httk_rfa_061719_ioaa_edits_ncer_ddd_data_highlight_mrh_5_1.pdf

OVERVIEW INFORMATION

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

ADVANCING TOXICOKINETICS FOR EFFICIENT AND

ROBUST CHEMICAL EVALUATIONS

This is the initial announcement of this funding opportunity.

Funding Opportunity Number: EPA-G2019-STAR-D1

Catalog of Federal Domestic Assistance (CFDA) Number: 66.509

Solicitation Opening Date: July 25, 2019 Solicitation Closing Date: September 10, 2019: 11:59:59 pm Eastern Time

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. Grants.gov Submittal Requirements and Limited Exception Procedures B. Application Package Information C. Content and Form of Application Submission

D. Submission Dates and Times E. Funding Restrictions F. Submission Instructions and Other Submission Requirements

V. APPLICATION REVIEW INFORMATION

A. Peer Review B. Relevancy Review C. Past Performance History Review D. Human Subjects Research Statement (HSRS) Review E. Evaluation of the Scientific Data Management Plan F. Funding Decisions G. Additional Provisions for Applicants Incorporated into the Solicitation

VI. AWARD ADMINISTRATION INFORMATION

A. Award Notices B. Disputes C. Administrative and National Policy Requirements

VII. AGENCY CONTACTS

Access Standard STAR Forms (https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms) View research awarded under previous solicitations (https://www.epa.gov/research-grants/research-grant-areas)

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 to advance the development of chemical toxicokinetic tools and approaches for broader applicability during chemical evaluations, with an emphasis on their application within new approach methodology (NAM) frameworks.

Toxicokinetics describes the absorption, distribution, metabolism, and excretion of chemicals and their metabolites by the body, and as such provides a framework for extrapolating in vivo doses of concern from in vitro-derived concentrations that cause perturbations at the cellular or molecular level. The incorporation of new methods, tools and approaches can simultaneously improve predictivity, reduce uncertainty and build confidence in the successful application of such extrapolations.

This solicitation provides the opportunity for the submission of applications for projects that may involve human subjects research. Human subjects research supported by the EPA is governed by EPA Regulation 40 CFR Part 26 (Protection of Human Subjects). This includes the Common Rule at subpart A and prohibitions and additional protections for pregnant women and fetuses, nursing women, and children at subparts B, C, and D. Research meeting the regulatory definition of intentional exposure research found in subpart B is prohibited by that subpart in pregnant women, nursing women, and children. Research meeting the regulatory definition of observational research found in subparts C and D is subject to the additional protections found in those subparts for pregnant women and fetuses (subpart C) and children (subpart D). All https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms https://www.epa.gov/research-grants/research-grant-areas https://www.epa.gov/research-grants/research-grant-areas applications must include a Human Subjects Research Statement (HSRS, as described in Section IV.C.7.c of this solicitation), and if the project involves human subjects research, it will be subject to an additional level of review prior to funding decisions being made as described in Sections V.D and V.E of this solicitation.

Guidance and training for investigators conducting EPA-funded research involving human subjects may be obtained here:

https://www.epa.gov/osa/basic-information-about-human-subjects-research-0 https://www.ecfr.gov/cgi-bin/text-idx?tpl=/ecfrbrowse/Title40/40cfr26_main_02.tpl

The STAR Program’s goal is to stimulate and support scientific and engineering research that advances EPA’s mission to protect human health and the environment. It is a competitive, peer-reviewed, extramural research program that provides access to the nation’s best scientists and engineers in academic and other nonprofit research institutions. STAR funds research on the environmental and public health effects of air quality, environmental changes, water quality and quantity, hazardous waste, toxic substances, and pesticides.

Award Information:

Anticipated Type of Award: Grant 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 three years. Cost-sharing is not required. Applications with budgets exceeding the total award limits will not be considered.

Eligibility Information:

Public and private nonprofit institutions/organizations, public and 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.F. “Submission Instructions and other Submission Requirements”). Note: With the exception of the current and pending support form (available at https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms), all necessary forms are included in the electronic application package. Make sure to include the current and pending support form in your Grants.gov submission.

If your organization is not currently registered with Grants.gov, you need to allow approximately one month to complete the registration process. Please note that the registration process also requires that your organization have a unique entity identifier (e.g., ‘DUNS number’) and a current registration with the System for Award Management (SAM) and the process of obtaining both could take a month or more. Applicants must ensure that all registration requirements are met in order to apply for this opportunity through Grants.gov and should ensure that all such https://www.epa.gov/osa/basic-information-about-human-subjects-research-0 https://www.ecfr.gov/cgi-bin/text-idx?tpl=/ecfrbrowse/Title40/40cfr26_main_02.tpl https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms requirements have been met well in advance of the submission deadline. 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, see Section IV.A below for additional guidance and instructions.

Agency Contacts:

Technical Contact: Barbara Klieforth; phone: 202-564-7223; email: klieforth.barbara@epa.gov Eligibility Contact: Ron Josephson; phone: 202-564-7823; email: josephson.ron@epa.gov Electronic Submissions Contact: Debra M. Jones; phone: 202-564-7839; email:

jones.debram@epa.gov

I. FUNDING OPPORTUNITY DESCRIPTION

A. Introduction

Understanding chemical disposition in the body is very useful in human health assessments where linkages between external exposure, internal dose and likelihood of health effects are important (Andersen, 2003). Toxicokinetics (TK) describes the absorption, distribution, metabolism, and excretion of a chemical and its metabolites by the body. Such information has been used to interpret dose-response relationships obtained from whole animal testing. In addition, when combined with high-throughput in vitro screening data that identify concentrations causing biological perturbations, TK information has led to major advances in the development and acceptance of new approach methodologies (NAMs) for chemical risk assessment (USEPA, 2018). The ability to quantitatively link in vitro-derived biological perturbations to in vivo dose of concern, also known as in vitro-in vivo extrapolation (IVIVE), has demonstrated the value of NAMs in efficiently screening hundreds to thousands of commercial chemicals for which toxicity data had previously been lacking. Despite early gains observed with these various applications of TK knowledge and data, there is a recognized need for incorporation of additional TK assays and inputs to allow greater applicability of TK information across 1) the large chemical space of interest to the EPA; 2) the range of exposure scenarios that are relevant; and 3) the varied populations and lifestages the Agency is tasked with protecting. Moreover, given the vast chemical space of interest and a recognized need to streamline the evaluation process, a focus on increasing throughput is an ongoing and priority need.

EPA recognizes that it is important to engage all available minds to address the environmental challenges the Nation faces. At the same time, EPA seeks to expand the environmental conversation by including members of communities which may have not previously participated in such dialogues to participate in EPA programs. For this reason, EPA strongly encourages all eligible applicants identified in Section III, including minority serving institutions (MSIs), to apply under this opportunity.

mailto:klieforth.barbara@epa.gov mailto:josephson.ron@epa.gov mailto:jones.debram@epa.gov

For purposes of this solicitation, the following are considered MSIs:

1. Historically Black Colleges and Universities, as defined by the Higher Education Act (20 U.S.C. § 1061). A list of these schools can be found at Historically Black Colleges and Universities;

2. Tribal Colleges and Universities (TCUs), as defined by the Higher Education Act (20 U.S.C. § 1059c(b)(3) and (d)(1)). A list of these schools can be found at American Indian Tribally Controlled Colleges and Universities;

3. Hispanic-Serving Institutions (HSIs), as defined by the Higher Education Act (20 U.S.C. § 1101a(a)(5)). A list of these schools can be found at Hispanic-Serving Institutions;

4. Asian American and Native American Pacific Islander-Serving Institutions; (AANAPISIs), as defined by the Higher Education Act (20 U.S.C. § 1059g(a)(2)). A list of these schools can be found at Asian American and Native American Pacific Islander-Serving Institutions; and

5. Predominately Black Institutions (PBIs), as defined by the Higher Education Act of 2008, 20 U.S.C. 1059e(b)(6). A list of these schools can be found at Predominately Black Institutions.

B. Background

In the last ten years, a series of studies have addressed the use of in vitro TK methods developed by the pharmaceutical industry for environmental chemicals (Wetmore et al. 2012, Wetmore et al., 2015, Yoon et al., 2013). At the EPA, these in vitro datasets have been incorporated into an open-source “high-throughput toxicokinetic” (HTTK) R programming language-based modeling package to provide estimates of TK properties and predicted systemic concentrations for chemicals where there are no other data (Pearce et al., 2017). Chemical-specific doses of concern can be predicted from in vitro bioactive concentrations using IVIVE in HTTK. The HTTK tool currently relies on two medium-throughput in vitro assays: The first assay characterizes the amount of chemical that is free (i.e., unbound) in the presence of human plasma protein. The second assay characterizes the rate of metabolism of the parent chemical by incubating a known initial concentration of the chemical with a suspension of human hepatocytes and monitoring the loss of the parent compound over time. Both assays require the development of chemical-specific methods for the determination of chemical concentration in samples, for example, to quantify the disappearance of chemicals due to metabolism. Development of chemical-specific analytical methods is time consuming and not always successful. In addition, there are many aspects of TK not currently probed by these two assays, for example extra-hepatic metabolism, active transport, and the blood-brain barrier. Strategic incorporation of additional TK parameters and/or methodological approaches conducive to use within a NAM framework are likely to improve the predictivity and application of IVIVE approaches.

Besides these in vitro-based approaches, many chemical risk assessments still rely upon animal (e.g., rodent) studies and extrapolation tools for species and dose extrapolations. Consideration of uncertainty and variability with respect to sensitive populations and lifestages is also a high https://sites.ed.gov/whhbcu/one-hundred-and-five-historically-black-colleges-and-universities/ https://sites.ed.gov/whhbcu/one-hundred-and-five-historically-black-colleges-and-universities/ https://sites.ed.gov/whiaiane/tribes-tcus/tribal-colleges-and-universities/ https://sites.ed.gov/whiaiane/tribes-tcus/tribal-colleges-and-universities/ https://www2.ed.gov/about/offices/list/ope/idues/hsi-eligibles-2016.pdf https://www.google.com/maps/d/viewer?mid=1XVkOWKMDORm53pvU0L8EPsrJC94&msa=0&ie=UTF8&t=m&z=3&source=embed&ll=40.58644586187277%2C-148.28228249999984 https://www.google.com/maps/d/viewer?mid=1wlIi3j7gtlNq_w-0NKAb2bF2VmY&ie=UTF&msa=0&ll=37.35160769312532%2C-96.17229800000001&z=4 priority need in these assessments. Thus, measurements of key TK parameters (e.g., blood-brain barrier permeability), even at a nominal (yes/no) or ranking (high/medium/low) level can significantly reduce uncertainty in chemical risk assessment.

This RFA seeks research that develops new and innovative approaches, assays and/or datasets to expand upon currently available chemical TK categories and parameter values for use in chemical evaluations. Development of methods and approaches that increase throughput and predictivity while reducing uncertainty of current IVIVE approaches for ultimate application in a broader NAM framework are a priority need. The proposed research will provide the best available science needed to address these issues. The research will also improve the scientific foundation for environmental policy and decision-making related to chemical exposure and risk.

C. Authority and Regulations

The authority for this RFA and resulting awards is contained in the Toxic Substances Control Act, 15 U.S.C. 2609, Section 10 and the Federal Insecticide, Fungicide, and Rodenticide Act, 7 U.S.C. 136r, Section 20.

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. Further note applications dealing with any aspect of or related to hydraulic fracking will not be funded by EPA through this program.

Additional applicable regulations include: 2 CFR Part 200, 2 CFR Part 1500, and 40 CFR Part 40 (Research and Demonstration Grants).

D. Specific Areas of Interest/Expected Outputs and Outcomes Note to applicant: The term “output” means an environmental activity, effort, and/or associated work products related to an environmental goal or objective, that will be produced or provided over a period of time or by a specified date. The term “outcome” means the result, effect or consequence that will occur from carrying out an environmental program or activity that is related to an environmental or programmatic goal or objective.

The activities to be funded under this announcement support EPA’s FY 2018-22 Strategic Plan (https://www.epa.gov/planandbudget/strategicplan.html). Activities to be funded under this announcement support Goal 3: Rule of Law and Process, Objective 3.3: Prioritize Robust Science, of EPA’s FY 2018-22 Strategic Plan. Awards made under this announcement will further EPA’s priorities supporting robust science for Chemical Safety. All applications must be for projects that support the goal and objective identified above.

https://www.epa.gov/planandbudget/strategicplan.html

EPA also requires that grant applicants adequately describe environmental outputs and outcomes to be achieved under assistance agreements (see EPA Order 5700.7A1, Environmental Results under Assistance Agreements, https://www.epa.gov/grants/epa-order-57007a1-epas-policy-environmental-results-under-epa-assistance-agreements). Applicants must include specific statements describing the environmental results of the proposed project in terms of well-defined outputs and, to the maximum extent practicable, well-defined outcomes that will demonstrate how the project will contribute to the priorities described above.

The research activities to be funded under this announcement are intended to address: 1) gaps in the availability of medium- or high-throughput assays for elucidating chemical toxicokinetics;

and 2) exposure-related factors not currently considered that will reduce the uncertainty in the current approach relevant for a specific exposure scenario, sensitive population or life-stage.

Approaches that can be scaled up to increase throughput or that avoid the need for customization and are widely applicable across many chemical classes are needed more urgently than other comparable but lower-throughput approaches.

The research will support states, municipalities, and tribal governments in their efforts to protect citizens from the effects of chemical pollutants. Any new method should include at a minimum a qualitative evaluation of its predictive ability and domain of applicability.

In developing proposals, applicants should address at least one of the two research areas described below. Proposals may respond to one research area in detail or may integrate work across both areas.

Specific Research Areas:

1) Development and integration of new assays and approaches.

Research in this area should be aimed at developing new in vitro and/or in silico approaches that can be integrated into toxicokinetic screening approaches or rapid assessment methodologies to improve the accuracy of chemical screening, hazard identification or risk assessment. New or refined approaches that generate and make use of experimental in vitro data and address a currently unmet need may include, for example:

a. Assays that reproducibly provide measures for challenging chemicals that are a part of the environmental chemical exposure space (for example, volatile, lipophilic, and/or per- and poly-fluorinated chemicals);

b. Assays that measure TK parameters not currently available via in vitro approaches, that may be of relevance to sensitive populations or lifestages

i. Blood:brain barrier

ii. Extrahepatic metabolism

iii. Microbiome variability

iv. Transporters

v. Placental transfer https://www.epa.gov/grants/epa-order-57007a1-epas-policy-environmental-results-under-epa-assistance-agreements https://www.epa.gov/grants/epa-order-57007a1-epas-policy-environmental-results-under-epa-assistance-agreements

vi. Lactational transfer

vii. Dermal absorption

viii. Better characterization of protein binding

ix. Other in vitro TK assays that may also increase the predictivity of currently employed high throughput IVIVE approaches

c. Approaches that reproducibly characterize metabolite formation that can be used to support of development of in silico tools to predict metabolism and/or metabolic bioactivation

2) High-throughput approaches applicable to multiple chemicals or chemical classes.

Chemical-specific analytical method development is often a significant bottleneck of the currently used TK assays. Research aimed at developing new methods or techniques that are broadly applicable to multiple chemicals/chemical classes may alleviate the low throughput inherent in the conventionally used targeted mass spectrometry method development. Examples could include Nuclear Magnetic Resonance (NMR), radioflow, spectrophotometric, or elemental analysis assays.

Note that the research activities to be funded under this announcement are intended to support development of experimental in vitro toxicokinetic methods and data. Proposals that include the generation of in vitro data in an area that has an unmet need combined with the development of an in silico and/or quantitative structure activity relationship (QSAR) approach from such data are strongly encouraged. However, computational QSAR development should not be the sole focus of a submission for this solicitation.

Expected Outputs and Outcomes Outputs expected include new assays and approaches for toxicokinetic screening approaches or rapid assessment methodologies, high-throughput approaches applicable to multiple chemicals or chemical classes, decision support tools, peer-reviewed journal publications, guidance documents for new approaches, models, and case studies. Desired outputs will include new assays, approaches, and tools to help communities, municipalities, states, regions, and tribal governments address potential human health impacts associated with chemical exposure. With respect to outcomes, this research may enable better planning and decision-making to reduce potential adverse human health and ecological effects.

It is expected that any data generated will be made publicly available and thus be shared in a machine-readable format suitable for incorporation into EPA’s CompTox Dashboard.

To the extent practicable, research applications must embody innovation. 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 applications must include a discussion on how the proposed research is innovative (see Section IV.C.7.a). Reviewers will draw from the above-mentioned innovation definition in the review/evaluation process of research applications (see Section V.A).

E. References

Andersen, M.E. (2003). Toxicokinetic modeling and its applications in chemical risk assessment.

Toxicol Lett 138(1-2):9-27

Pearce, R.G., Setzer, R.W., Strope, C.L., Wambaugh, J.F., and Sipes, N.S. (2017). httk: R Package for High-Throughput Toxicokinetics. J. Stat Softw. 179(4):1-26.

US EPA. (2018). Strategic Plan to Promote the Development and Implementation of Alternative Test Methods within the TSCA Program (EPA Doc # EPA-740-R1-8004), June 22, 2018.

Wetmore, B.A., Wambaugh, J.F., Ferguson, S.S., Sochaski, M.A., Woodrow-Setzer, R., Allen, B., Houck, K.A., Cantwell, K., Judson, R.S., LeCluyse, E., Clewell, H.J. III, Thomas, R.S., Andersen, M.E. (2015). Incorporating High-Throughput Exposure Predictions with Dosimetry- Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing. Toxicol Sci. 2015 Nov;

148(1):121-36. doi: 10.1093/toxsci/kfv171.

Wetmore, B.A., Wambaugh, J.F., Ferguson, S.S., Sochaski, M.A., Rotroff, D.M., Freeman, K., Clewell, H.J. 3rd, Dix, D.J., Andersen, M.E., Houck, K.A., Allen, B., Judson, R.S., Singh, R., Kavlock, R.J., Richard, A.M., and Thomas, R.S. (2012). Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol. Sci. 125(1)157-74.

Yoon, M., Clewell, H.J. III, and Andersen, M.E. (2013). Deriving an explicit hepatic clearance equation accounting for plasma protein binding and hepatocellular uptake. Toxicol. In Vitro, 27(1):11-15.

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 (https://rbm.nih.gov/toolkit.htm).

This solicitation provides the opportunity for the submission of applications for projects that may involve human subjects research. All applications must include a Human Subjects Research Statement (HSRS; described in Section IV.C.7.c of this solicitation). If the project involves human subjects research, it will be subject to an additional level of review prior to funding decisions being made as described in Sections V.D and V.E of this solicitation.

The results of EPA-funded extramural scientific research should be accessible to the public to the greatest extent feasible consistent with applicable law; policies and Orders; the Agency’s mission; resource constraints; and U.S. national, homeland and economic security. This entails maximizing, at no charge, access by the public to peer-reviewed, scientific research journal publications or associated author manuscripts, and their underlying digital research data, created in whole or in part with EPA funds, while protecting personal privacy; recognizing proprietary interests, confidential business information and intellectual property rights; and avoiding significant negative impact on intellectual property rights, innovation and U.S. competitiveness.

Terms and conditions implementing EPA’s data management and public access requirements will be included in the award’s terms and conditions.

When a journal does not submit a journal publication or author manuscript associated with the journal publication directly to the National Institute of Health’s PubMed Central (PMC), recipients are responsible for making the author manuscript accessible to the public at no charge via PMC. The recipient must submit the author manuscript to PMC no later than the end of the embargo period of twelve months after journal publication. PMC then posts the manuscript on its site at the end of the embargo period, so it is accessible to the public.

Recipients are responsible for ensuring that either the journal publication or the author manuscript associated with the journal publication is deposited into PMC, so that the public may read, download, and analyze the research results in digital form. Instructions for depositing author manuscripts associated with journal publications in PMC will be included in the award’s terms and conditions.

Scientific research data underlying a journal publication are to be posted to a publicly accessible data repository by the recipient within 30 days of the date the journal publication or associated author manuscript becomes accessible to the public, whether made accessible by the journal at the time of publication or by PMC following the embargo period, unless (a) the dataset has already been made accessible to the public via public release or another sharing mechanism; or

(b) the research data cannot be released due to one or more constraints, such as requirements to protect personal privacy, proprietary interest, property rights, national security or dual use research of concern. Datasets must contain enough information to allow independent use (understanding, validation and analysis) of the data.

Publication metadata records shall be provided via the National Institute of Health’s Manuscript Submission (NIHMS) when the journal publication or associated author manuscript is submitted to NIHMS. The metadata record for the dataset underlying the journal publication will be made accessible through EPA’s dataset metadata repository within 30 days of the date the journal publication or associated author manuscript becomes accessible to the public, whether made accessible by the journal at the time of publication or by PMC following the embargo period.

Guidance for providing dataset metadata to EPA’s dataset metadata repository will be included https://www.ncbi.nlm.nih.gov/pmc/ https://www.nihms.nih.gov/db/sub.cgi https://edg.epa.gov/metadata/catalog/main/home.page in the award’s terms and conditions.

Applications submitted under this announcement shall include a Scientific Data Management Plan (SDMP) that addresses public access to EPA-funded scientific research data. See the SDMP clause in Section IV for details on the content of an SDMP. Applicants will also be asked to provide past performance information on whether journal publications or associated author manuscripts, and the associated underlying scientific research data and metadata, under prior assistance agreements were made publicly accessible. These items will be evaluated prior to award.

Reasonable, necessary and allocable costs for data management and public access may be included in extramural research applications and detailed in the budget justification described in Section IV.

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 5 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 3 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.

In appropriate circumstances, EPA reserves the right to partially fund applications by funding discrete portions or phases of proposed projects. If EPA decides to partially fund an application, it will do so in a manner that does not prejudice any applicants or affect the basis upon which the application, or portion thereof, was evaluated and selected for award, and therefore maintains the integrity of the competition and selection process.

EPA intends to award only grants 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.

III. ELIGIBILITY INFORMATION

A. Eligible Applicants

Public and private nonprofit institutions/organizations, public and 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 and individuals are not eligible to apply.

Non-profit organization, as defined by 2 CFR Part 200, means any corporation, trust, association, cooperative or other organization that: (1) is operated primarily for scientific, educational, service, charitable or similar purposes in the public interest; (2) is not organized primarily for profit; and (3) uses its net proceeds to maintain, improve and/or expand its operations. Note that 2 CFR Part 200 specifically excludes the following types of organizations from the definition of “non-profit organization” because they are separately defined in the regulation: (i) institutions of higher education; and (ii) state, local and federally-recognized Indian tribal governments. While not considered to be a “non-profit organization(s)” as defined by 2 CFR Part 200, Institutions of Higher Education and state, local and federally-recognized Indian tribal governments are, nevertheless, eligible to submit applications under this RFA. Hospitals operated by state, tribal, or local governments or that meet the definition of nonprofit at 2 CFR 200.70 are also eligible to apply. For-profit colleges, universities, trade schools, and hospitals are ineligible. 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. Federal employees may not receive salaries or augment their Agency’s appropriations through awards made under this program unless authorized by law to receive such funding.

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 Ron Josephson in the Office of Research and Development (ORD), phone: 202-564-7823, email:

josephson.ron@epa.gov.

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. In addition, applications must be submitted through Grants.gov as stated in Section IV of this announcement (except in the limited circumstances where another mode of submission is specifically allowed for as explained in Section IV) on or before the application submission deadline published in Section IV of this announcement. Applicants are responsible for following the submission instructions in Section IV of this announcement (see Section IV.F. “Submission Instructions and Other Submission Requirements” for further information) to ensure that their application is submitted timely.

Applications submitted after the submission deadline will be considered late and deemed ineligible without further consideration unless the applicant can clearly demonstrate that it was late due to EPA mishandling or because of technical problems associated with Grants.gov or relevant SAM.gov system issues. An applicant’s failure to timely submit their application through Grants.gov because they did not timely or properly register in SAM.gov or Grants.gov will not be considered an acceptable reason to consider a late submission.

Also, applications exceeding the funding limits or project period term described herein will be rejected without review. 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

Additional provisions that apply to this solicitation and/or awards made under this solicitation, including but not limited to those related to confidential business information, mailto:josephson.ron@epa.gov https://www.grants.gov/ https://www.grants.gov/ http://www.sam.gov/ https://www.grants.gov/ http://www.sam.gov/ https://www.grants.gov/ contracts and subawards under grants, and proposal assistance and communications, can be found at https://www2.epa.gov/grants/epa-solicitation-clauses.

These, and the other provisions that can be found at the website link, are important, and applicants must review them when preparing applications for this solicitation. If you are unable to access these provisions electronically at the website above, please communicate with the EPA contact listed in this solicitation to obtain the provisions.

Formal instructions for submission through Grants.gov are in Section F.

A. Grants.gov Submittal Requirements and Limited Exception Procedures Applicants, except as noted below, must apply electronically through Grants.gov under this funding opportunity based on the grants.gov instructions in this announcement. If an applicant does not have the technical capability to apply electronically through grants.gov because of limited or no internet access which prevents them from being able to upload the required application materials to Grants.gov, the applicant must contact OMS-ARM- OGDWaivers@epa.gov or the address listed below in writing (e.g., by hard copy, email) at least 15 calendar days prior to the submission deadline under this announcement to request approval to submit their application materials through an alternate method.

Mailing Address:

OGD Waivers c/o Jessica Durand USEPA Headquarters William Jefferson Clinton Building 1200 Pennsylvania Ave., N. W.

Mail Code: 3903R Washington, DC 20460

Courier Address:

OGD Waivers c/o Jessica Durand Ronald Reagan Building 1300 Pennsylvania Ave., N.W.

Rm # 51278 Washington, DC 20004

In the request, the applicant must include the following information:

Funding Opportunity Number (FON) Organization Name and Unique Entity Identifier (e.g., DUNS) Organization’s Contact Information (email address and phone number) Explanation of how they lack the technical capability to apply electronically through https://www2.epa.gov/grants/epa-solicitation-clauses https://www.grants.gov/ https://www.grants.gov/ mailto:OMS-ARM-OGDWaivers@epa.gov mailto:OMS-ARM-OGDWaivers@epa.gov

Grants.gov because of: 1) limited internet access or 2) no internet access which prevents them from being able to upload the required application materials through Grants.gov.

EPA will only consider alternate submission exception requests based on the two reasons stated above and will timely respond to the request -- all other requests will be denied. If an alternate submission method is approved, the applicant will receive documentation of this approval and further instructions on how to apply under this announcement. Applicants will be required to submit the documentation of approval with any initial application submitted under the alternative method. In addition, any submittal through an alternative method must comply with all applicable requirements and deadlines in the announcement including the submission deadline and requirements regarding application content and page limits (although the documentation of approval of an alternate submission method will not count against any page limits).

If an exception is granted, it is valid for submissions to EPA for the remainder of the entire calendar year in which the exception was approved and can be used to justify alternative submission methods for application submissions made through December 31 of the calendar year in which the exception was approved (e.g., if the exception was approved on March 1, 2019, it is valid for any competitive or non-competitive application submission to EPA through December 31, 2019). Applicants need only request an exception once in a calendar year and all exceptions will expire on December 31 of that calendar year. Applicants must request a new exception from required electronic submission through Grants.gov for submissions for any succeeding calendar year. For example, if there is a competitive opportunity issued on December 1, 2018 with a submission deadline of January 15, 2019, the applicant would need a new exception to submit through alternative methods beginning January 1, 2019.

Please note that the process described in this section is only for requesting alternate submission methods. All other inquiries about this announcement must be directed to the Agency Contact listed in Section VII of this announcement. Queries or requests submitted to the email address identified above for any reason other than to request an alternate submission method will not be acknowledged or answered.

B. Application Package Information

Use the application package available at Grants.gov (see Section IV.F. “Submission Instructions and Other Submission Requirements”). Note: With the exception of the current and pending support form (available at https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms), all necessary forms are included in the electronic application package. Make sure to include the current and pending support form in your Grants.gov submission.

An email will be sent by ORD 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 acknowledgement within 10 calendar days of the submission closing date, immediately inform the Electronic Submissions Contact shown in this solicitation.

Failure to do so may result in your application not being reviewed. See Section IV.F.

“Submission Instructions and Other Submission Requirements” for additional information regarding the application receipt acknowledgment.

C. 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 SF424, 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 unique entity identifier (e.g., ‘DUNS number’) when applying for federal grants or cooperative agreements. Organizations may receive a unique entity identifier, at no cost, by calling the dedicated toll-free request line at 1-866-705-5711, or visiting the website at: https://www.dnb.com.

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 proposed application (a) requires an Environmental Impact Statement (EIS), or (b) does 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) has 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 a proposed application, 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 https://www.whitehouse.gov/omb/management/office-federal-financial-management/. 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 application.

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

2. Key Contacts mailto:receipt.application@epa.gov https://www.dnb.com/ https://www.whitehouse.gov/omb/management/office-federal-financial-management/ https://www.whitehouse.gov/omb/management/office-federal-financial-management/

The applicant must complete the “Key Contacts” form found in the Grants.gov application package. An “Additional Key Contacts” form is also available at https://www.epa.gov/research-grants/research-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 at https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms). 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. SF-424B, Assurances – Non-Construction Programs (available at https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms).

4. EPA Form 4700-4, Preaward Compliance Review Report for All Applicants and Recipients Requesting EPA Financial Assistance (available at https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms).

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

6. 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 EPA’s Research Grants website.

The abstract should include the information described below (a-h). Examples of abstracts for current grants may be found on EPA’s Research Grants website.

a. Funding Opportunity Title and Number for this application.

https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms https://www.epa.gov/research-grants

b. 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.”

c. 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 website URL or an email contact address for additional information.

d. 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.

e. Project…