variances (e.g., the kinetics or activities of enzymes that activate or
detoxify particular pollutants).
Description
In this RFA, EPA is interested in: (1) the identification of human genetic polymor-
phisms which can affect carcinogenic risk from environmental agents, (2) the quantita-
tive relationship of these polymorphisms to the risk of cancer from environmental
agents, and (3) the distribution of such polymorphisms in the general population.
Response to this RFA should address human variation in susceptibility with regard to
polymorphisms and a specific chemical carcinogen of concern to the Agency.
Funding: Up to $2.0M is expected to be available in Fiscal Year 1996 for this program
area. The projected award range is $100,000 - $200,000/year for up to 3 years.
13. Risk-Based Decisions for Contaminated Sediments
Many persistent chemical contaminants in aquatic ecosystems eventually accu-
mulate in sediments where they may adversely affect the benthic biota, become a
source of contamination in the water column, accumulate in biological tissues, and enter
pelagic and human food chains. Contaminated sediments now appear to be the main
source of toxic contaminants in many bays, lakes, and rivers. For example, of the Great
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Lake's 42 Areas of Concern, 33 have degraded water quality problems associated with
contaminated sediments. Because of their potential adverse impacts, the long periods
of time associated with natural assimilation of many in-place contaminants, and the high
costs of mitigation, sediments have become a focus of concern for EPA.
The following areas of research provide the framework for the competition:
Risk-Based Assessments
Hazard Identification
All assessment techniques, either biological or chemical, need validation of their
ability to predict impacts on indigenous aquatic communities. When laboratory data and
test systems are being used to predict contaminated sediment impacts, there needs to
be a strong lab-to-field association. Research is needed to validate these techniques
using a risk-based approach. Validation efforts must consider the uncertainty associ-
ated with the assessment and the degree of protection offered to the aquatic commu-
nity.
The effects of contaminants associated with sediments is often manifested
through aquatic food chains. Research and mathematical modeling is needed to accu-
rately characterize the transfer of toxic substances from their source to the sediments,
from sediments to organisms, and organism to organism.
Dose-Response
Short-term sediment toxicity test methods to examine aquatic life effects using
laboratory animals exist. In addition, there are some theoretical models to predict
whether certain single chemical concentrations will have an adverse impact on benthic
communities. Most contaminated sediments contain mixtures of chemicals; thus, mix-
ture toxicity research and modeling both for organic substances and trace metals are
needed to complement single chemical assessments. Further research is needed to
expand the number and kind of species being tested.
Exposure Assessment
Knowledge of the fate and bioavailability of toxic substances in sediments is
sometimes highly speculative. Additional knowledge is needed on: (1) the fate of toxic
substances during resuspension, especially during severe events, and biological,
chemical and physical factors controlling resuspension of sediments, (2) the spatial
(horizontal and vertical) and temporal extent of sediment contamination, and (3) bio-
geochemical partitioning between sediments, water, and biota to better predict
bioavailability of chemicals believed to have adverse impacts.
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Risk Management
Sediment Treatment
Contaminated sediments requiring treatment can result from either sediment
management operations (e.g., maintenance dredging) or remediation efforts. The
environmental risks associated with these sediments need to be reduced. For example,
better methods to predict the extent to which dredging operations resuspend and trans-
port contaminants to less contaminated areas are needed. Research is needed to
develop innovative treatment options for sites with large volumes of contaminated
sediment (e.g., harbors).
Proposals that address the above mentioned needs are invited. Proposals must
relate how the research will facilitate better risk assessments and risk management
decisions.
Funding: Approximately $2.0 million is expected to be available for awards under this
program area. The projected award range is $100,000 - $200,000/year for up to 3
years.
The Application
Proposed research projects must be designed to advance the state of knowledge
in the indicated areas. The Application Kit for Assistance contains detailed instructions
on how to prepare your application. The application kit is available at most institutional
offices of sponsored research or may be obtained from EPA at:
U.S. Environmental Protection Agency
National Center for Environmental Research and Quality Assurance (8703)
401 M Street SW
Washington DC 20460
Phone: (202)260-3837
Fax: (202)260-2039
Each application must contain the following:
A. Application for Federal Assistance (Standard Forms 424 and 424A). These
forms must have original signature.
B. A detailed, itemized budget for each year of the proposed project.
C. A budget justification describing the basis for calculating the personnel, fringe
benefits, travel, equipment, supplies, contractual support, and other costs
identified in the itemized budget.
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D. An abstract containing the following information: The project title, the names and
affiliations of all investigators, and a summary of the objectives, expected results,
and approach described in the proposal. The abstract must not exceed one (1)
8.5 x 11 inch page of single-spaced standard 12 point type with 1 inch margins.
E. A Description of the Project. This description must not exceed fifteen (15) pages.
All pages must be consecutively numbered, 8.5 x 11 inch, single-spaced
standard 12 point type with 1 inch margins. The description must provide the
following information (1-5):
1. Objectives: List objectives of the proposed research and/or the
hypotheses being tested during the project.
2. Expected Results or Benefits: Describe the results you expect to
achieve during the project and the benefits of success.
3. Approach: Outline the methods, approaches, and techniques that
you intend to employ in meeting the objective stated above.
4. General Project Information: Discuss other information relevant to
the potential success of the project. This might include facilities,
project schedules, proposed management, interactions with other
institutions, etc.
5. Quality Assurance: A brief narrative statement (not to exceed two
consecutively numbered, 8.5 x 11 inch pages of single-spaced
standard 12 point type with 1 inch margins) describing the quality
assurance procedures proposed for the project (see section of this
RFA on quality assurance).
F. Any important attachments, appendices, references, or other information may be
included but must not exceed five (5) pages.
G. The resumes of the principal investigator, and co-workers. Resumes must not
exceed two consecutively-numbered, 8.5 x 11 inch pages of single spaced
standard 12 point type with 1 inch margins.
H. Standard Form (SF) 5700-48 Procurement System Certification (provided in
Application Kit).
I. Standard Form (SF) 5700-49 Debarment and Suspension Certification (provided
in Application Kit).
J. A list of key contacts (provided in Application Kit) including authorizing
representative, payee, administrative contact, and project manager.
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K. Disclosure of Lobbying Activities (provided in Application Kit).
L. Copy of State Clearing House Approval Notification (see Application Kit to
determine if applicable).
M. In lieu of the Application Receipt Letter provided in some Application Kits, the
applicant must include a blank self-addressed, stamped post card with the
application.
The application must contain all of the above, in the order listed.
Sorting Codes
In order to facilitate proper assignment and review of applications, applicants are
asked to identify the topic area in which their application is to be considered. Applica-
tions must be identified by printing the appropriate Sorting Code (see below) in block 10
of the SF-424.
Endocrine Disrupters 96-NCERQA-11
Role of Interindividual Variation in
Human Susceptibility to Cancer 96-NCERQA-12
Risk-Based Decisions for Contaminated Sediments 96-NCERQA-13
The Sorting Code must be placed in Block 10 of SF 424 as shown below:
1 0. CATALOG OF FEDERAL
DOMESTIC ASSISTANCE
NUMBER:
O
0
•
0
O
O
TITLE: 96-NCERQA-X
The Sorting Code must also be included in the address on the package that is submit-
ted to EPA (see next section on how to apply).
How to Apply
To be considered, the original and ten (10) copies of the fully developed research
grant application and five (5) additional copies of the abstract (fifteen in all), must be
received (postmarked if sent by U.S. Mail) by the National Center for Environmental
Research and Quality Assurance no later than 4:00 P.M. EST on the closing date as-
signed to these topic areas, May 1,1996.
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The application and abstracts must be prepared in accordance with instructions
in the Application Kit for Federal Assistance and this RFA. Informal, incomplete, or
unsigned proposals will not be considered. Completed applications should be sent via
regular or express mail to:
U.S. Environmental Protection Agency
Office of Research and Development
National Center for Environmental Research and Quality Assurance (8703)
Sorting Code: 96-NCERQA-X [X=11, 12, or 13]
Room M2426
401 M Street SW
Washington DC 20460
Applications sent via express mail should have the following telephone number listed on
the express mail label: (202) 260-3837
Quality Assurance
Data sets resulting from EPA-funded environmental research often are used by
government officials when establishing standards or when making other policy deci-
sions. Explicit indicators of data quality are essential for determining whether a particu-
lar data set is appropriate for use in a specific context. To that end, EPA regulations
require that grant-funded projects address quality assurance.
The application must include a quality assurance narrative statement, not to
exceed two pages, which for each item listed below, either presents the required infor-
mation or provides justification as to why the item does not apply to the proposed re-
search.
The intended use of the data and the associated acceptance criteria for data
quality (i.e., precision, accuracy, representativeness, completeness, and
comparability).
Project requirements for precision, accuracy, representativeness, completeness,
and comparability, and how these will be determined.
Procedures for selection of samples or sampling sites, and collection or
preparation of samples.
Procedures for sample handling, identification, preservation, transportation,
and storage.
Description of measurement methods or test procedures, with a statement of
performance characteristics if methods are non-standard.
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Standard quality assurance/quality control procedures (e.g., American Society for
Testing Materials, American Public Health Association, etc.) to be followed. Non-
standard procedures must be documented.
Data reduction and reporting procedures, including description of statistical
analyses to be used.
Guidelines and Limitations
Subcontracts for research to be conducted under the grant that exceed 40% of
the total direct cost of the grant for each year in which the subcontract is awarded will
be subject to special review.
Additional Requirements
Researchers will be expected to participate in an annual All-Investigator's Meet-
ing with EPA researchers and other grantees and cooperators to report on research
activities and to discuss issues of mutual interest.
Eligibility
Academic and not-for-profit institutions located in the U.S., and state or local
governments are eligible under all existing authorizations. Profit-making firms are
eligible only under certain laws, and then under restrictive conditions, including the
absence of any profit from the project. Federal agencies and federal employees are not
eligible to participate in this program. Potential applicants who are uncertain of their
eligibility should contact EPA's Grants Operations Branch at (202) 260-9266.
Review and Selection
All grant applications are initially reviewed by EPA to determine their legal and
administrative acceptability and responsiveness to this solicitation. Acceptable applica-
tions are then reviewed by an appropriate technical peer review group. This review is
designed to evaluate and rank each proposal according to its scientific merit. Each
review group is composed primarily of non-EPA scientists, engineers, social scientists,
and/or economists who are experts in their respective disciplines. All reviewers are
proficient in the technical areas that they are reviewing. The reviewers use the following
criteria in their reviews:
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quality of the research plan (including theoretical and/or experimental design,
originality, and creativity);
qualifications of the principal investigator and staff, including knowledge of
relevant subject areas;
potential contribution of the research to advancing scientific knowledge in the
environmental area;
availability and adequacy of facilities and equipment; and
budget justification — justification for equipment will receive special attention;
responsiveness to solicitation objectives.
Funding decisions are the sole responsibility of EPA. Grants are selected on the basis
of technical merit, relevancy to the research priorities outlined, program balance, and
budget.
EPA anticipates making awards from this RFA by September 1996.
Proprietary Information
By submitting an application in response to this solicitation, the applicant grants
EPA permission to share the application with technical reviewers both within and out-
side of the Agency. Applications containing proprietary or other types of confidential
information will be immediately returned to the applicant without review.
Funding Mechanism
The funding mechanism for all awards issued under this solicitation will consist of
a grant between EPA and the recipient. In accordance with Public Law 95-224, a grant
is used to accomplish a public purpose of support or stimulation authorized by Federal
statute rather than acquisition for the direct benefit of the Agency. In using a grant
instrument, EPA anticipates that there will be no substantial involvement during the
course of the grant between the recipient and the Agency.
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Contacts
Additional general information on the grants program may be obtained by
contacting:
U.S. Environmental Protection Agency
National Center for Environmental Research and Quality Assurance (8703)
401 M Street SW
Washington DC 20460
Phone: (202)260-3837
Fax: (202)260-2039
Applicants with technical questions may contact the appropriate individual identified
below.
Contacts for Research Topics of Interest
Endocrine Disrupters
Robert Menzer 202-260-5779
menzer.robert@epamail.epa.gov
Role of Interindividual Variation in
Human Susceptibility to Cancer
David Reese 202-260-7342
reese.david@epamail.epa.gov
Risk-Based Decisions for Contaminated Sediments
David Reese 202-260-7342
reese.david@epamail.epa.gov
•U.S. Government Printing Office: 1996 - 751-819
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