Grantee Research Project Results

U.S. Environmental Protection Agency
Office of Research and Development
National Center for Environmental Research
Science to Achieve Results (STAR) Program

CLOSED - FOR REFERENCES PURPOSES ONLY

Recipients List

Development and Use of Adverse Outcome Pathways that Predict Adverse Developmental Neurotoxicity

This is the initial announcement of this funding opportunity.

Funding Opportunity Number: EPA-G2012-STAR-F1

Catalog of Federal Domestic Assistance (CFDA) Number: 66.509

Solicitation Opening Date: September 13, 2012
Solicitation Closing Date: December 12, 2012 - extended to December 19, 2012, 11:59:59 pm Eastern Time

Eligibility Contact: Bronda Harrison (harrison.bronda@epa.gov); phone: 703-347-8080
Electronic Submissions: Todd Peterson (peterson.todd@epa.gov ); phone: 703-308-7224
Technical Contact: Mitch Lasat (lasat.mitch@epa.gov); phone: 703-347-8099

Table of Contents:
SUMMARY OF PROGRAM REQUIREMENTS
	Synopsis of Program
	Award Information
	Eligibility Information
	Application Materials
	Agency Contacts
I. FUNDING OPPORTUNITY DESCRIPTION
	A. Introduction
	B. Background
	C. Authority and Regulations
	D. Specific Areas of Interest/Expected Outputs and Outcomes
	E. References
	F. Special Requirements
II. AWARD INFORMATION
III. ELIGIBILITY INFORMATION
	A. Eligible Applicants
	B. Cost Sharing
	C. Other
IV. APPLICATION AND SUBMISSION INFORMATION
	A. Internet Address to Request Application Package
	B. Content and Form of Application Submission
	C. Submission Dates and Times
	D. Funding Restrictions
	E. Submission Instructions and Other Submission Requirements
V. APPLICATION REVIEW INFORMATION
	A. Peer Review
	B. Programmatic Review
	C. Funding Decisions
VI. AWARD ADMINISTRATION INFORMATION
	A. Award Notices
	B. Disputes
	C. Administrative and National Policy Requirements
VII. AGENCY CONTACTS

Access Standard STAR Forms (Forms and Standard Instructions Download Page)
View research awarded under previous solicitations (Funding Opportunities: Archive Page)

SUMMARY OF PROGRAM REQUIREMENTS

Synopsis of Program:
The U.S. Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications proposing research that will identify and/or provide a better understanding of adverse outcome pathways (AOPs) that lead to developmental neurotoxicity (DNT). Such research should advance the state of knowledge by linking key events along the continuum from exposure to adverse outcomes, including windows of susceptibility, and ultimately resulting in AOP-based data and models for chemical testing that will allow risk assessors to predict DNT. EPA is particularly interested in funding research projects that focus on endocrine signaling pathways that alter neurodevelopment, but will accept research proposals that address other AOPs.

This solicitation does not provide the opportunity for the submission of applications for projects that involve human subjects research. Human subjects research supported by the EPA is governed by EPA Regulation 40 CFR Part 26 (Protection of Human Subjects). Applications proposing human subjects research will not be considered for funding and will be deemed ineligible.

Human subjects research precluded from this Request for Applications (RFA) includes:

Projects that collect data from or about humans which meet the regulatory definition of research with human subjects and are thereby subject to the requirements of EPA Regulation 40 CFR Part 26 and EPA Order 1000.17 Change A1. This includes projects conducted under programs that are not considered research for other purposes. For example, some demonstration programs and some public health practice programs may include research activities. Projects that utilize surveys about people or contain identifiable private information also constitutes human subjects research and are not allowable under this solicitation. All applications must include a Non-Human Subjects Research Determination (as described in Section IV.B.5.c) verifying that the proposed research will not involve human subjects.

Award Information:
Anticipated Type of Award: Grant or cooperative agreement.
Estimated Number of Awards: Approximately five awards.
Anticipated Funding Amount: Approximately $4 million total for all awards.
Potential Funding per Award: Up to a total of $800,000 including direct and indirect costs, with a maximum duration of four years. Cost-sharing is not required. Proposals with budgets exceeding the total award limits will not be considered.

Eligibility Information:
Public nonprofit institutions/organizations (includes public institutions of higher education and hospitals) and private nonprofit institutions/organizations (includes private institutions of higher education and hospitals) located in the U.S., state and local governments, Federally Recognized Indian Tribal Governments, and U.S. territories or possessions are eligible to apply. See full announcement for more details.

Application Materials:
To apply under this solicitation, use the application package available at Grants.gov (for further submission information see Section IV.E. “Submission Instructions and other Submission Requirements”). The necessary forms for submitting a STAR application will be found on the National Center for Environmental Research (NCER) web site, Forms and Standard Instructions Download Page (https://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms). If your organization is not currently registered with Grants.gov, you need to allow approximately one week to complete the registration process. This registration, and electronic submission of your application, must be performed by an authorized representative of your organization.

If you do not have the technical capability to utilize the Grants.gov application submission process for this solicitation, call 1-800-490-9194 or send a webmail message at least 15 calendar days before the submission deadline to assure timely receipt of alternate submission instructions. In your message provide the funding opportunity number and title of the program, specify that you are requesting alternate submission instructions, and provide a telephone number, fax number, and an email address, if available. Alternate instructions will be emailed whenever possible. Any applications submitted through alternate submission methods must comply with all the provisions of this Request for Applications (RFA), including Section IV, and be received by the solicitation closing date identified above.

Agency Contacts:
Eligibility Contact: Bronda Harrison (harrison.bronda@epa.gov); phone: 703-347-8080
Electronic Submissions: Todd Peterson (peterson.todd@epa.gov ); phone: 703-308-7224
Technical Contact: Mitch Lasat (lasat.mitch@epa.gov); phone: 703-347-8099

I. FUNDING OPPORTUNITY DESCRIPTION

A. Introduction
The U.S. Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications proposing research that will identify and/or provide a better understanding of key adverse outcome pathways (AOPs) that lead to developmental neurotoxicity (DNT). Such research should advance the state-of-knowledge by linking key events along the continuum from exposure to adverse outcomes, identify windows of susceptibility, and ultimately develop data, methods and models that will allow risk assessors to predict developmental neurotoxicity (DNT). EPA is particularly interested in funding research projects that focus on endocrine signaling pathways that alter neurodevelopment, but will accept research proposals that address other AOPs. EPA is also interested in supporting research that will result in tools and methodologies to facilitate the use of AOPs in the development of more efficient approaches for predicting DNT including screening methods.

This solicitation seeks to support research that will: 1) develop and apply new data to characterize AOPs for DNT outcomes; 2) advance the state-of-knowledge on the key events that link exposure to adverse DNT outcomes; and 3) develop methodologies, tools, and models for incorporating research results into risk assessments. The EPA currently supports a number of AOP and systems models research grants resulting from previous solicitations. Information regarding current research can be found on ORD’s National Center for Environmental Research (NCER) web site.

B. Background
B.1. Adverse Outcome Pathways as a Unifying Concept for Predictive Models

A high-priority research area identified by EPA’s Office of Research and Development (ORD) is
the advancement of integrated approaches to develop new prediction techniques including the use of innovative technologies for chemical toxicity testing. Information about EPA’s research program on chemical safety can be found at: Chemical Safety for Sustainability Research.

Many existing chemicals have not been thoroughly evaluated for potential risks to human health and the environment. Currently there is a need for cost-effective predictive tools and testing methods to generate safety information needed to make better-informed decisions about chemicals. The development of innovative methods that allow for faster and more cost-effective assessment of environmental chemicals will benefit the research and risk assessment communities, including those in academia and industry.

A cornerstone of EPA’s ORD research framework is the use of AOPs to enable the development of effective alternative toxicity testing and risk assessment methods for potentially harmful environmental contaminants Framework for an EPA Chemical Safety for Sustainability Research Program. AOPs describe the known linkages along the continuum from the molecular initiating event to adverse outcomes in an individual or a population (Sonich-Mullin et al., 2001; Boobis et al., 2008; Ankley et al. 2009). As such, AOPs outline the sequence of key measurable events, starting an initiating molecular event in which a chemical interacts with a biological target(s); following on through a sequential series of cellular, anatomical and functional changes in biological processes; and ultimately culminating in an adverse outcome of relevance to human or ecological risk assessors (e.g, disrupted neurodevelopment, neurodevelopmental disorders, IQ loss). Of particular importance for DNT is inclusion of susceptible life-stages and critical windows of exposure during development. Characterization of AOPs allows for identification of key events for which high-throughput testing methods can be developed. AOPs also provide important information on the development of structure-activity relationships, i.e., using effects information from one chemical (the source chemical) to predict the effect for another structurally similar chemical (the target chemical) (OECD, 2011). Finally, AOPs provide evidence important for qualitative and quantitative predictive models of the adverse outcomes that result from triggering molecular initiating or other key events.

B.2. Adverse Outcome Pathways for Developmental Neurotoxicity in Humans and Other Species

There is a critical need to develop alternative testing methods that allow for more rapid testing of chemicals for DNT potential (Lein et al., 2007; Coecke et al., 2007; Crofton et al., 2011). While there are a large number of cellular and molecular processes known to be critical to proper development of the nervous system, there are relatively few examples of a comprehensive understanding of a pathway leading from chemical exposure to adverse neurodevelopmental outcomes. The lack of AOPs hampers the development of alternative testing methods and limits the predictive ability of high-throughput chemical testing. In assessing DNT, additional complexity is added by the developmental stage (or window of susceptibility) at which the organism is exposed to the chemical as well as the biological complexity of the exposed organism or experimental system. These spatially and temporally dependent dynamic processes in the developing nervous system can result in windows of exposure that pose higher risks for some life stages. Thus, AOPs will need to incorporate and account for neurodevelopmental-stage-relevant key events.

The goal of this RFA is to seek a better understanding of the pathways that link the key events in AOPs from exposure to adverse outcomes. EPA is particularly interested in funding research projects that focus on endocrine signaling pathways that alter neurodevelopment, but will accept research proposals that address other AOPs. EPA is also interested in tools and methodologies to facilitate the use of AOPs in the development of more efficient screening methods for DNT, and methods for incorporating AOP based screening data in risk assessments. This research will contribute to identifying DNT AOPs for high priority endocrine disruptors, other AOPs critical for DNT, critical exposure routes, and susceptible life stages and populations. This solicitation seeks to support research that will: 1) develop and apply new data to characterize AOPs for DNT outcomes; 2) advance the state-of-knowledge on the key events that link exposure to adverse DNT outcomes; and 3) develop methodologies, tools, and models for incorporating research results into risk assessments.

The specific Strategic Goal and Objective from the EPA’s Strategic Plan that relate to this solicitation are:
Goal 4: Ensuring the Safety of Chemicals and Preventing Pollution, Objective 4.1: Ensure Chemical Safety

More information can be found in EPA’s FY 2011-2015 Strategic Plan

C. Authority and Regulations
The authority for this RFA and resulting awards is contained in the Toxic Substances Control Act, Section 10, 15 U.S.C. 2609, the Federal Insecticide, Fungicide, and Rodenticide Act, Section 20, 7 U.S.C. 136r, the Safe Drinking Water Act, Section 1442, 42 U.S.C. 300j-1, and the Clean Water Act, Section 104, 33 U.S.C. 1254.

For research with an international aspect, the above statutes are supplemented, as appropriate, by the National Environmental Policy Act, Section 102(2)(F).

Note that a project’s focus is to consist of activities within the statutory terms of EPA’s financial assistance authorities; specifically, the statute(s) listed above. Generally, a project must address the causes, effects, extent, prevention, reduction, and elimination of air pollution, water pollution, solid/hazardous waste pollution, toxic substances control, or pesticide control depending on which statute(s) is listed above. These activities should relate to the gathering or transferring of information or advancing the state of knowledge. Proposals should emphasize this “learning” concept, as opposed to “fixing” an environmental problem via a well-established method. Proposals relating to other topics which are sometimes included within the term “environment” such as recreation, conservation, restoration, protection of wildlife habitats, etc., must describe the relationship of these topics to the statutorily required purpose of pollution prevention and/or control.

Applicable regulations include: 40 CFR Part 30 (Uniform Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals, and Other Non-Profit Organizations), 40 CFR Part 31 (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments) and 40 CFR Part 40 (Research and Demonstration Grants). Applicable OMB Circulars include: OMB Circular A-21 (Cost Principles for Educational Institutions) relocated to 2 CFR Part 220, OMB Circular A-87 (Cost Principles for State, Local and Indian Tribal Governments) relocated to 2 CFR Part 225, and OMB Circular A-122 (Cost Principles for Non-Profit Organizations) relocated to 2 CFR Part 230.

D. Specific Research Areas of Interest/Expected Outputs and Outcomes
Note to applicant: The term “output” means an environmental activity or effort, and associated work products, related to a specific environmental goal(s), (e.g., testing a new methodology), that will be produced or developed over a period of time under the agreement. The term “outcome” means the result, effect, or consequence that will occur from the above activit(ies) that is related to an environmental, behavioral, or health-related objective.

The Agency is soliciting research projects that propose innovative approaches to develop AOPs for DNT outcomes. Projects should develop approaches, tools, and models to improve the ability to predict adverse impacts on the developing nervous system from exposure to environmental contaminants. EPA is particularly interested in proposals that incorporate the following:

1. Characterization of AOPs that provide, at a minimum, qualitative correlative links between molecular initiating events, key events, and adverse neurodevelopmental outcomes. EPA encourages the development of AOPs based on causative links between key events (as per modified Bradford-Hill criteria outlined in Boobis et al. 2008).
2. Development of AOP-based models that allow for quantitative prediction of adverse outcomes from molecular initiating or other key events.
3. Development of models that include compensatory mechanisms within the toxicity pathways for the key events are highly encouraged.
4. Development of assays that provide information on the key events of an AOP for DNT in a manner that allows scaling to high-throughput testing. In this case, high-throughput means the ability to collect concentration- or dose-response data for hundreds of chemicals.
5. Develop a methodology to incorporate the research outputs into risk assessments for developmental neurotoxins.

In developing responsive proposals, the following issues should be discussed in terms of determining whether a hypothetical AOP is relevant:

1. Is the adverse outcome of public health or ecological concern?
2. Is the AOP relevant to the species of concern?
3. What key events may be applicable to the AOP?
4. Are methods available to quantitatively measure the key event(s)?
5. Will the AOP be amenable to predictive modeling for risk assessment?

Examples of research responsive to this RFA may include, but are not limited to, characterization of DNT AOPs that result from:

• activation/initiation of endocrine signaling pathways important to nervous system development,
• alterations in pathways regulating the critical cellular events required for normal nervous system development (e.g., neural differentiation, cell migration, synaptogenesis, neural network formation),
• alterations in pathways that control key neuronal/glial cellular processes that may be particularly sensitive in the developing nervous system,
• use of innovative methods and models that incorporate multicellular systems or use human cells (e.g., neural stem cells) to build AOPs.

The application should include a discussion of how the proposed research will identify and/or provide a better understanding of key AOPs that lead to developmental neurotoxicity; advance the state-of-knowledge by linking key events along the continuum from exposure to adverse outcomes; identify widows of susceptibility; and lead to the development of models and/or toxicity testing methodologies that predict the potential for a chemical to adversely impact the developing nervous system. It should also include additional discussion of how these outputs will achieve the goals of faster and more efficient chemical testing, SAR development, or improvement in the reliability of chemical testing to predict adverse effects on humans and other species.

Outputs expected from the research funded under this RFA include reports, presentations, and peer-reviewed journal publications describing advances in the understanding of pathways leading to neurotoxicity, as well as methods and models that allow prediction of temporal and spatial specificity of AOPs, and development of predictive tools and screening methods to evaluate DNT potential in target chemicals. The expected outcome of this research is an increased mechanistic understanding of key events in pathways that lead to DNT.

The use of innovative approaches to develop AOPs is highly encouraged. To the extent practicable, research proposals must embody innovation and sustainability. Innovation for the purposes of this RFA is defined as the process of making changes; a new method, custom or device. Innovative research can take the form of wholly new applications or applications that build on existing knowledge and approaches for new uses. Research proposals must include a discussion on how the proposed research is innovative (see Section IV.B.5.a). The concept of sustainability is based on language in the U.S. National Environmental Policy Act of 1969 (NEPA). This definition is reiterated in Executive Order 13514, Federal Leadership in Environment, Energy, and Economic Performance, stating that the goal of sustainability is to, “create and maintain conditions, under which humans and nature can exist in productive harmony, that permit fulfilling the social, economic, and other requirements of present and future generations.” Research proposals must include a discussion on how the proposed research will seek sustainable solutions that protect the environment and strengthen our communities (see Section IV.B.5.a). ORD will draw from all of the above-mentioned innovation and sustainability definitions in the review/evaluation process of recommending research proposals (see Section V.A).

E. References
[Journals]

1. Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, Villeneuve DL. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 2010;29(3):730-41
2. Sonich-Mullin C, Fielder R, Wiltse J, Baetcke K, Dempsey J, Fenner-Crisp P, Grant D, Hartley M, Knaap A, Kroese D, Mangelsdorf I, Meek E, Rice JM, Younes M. IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis. Regul Toxicol Pharmacol. 2001 34(2):146-52.
3. Boobis AR, Doe JE, Heinrich-Hirsch B, Meek ME, Munn S, Ruchirawat M, Schlatter J, Seed J, Vickers C. IPCS framework for analyzing the relevance of a noncancer mode of action for humans. Crit Rev Toxicol. 2008;38(2):87-96.
4. Crofton KM, Mundy WR, Lein PJ, Bal-Price A, Coecke S, Seiler AE, Knaut H, Buzanska L, Goldberg A. Developmental neurotoxicity testing: recommendations for developing alternative methods for the screening and prioritization of chemicals. ALTEX. 2011;28(1):9-15.

[Reports]

1. OECD (2011) Report of the Workshop on Using Mechanistic Information in Forming Chemical Categories Series on Testing and Assessment No. 138, 8-10 December 2010, Crystal City VA, USA.
2. Coecke S, Goldberg AM, Allen S, Buzanska L, Calamandrei G, Crofton KM, Hareng L, Hartung T, Knaut H, Honegger P, Jacobs M, Lein P, Li A, Mundy W, Owen D, Schneider S, Silbergeld E, Reum T, Trnovec T, Monnet-Tschudi F, Bal-Price A. Workgroup report: incorporating in vitro alternative methods for developmental neurotoxicity into international hazard and risk assessment strategies. Environ Health Perspect. 2007 115:924-31
3. Lein P, Locke P, Goldberg A. Meeting report: alternatives for developmental neurotoxicity testing. Environ Health Perspect. 2007 115:764-8.
4. US EPA (2011) Framework for an EPA Chemical Safety for Sustainability Research Program, June 2011, Office of Research and Development, US Environmental Protection Agency
5. Washington, DC.

F. Special Requirements
Agency policy and ethical considerations prevent EPA technical staff and managers from providing applicants with information that may create an unfair competitive advantage. Consequently, EPA employees will not review, comment, advise, and/or provide technical assistance to applicants preparing applications in response to EPA RFAs. EPA employees cannot endorse any particular application.

Multiple Investigator applications may be submitted as: (1) a single Lead Principal Investigator (PI) application with Co-PI(s) or (2) a Multiple PI application (with a single Contact PI). If you choose to submit a Multiple PI application, you must follow the specific instructions provided in Sections IV. and V. of this RFA. For further information, please see the EPA Implementation Plan for Policy on Multiple Principal Investigators.

This solicitation does not provide the opportunity for the submission of applications for projects that involve human subjects research. Human subjects research supported by the EPA is governed by EPA Regulation 40 CFR Part 26 (Protection of Human Subjects). Applications proposing human subjects research will not be considered for funding and will be deemed ineligible. Human subjects research precluded from this RFA includes projects that collect data from or about humans which meet the regulatory definition of research with human subjects and are thereby subject to the requirements of EPA Regulation 40 CFR Part 26 and EPA Order 1000.17 Change A1. This includes projects conducted under programs that are not considered research for other purposes. For example, some demonstration programs and some public health practice programs may include research activities. Projects that utilize surveys about people or contain identifiable private information also constitutes human subjects research and are not allowable under this solicitation. All applications must include a Non-Human Subjects Research Determination (as described in Section IV.B.5.c), verifying that the proposed research will not involve human subjects.

Groups of two or more eligible applicants may choose to form a consortium and submit a single application for this assistance agreement. The application must identify which organization will be the recipient of the assistance agreement and which organizations(s) will be subawardees of the recipient.

The application shall include a plan (see “Data Plan” in section IV.B.5.d.) to make available to the NCER project officer all data generated (first produced under the award) from observations, analyses, or model development used under an agreement awarded from this RFA. The data must be available in a format and with documentation such that they may be used by others in the scientific community.

II. AWARD INFORMATION

It is anticipated that a total of approximately $4 million will be awarded under this announcement, depending on the availability of funds, quality of applications received, and other applicable considerations. The EPA anticipates funding approximately five awards under this RFA. Requests for amounts in excess of a total of $800,000, including direct and indirect costs, will not be considered. The total project period requested in an application submitted for this RFA may not exceed four years.

The EPA reserves the right to reject all applications and make no awards, or make fewer awards than anticipated, under this RFA. The EPA reserves the right to make additional awards under this announcement, consistent with Agency policy, if additional funding becomes available after the original selections are made. Any additional selections for awards will be made no later than six months after the original selection decisions.

EPA may award both grants and cooperative agreements under this announcement.

Under a grant, EPA scientists and engineers are not permitted to be substantially involved in the execution of the research. However, EPA encourages interaction between its own laboratory scientists and grant Principal Investigators after the award of an EPA grant for the sole purpose of exchanging information in research areas of common interest that may add value to their respective research activities. This interaction must be incidental to achieving the goals of the research under a grant. Interaction that is “incidental” does not involve resource commitments.

Where appropriate, based on consideration of the nature of the proposed project relative to the EPA’s intramural research program and available resources, the EPA may award cooperative agreements under this announcement. When addressing a research question/problem of common interest, collaborations between EPA scientists and the institution’s principal investigators are permitted under a cooperative agreement. These collaborations may include data and information exchange, providing technical input to experimental design and theoretical development, coordinating extramural research with in-house activities, the refinement of valuation endpoints, and joint authorship of journal articles on these activities. Proposals may not identify EPA cooperators or interactions; specific interactions between EPA’s investigators and those of the prospective recipient for cooperative agreements will be negotiated at the time of award.

III. ELIGIBILITY INFORMATION

A. Eligible Applicants
Public nonprofit institutions/organizations (includes public institutions of higher education and hospitals) and private nonprofit institutions/organizations (includes private institutions of higher education and hospitals) located in the U.S., state and local governments, Federally Recognized Indian Tribal Governments, and U.S. territories or possessions are eligible to apply. Profit-making firms are not eligible to receive assistance agreements from the EPA under this program.

Eligible nonprofit organizations include any organizations that meet the definition of nonprofit in OMB Circular A-122, located at 2 CFR Part 230. However, nonprofit organizations described in Section 501(c) (4) of the Internal Revenue Code that lobby are not eligible to apply.

Foreign governments, international organizations, and non-governmental international organizations/institutions are not eligible to apply.

National laboratories funded by Federal Agencies (Federally-Funded Research and Development Centers, “FFRDCs”) may not apply. FFRDC employees may cooperate or collaborate with eligible applicants within the limits imposed by applicable legislation and regulations. They may participate in planning, conducting, and analyzing the research directed by the applicant, but may not direct projects on behalf of the applicant organization. The institution, organization, or governance receiving the award may provide funds through its assistance agreement from the EPA to an FFRDC for research personnel, supplies, equipment, and other expenses directly related to the research. However, salaries for permanent FFRDC employees may not be provided through this mechanism.

Federal Agencies may not apply. Federal employees are not eligible to serve in a principal leadership role on an assistance agreement, and may not receive salaries or augment their Agency’s appropriations in other ways through awards made under this program.

The applicant institution may enter into an agreement with a Federal Agency to purchase or utilize unique supplies or services unavailable in the private sector to the extent authorized by law. Examples are purchase of satellite data, chemical reference standards, analyses, or use of instrumentation or other facilities not available elsewhere. A written justification for federal involvement must be included in the application. In addition, an appropriate form of assurance that documents the commitment, such as a letter of intent from the Federal Agency involved, should be included.

Potential applicants who are uncertain of their eligibility should contact Bronda Harrison (harrison.bronda@epa.gov) in NCER, phone 703-347-8080.

B. Cost-Sharing
Institutional cost-sharing is not required.

C. Other
Applications must substantially comply with the application submission instructions and requirements set forth in Section IV of this announcement or they will be rejected. In addition, where a page limitation is expressed in Section IV with respect to parts of the application, pages in excess of the page limit will not be reviewed. Applications must be submitted through grants.gov or by other authorized alternate means (see Section IV.E. “Submission Instructions and Other Submission Requirements” for further information) on or before the solicitation closing date and time in Section IV of this announcement or they will be returned to the sender without further consideration. Also, applications exceeding the funding limits or project period term described herein will be returned without review. In addition, applications proposing human subjects research will not be considered for funding and will be deemed ineligible. Further, applications that fail to demonstrate a public purpose of support or stimulation (e.g., by proposing research which primarily benefits a Federal program or provides a service for a Federal agency) will not be funded.

Applications deemed ineligible for funding consideration will be notified within fifteen calendar days of the ineligibility determination.

IV. APPLICATION AND SUBMISSION INFORMATION

Formal instructions for submission through Grants.gov follow in Section E.

A. Internet Address to Request Application Package
Use the application package available at Grants.gov (see Section E. “Submission Instructions and Other Submission Requirements”). Note: With the exception of the current and pending support form (available at Forms and Standard Instructions Download Page (https://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms)), all necessary forms are included in the electronic application package.

An email will be sent by NCER to the Lead/Contact PI and the Administrative Contact (see below) to acknowledge receipt of the application and transmit other important information. The email will be sent from receipt.application@epa.gov; emails to this address will not be accepted. If you do not receive an email acknowledgment within 30 days of the submission closing date, immediately inform the Eligibility Contact shown in this solicitation. Failure to do so may result in your application not being reviewed. See Section E. “Submission Instructions and Other Submission Requirements” for additional information regarding the application receipt acknowledgment.

B. Content and Form of Application Submission
The application is made by submitting the materials described below. Applications must contain all information requested and be submitted in the formats described.

 

 

 

 

 

 

 

 

1. Standard Form 424

   The applicant must complete Standard Form 424. Instructions for completion of the SF424 are included with the form. (However, note that EPA requires that the entire requested dollar amount appear on the 424, not simply the proposed first year expenses.) The form must contain the signature of an authorized representative of the applying organization.

   Applicants are required to provide a “Dun and Bradstreet Data Universal Numbering System” (DUNS) number when applying for federal grants or cooperative agreements. Organizations may receive a DUNS number by calling 1-866-705-5711 or by visiting the D&B web site.

   Executive Order 12372, “Intergovernmental Review of Federal Programs,” does not apply to the Office of Research and Development's research and training programs unless EPA has determined that the activities that will be carried out under the applicants' proposal (a) require an Environmental Impact Statement (EIS), or (b) do not require an EIS but will be newly initiated at a particular site and require unusual measures to limit the possibility of adverse exposure or hazard to the general public, or (c) have a unique geographic focus and are directly relevant to the governmental responsibilities of a State or local government within that geographic area.

   If EPA determines that Executive Order 12372 applies to an applicant's proposal, the applicant must follow the procedures in 40 CFR Part 29. The applicant must notify their state's single point of contact (SPOC). To determine whether their state participates in this process, and how to comply, applicants should consult Intergovernmental Review (SPOC List). If an applicant is in a State that does not have a SPOC, or the State has not selected research and development grants for intergovernmental review, the applicant must notify directly affected State, area wide, regional and local entities of its proposal.

   EPA will notify the successful applicant(s) if Executive Order 12372 applies to its proposal prior to award.

2. Key Contacts

   The applicant must complete the “Key Contacts” form found in the Grants.gov application package. An “Additional Key Contacts” form is also available at Forms and Standard Instructions Download Page (https://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms). The Key Contacts form should also be completed for major sub-agreements (i.e., primary investigators). Do not include information for consultants or other contractors. Please make certain that all contact information is accurate.

   For Multiple PI applications: The Additional Key Contacts form must be completed (see Section I.F. for further information). Note: The Contact PI must be affiliated with the institution submitting the application. EPA will direct all communications related to scientific, technical, and budgetary aspects of the project to the Contact PI; however, any information regarding an application will be shared with any PI upon request. The Contact PI is to be listed on the Key Contact Form as the Project Manager/Principal Investigator (the term Project Manager is used on the Grants.gov form, the term Principal Investigator is used on the form located on NCER’s web site). For additional PIs, complete the Major Co-Investigator fields and identify PI status next to the name (e.g., “Name: John Smith, Principal Investigator”).

3. Table of Contents

   Provide a list of the major subdivisions of the application indicating the page number on which each section begins.

4. Abstract (1 page)

   The abstract is a very important document in the review process. Therefore, it is critical that the abstract accurately describes the research being proposed and conveys all the essential elements of the research. Also, the abstracts of applications that receive funding will be posted on the NCER web site.

   The abstract should include the information described below (a-h). Examples of abstracts for current grants may be found on the NCER web site.

   1. Funding Opportunity Title and Number for this proposal.
   2. Project Title: Use the exact title of your project as it appears in the application. The title must be brief yet represent the major thrust of the project. Because the title will be used by those not familiar with the project, use more commonly understood terminology. Do not use general phrases such as “research on.”
   3. Investigators: For applications with multiple investigators, state whether this is a single Lead PI (with co-PIs) or Multiple PI application (see Section I.F.). For Lead PI applications, list the Lead PI, then the name(s) of each co-PI who will significantly contribute to the project. For Multiple PI applications, list the Contact PI, then the name(s) of each additional PI. Provide a web site URL or an email contact address for additional information.
   4. Institution(s): In the same order as the list of investigators, list the name, city and state of each participating university or other applicant institution. The institution applying for assistance must be clearly identified.
   5. Project Period and Location: Show the proposed project beginning and ending dates and the performance sites/geographical location(s) where the work will be conducted.
   6. Project Cost: Show the total funding requested from the EPA (include direct and indirect costs for all years).
   7. Project Summary: Provide three subsections addressing: (1) the objectives of the study (including any hypotheses that will be tested), (2) the experimental approach to be used (a description of the proposed project), and (3) the expected results (outputs/outcomes) of the project and how it addresses the research needs identified in the solicitation, including the estimated improvement in risk assessment or risk management that will result from successful completion of the proposed work.
   8. Supplemental Keywords: Without duplicating terms already used in the text of the abstract, list keywords to assist database searchers in finding your research. A list of suggested keywords may be found at: Forms and Standard Instructions Download Page (https://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms).

5. Research Plan, Quality Assurance Statement, Non-Human Subjects Research Determination, Data Plan, and References

    

    

   1. Research Plan (15 pages)

      Applications should focus on a limited number of research objectives that adequately and clearly demonstrate that they meet the RFA requirements. Explicitly state the main hypotheses that you will investigate, the data you will create or use, the analytical tools you will use to investigate these hypotheses or analyze these data, and the results you expect to achieve. Research methods must be clearly stated so that reviewers can evaluate the appropriateness of your approach and the tools you intend to use. A statement such as: “we will evaluate the data using the usual statistical methods” is not specific enough for peer reviewers.

      This description must not exceed fifteen (15) consecutively numbered (bottom center), 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins. While these guidelines establish the minimum type size requirements, applicants are advised that readability is of paramount importance and should take precedence in selection of an appropriate font for use in the proposal.

      The description must provide the following information:

      1. Objectives: List the objectives of the proposed research and the hypotheses being tested during the project, and briefly state why the intended research is important and how it fulfills the requirements of the solicitation. This section should also include any background or introductory information that would help explain the objectives of the study. If this application is to expand upon research supported by an existing or former assistance agreement awarded under the STAR program, indicate the number of the agreement and provide a brief report of progress and results achieved under it.
      2. Approach/Activities: Outline the research design, methods, and techniques that you intend to use in meeting the objectives stated above.
      3. Innovation: Describe how your project shifts current research or engineering paradigms by using innovative theoretical concepts, approaches or methodologies, instrumentation or interventions applicable to one or more fields of research.
      4. Sustainability: Describe how your project embodies the principles of sustainability and seeks sustainable solutions that protect the environment and strengthen our communities. The Sustainability Primer provides examples of research activities that promote and incorporate sustainability principles.
      5. Expected Results, Benefits, Outputs, and Outcomes: Describe the results you expect to achieve during the project (outputs) and the potential benefits of the results (outcomes). This section should also discuss how the research results will lead to solutions to environmental problems and improve the public’s ability to protect the environment and human health. A clear, concise description will help NCER and peer reviewers understand the merits of the research.
      6. General Project Information: Discuss other information relevant to the potential success of the project. This should include facilities, personnel expertise/experience, project schedules with associated milestones and target dates, proposed management, interactions with other institutions, etc. Applications for multi-investigator projects must identify project management and the functions of each investigator in each team and describe plans to communicate and share data.
      7. Appendices may be included but must remain within the 15-page limit.

   2. Quality Assurance Statement (3 pages)

      For projects involving environmental data collection or processing, modeling, method development, or the development of environmental technology (whether hardware-based or via new techniques), provide a Quality Assurance Statement (QAS) regarding the plans for processes that will be used to ensure that the products of the research satisfy the intended project objectives. Follow the guidelines provided below to ensure that the QAS describes a system that complies with ANSI/ASQC E4, Specifications and Guidelines for Quality Systems for Environmental Data Collection and Environmental Technology Programs. Do not exceed three consecutively numbered, 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins.

      NOTE: If selected for award, applicants will be expected to provide additional quality assurance documentation.

      Address each applicable section below by including the required information, referencing the specific location of the information in the Research Plan, or explaining why the section does not apply to the proposed research. (Not all will apply.)

      1. Identify the individual who will be responsible for the quality assurance (QA) and quality control (QC) aspects of the research along with a brief description of this person’s functions, experience, and authority within the research organization. Describe the organization’s general approach for conducting quality research. (QA is a system of management activities to ensure that a process or item is of the type and quality needed for the project. QC is a system of activities that measures the attributes and performance of a process or item against the standards defined in the project documentation to verify that they meet those stated requirements.)
      2. Discuss project objectives, including quality objectives, any hypotheses to be tested, and the quantitative and/or qualitative procedures that will be used to evaluate the success of the project. Include any plans for peer or other reviews of the study design or analytical methods.
      3. Address each of the following project elements as applicable:
         1. Collection of new/primary data:
            (Note: In this case the word “sample” is intended to mean any finite part of a statistical population whose properties are studied to gain information about the whole. If certain attributes listed below do not apply to the type of samples to be used in your research, simply explain why those attributes are not applicable.)
            1. Discuss the plan for sample collection and analysis. As applicable, include sample type(s), frequency, locations, sample sizes, sampling procedures, and the criteria for determining acceptable data quality (e.g., precision, accuracy, representativeness, completeness, comparability, or data quality objectives).
            2. Describe the procedures for the handling and custody of samples including sample collection, identification, preservation, transportation, and storage, and how the accuracy of test measurements will be verified.
            3. Describe or reference each analytical method to be used, any QA or QC checks or procedures with the associated acceptance criteria, and any procedures that will be used in the calibration and performance evaluation of the analytical instrumentation.
            4. Discuss the procedures for overall data reduction, analysis, and reporting. Include a description of all statistical methods to make inferences and conclusions, acceptable error rates and/or power, and any statistical software to be used.
         2. Use of existing/secondary data (i.e., data previously collected for other purposes or from other sources):
            1. Identify the types of secondary data needed to satisfy the project objectives. Specify requirements relating to the type of data, the age of data, geographical representation, temporal representation, and technological representation, as applicable.
            2. Specify the source(s) of the secondary data and discuss the rationale for selection.
            3. Establish a plan to identify the sources of the secondary data in all deliverables/products.
            4. Specify quality requirements and discuss the appropriateness for their intended use. Accuracy, precision, representativeness, completeness, and comparability need to be addressed, if applicable.
            5. Describe the procedures for determining the quality of the secondary data.
            6. Describe the plan for data management/integrity.
         3. Method development:
            (Note: The data collected for use in method development or evaluation should be described in the QAS as per the guidance in section 3A and/or 3B above.)

             

            Describe the scope and application of the method, any tests (and measurements) to be conducted to support the method development, the type of instrumentation that will be used and any required instrument conditions (e.g., calibration frequency), planned QC checks and associated criteria (e.g., spikes, replicates, blanks), and tests to verify the method’s performance.

         4. Development or refinement of models:
            (Note: The data collected for use in the development or refinement of models should be described in the QAS as per the guidance in section 3A and/or 3B above.)
            1. Discuss the scope and purpose of the model, key assumptions to be made during development/refinement, requirements for code development, and how the model will be documented.
            2. Discuss verification techniques to ensure the source code implements the model correctly.
            3. Discuss validation techniques to determine that the model (assumptions and algorithms) captures the essential phenomena with adequate fidelity
            4. Discuss plans for long-term maintenance of the model and associated data.
         5. Development or operation of environmental technology:
            (Note: The data collected for use in the development or evaluation of the technology should be described in the QAS as per the guidance in section 3A and/or 3B above.)
            1. Describe the overall purpose and anticipated impact of the technology.
            2. Describe the technical and quality specifications of each technology component or process that is to be designed, fabricated, constructed, and/or operated.
            3. Discuss the procedure to be used for documenting and controlling design changes.
            4. Discuss the procedure to be used for documenting the acceptability of processes and components, and discuss how the technology will be benchmarked and its effectiveness determined.
            5. Discuss the documentation requirements for operating instructions/guides for maintenance and use of the system(s) and/or process(s).
      4. Discuss data management activities (e.g., record-keeping procedures, data-handling procedures, and the approach used for data storage and retrieval on electronic media). Include any required computer hardware and software and address any specific performance requirements for the hardware/software configuration used.

   3. Non-Human Subjects Research Determination (1 page)

      This solicitation does not provide the opportunity for the submission of applications for projects that involve human subjects research. All human research studies conducted or supported by EPA are governed by EPA regulations at 40 CFR Part 26 (Protection of Human Subjects). This includes the Basic Federal Policy for the Protection of Human Research Subjects, also known as the Common Rule, at subpart A and additional prohibitions and special protections for pregnant women, nursing women, and children in research conducted or supported by EPA at subparts B, C, and D. Depending upon the type of research being conducted, additional subparts of 40 CFR Part 26 may be relevant. Procedures for the review and oversight of human research subject to 40 CFR Part 26 are also provided in EPA Order 1000.17 Change A1.

      All applications submitted under this solicitation must include a Non-Human Subjects Research Determination, verifying that the proposed research will not involve human subjects (see definitions below).

      Definitions (from 40 CFR Part 26 Subparts A, B, and C)

      • Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.
      • Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes
      • Interaction includes communication or interpersonal contact between investigator and subject.
      • Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).
      • Individually identifiable means the identity of the subject is or may readily be ascertained by the investigator or associated with the information.
      • Research involving the intentional exposure of a human subject means a study of a substance in which the exposure to the substance experienced by a human subject participating in the study would not have occurred but for the human subject’s participation in the study
      • Observational research means any human research that does not meet the definition of research involving intentional exposure of a human subject.

      Non-Human Subjects Research Determination Requirements

      Provide the following statement in your application package verifying that the proposed research will not involve human subjects: “The proposed research does not involve human subjects.” Please use the definitions provided above to ensure consistency in the interpretation of terminology.

   4. Data Plan (2 pages)

      Provide a plan to make all data resulting from an agreement under this RFA available in a format and with documentation/metadata such that they may be used by others in the scientific community. This includes data first produced under the award, i.e., from observations, analyses, or model development collected or used under the agreement. Applicants who plan to develop or enhance databases containing proprietary or restricted information must provide, within the two pages, a strategy to make the data widely available, while protecting privacy or property rights.

   5. References: References cited are in addition to other page limits (e.g. research plan, quality assurance statement, data plan).

6. Budget and Budget Justification

   1. Budget

      Prepare a master budget table using “SF-424A Budget Information for Non-Construction Programs” (aka SF-424A), available in the Grants.gov electronic application package and also at Forms and Standard Instructions Download Page (https://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms). Only complete “Section B-Budget Categories”. Provide the object class budget category (a. - k.) amounts for each budget year under the “Grant Program, Function or Activity” heading. Each column reflects a separate budget year. For example, Column (1) reflects budget year 1. The total budget will be automatically tabulated in column (5).

      If a subaward is included in the application, provide a separate SF-424A and budget justification for the subaward. Include the total amount for the subaward under “Other” in the master SF-424A.

      Applicants may not use subagreements to transfer or delegate their responsibility for successful completion of their EPA assistance agreement. Therefore, EPA expects that subawards or subcontracts should not constitute more than 40% of the total direct cost of the total project budget. If a subaward/subcontract constitutes more than 40% of the total direct cost, additional justification may be required before award, discussing the need for the subaward/subcontract to accomplish the objectives of the research project. Please see Section IV. D below if your organization intends to identify specific contractors, including consultants, and subawardees in your proposal.

      Please note that institutional cost-sharing is not required. However, if voluntary cost-sharing is proposed, a brief statement concerning cost-sharing should be added to the budget justification.

      Please note that when formulating budgets for proposals/applications, applicants must not include management fees or similar charges in excess of the direct costs and indirect costs at the rate approved by the applicant’s cognizant audit agency, or at the rate provided for by the terms of the agreement negotiated with EPA. The term "management fees or similar charges" refers to expenses added to the direct costs in order to a