Grantee Research Project Results

RFA-ES-06-008: Manufactured Nanomaterials: Physico-chemical Principles of Biocompatibility and Toxicity (R01)

Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)
Center for Disease Control and Prevention (http://www.cdc.gov)
US Environmental Protection Agency (https://www.epa.gov)

Components of Participating Organizations
National Institute of Environmental Health Sciences (NIEHS) (http://www.niehs.nih.gov)
National Cancer Institute (NCI) (http://www.cancer.gov)
National Institute of Occupational Safety and Health (http://www.cdc.gov/niosh)
US EPA Office of Research and Development, National Center for Environmental Research (https://www.epa.gov/research-grants)
National Eye Institute (NEI) (http://www.nei.nih.gov/)
National Human Genome Research Institute (NHGRI) ( http://www.genome.gov/)
National Institute of General Medical Sciences (NIGMS) (http://www.nigms.nih.gov/)
National Institute of Dental and Craniofacial Research (NIDCR) (http://www.nidcr.nih.gov/)

Title: Manufactured Nanomaterials: Physico-chemical Principles of Biocompatibility and Toxicity (R01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-ES-06-008

Catalog of Federal Domestic Assistance Number(s)
93.114, 93.393, 93.399, 93.867, 93.172, 93.859 , 93.121, 66.509, 93.262

Key Dates
Release Date: September 29, 2006
Letters of Intent Receipt Date(s): December 13, 2006
Application Receipt Date(s): January 12, 2007
Peer Review Date(s): April-May, 2007
Council Review Date(s): September, 2007
Earliest Anticipated Start Date: September, 2007
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: January 13, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

The primary goal of this research initiative is to encourage research on the physico-chemical interaction of manufactured nanoscale materials with mammalian systems.
A project within the research plan that is designed and implemented by investigators from the United States and the European Union is encouraged but not required.
Applicants will use the R01 mechanism.
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of the awards will also vary. The total amount awarded and the number of awards will depend on the number, quality, duration, and costs of the applications received.
Funding agencies:
NIH supports research to meet its mission to reduce the burden of human illness and dysfunction from environmental causes by defining how environmental exposures affect an individual's health status. Information resulting from this solicitation will be used to determine the characteristics of nanomaterial biocompatibility and toxicity. NIH is interested in funding research that explores dose metrics and routes of nanomaterial exposure, and the molecular, cellular, and organ system response to exposure.
NIOSH supports research to identify and investigate the relationships between hazardous working conditions and associated occupational diseases and injuries; to develop more sensitive means of evaluating hazards at work sites, as well as methods for measuring early markers of adverse health effects and injuries; to develop new protective equipment, engineering control technology, and work practices to reduce the risks of occupational hazards; and to evaluate the technical feasibility or application of a new or improved occupational safety and health procedure, method, technique, or system.
EPA supports research to meet its mission of protecting human health and the environment. Research solicited under this funding announcement will be used by the engineering and scientific community in risk assessment, specifically in hazard identification and exposure assessment. EPA is interested in funding research on the possible risks and exposure routes of newly produced chemicals and materials at the nanoscale.
Eligible organizations include domestic, for profit and non-profit, public and private institutions such as universities, colleges, hospitals, laboratories, faith based or community based organizations, units of State/Local government, Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); and Indian/Native American Tribally Designated Organization, and eligible agencies of the federal government. Applications from foreign organizations will not be accepted.
Eligible principal investigators include those with the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support
Applicants may submit more than one application, provided they are scientifically distinct. See Section IV.1 for application materials.
Telecommunications for the hearing impaired is available at: TTY 301-451-0088

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

Section II. Award Information
  1. Mechanism(s) of Support
  2. Funds Available

Section III. Eligibility Information
  1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
  2.Cost Sharing or Matching
  3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
  1. Address to Request Application Information
  2. Content and Form of Application Submission
  3. Submission Dates and Times
    A. Receipt and Review and Anticipated Start Dates
      1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
  4. Intergovernmental Review
  5. Funding Restrictions
  6. Other Submission Requirements

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Background

Nanoscale science and technology involve the imaging, measuring, modeling and manipulation of matter on the scale of 1 to 100 nanometers - a scale at which novel physical, chemical and biological properties enable novel applications. Quantum properties strongly influence the physico-chemical properties of nanoscale materials, conferring electrical, optical and magnetic properties not present in corresponding materials at a larger scale. A large surface area to mass ratio, crystalline structure, shape, surface chemistry and potential for self assembly make nanoscale materials useful in industry and medicine. The nanotechnology industry is projected to exceed $1 trillion by 2015.

This projected increase in demand and production of nanoscale materials will be accompanied by an increased opportunity for population-based exposures. The initial population-based exposures are most likely to occur in the US workforce engaged in manufacture and production of nanoscale materials; the size of this workforce is currently not known. Nanoscale materials in industrial settings and in consumer products represent the categories of materials most likely to result in unintentional, population-based exposures and least likely to undergo rigorous safety testing prior to release. These materials, designated in this document as manufactured nanoscale materials, include nanoparticles, nanotubes and wires, fullerenes, dendrimers, quantum dots and metal oxides. Current studies indicate that the biological consequences of nanomaterials exposure—biocompatibility or toxicity—are material and formulation specific. Biological consequences include oxidative stress and inflammation, impaired pulmonary clearance, cardiac compromise, a skewed immune response, and development of pulmonary fibrosis and foreign body granulomas. Other nanomaterials, in particular several with highly derivatized surfaces, are compatible with biological systems and permissive for cell growth and differentiation. Research is needed to understand the fundamental properties of nanoscale materials that support toxicity and biocompatibility. The relationship of dose as a mass measurement to surface area and particle number, the routes of exposure, and the mechanisms of cellular uptake and response, including transport and sequestration in the body, biotransformation and biopersistence are critical to the development of nanoscale materials with a high biocompatibility / toxicity ratio.

Purpose

The objective of this Funding Opportunity Announcement is to support research that will identify the physico-chemical properties of manufactured nanoscale materials that support biocompatibility and thus protect public health. This knowledge will be directly applicable to responsible development of manufactured nanoscale materials for industry and consumer products as well as medical devices and therapeutics.

Research Program

Research programs that explore the systemic, cellular and molecular responses to manufactured nanoscale materials in vivo, or in vitro studies based on physiology or pathobiology previously identified through in vivo studies, are considered responsive to this Announcement. Because the physico-chemical properties of nanoscale materials may change during preparation, administration, or over time in the experimental model, the experimental design must include evaluation of the physical and chemical characteristics of nanoscale materials at multiple points in the exposure paradigm and link these measurements to biological endpoints. Physical and chemical characteristics that should be considered include elemental composition, particle number, particle size distribution, particle shape, surface area of the primary particle and agglomerated material, intracellular or in vivo agglomeration/de-agglomeration status, charge and chemistry. Interdisciplinary research teams that combine expertise in the physical and biological sciences and state-of-the-art methodologies including “omics” and imaging technologies are strongly encouraged.

NIH, EPA and NIOSH support research on the biological consequences of exposure of manufactured nanoscale materials, however applications responsive to the NIOSH mission must address occupationally-relevant nanoscale materials and health effects.

Examples of research on manufactured nanoscale materials include, but are not limited to:

Comparison of routes of exposure (respiratory, dermal, gastric, ocular) and subsequent systemic distribution of nanoscale materials for single nanomaterial exposure, mixed exposure and multiple exposure routes
Evaluation of dosemetrics, that is, identification of critical physico-chemical parameters of nanomaterials that correlate with the magnitude of the biological response, e.g., surface area, particle size distribution, surface chemistry, in vivo and intracellular agglomeration/de-agglomeration status, maintenance of quantum properties in agglomerated/de-agglomerated material
Mechanisms of cellular uptake, subcellular localization, and cellular retention
Determination of the relationship between magnitude of exposure and cellular/organ system uptake; biotransformation and bioaccumulation of nanomaterials
Molecular, cellular and organ system compensatory mechanisms or toxicological responses following acute or chronic nanoscale materials exposure
Determinants of biological compatibility or toxicity, such as surface composition and chemistry, size and shape (including primary particle vs agglomerate), biological transformation of nanoscale materials
Identification of susceptible populations and differences in the molecular, cellular and organ system compensatory mechanisms or toxicological responses in these populations
Development of models to evaluate and predict toxicity and biomarkers of exposure and biological response

Exclusions

Nanomaterials, devices and products with medical application and whose safety testing falls within the Food and Drug Administration (FDA) purview are excluded from this RFA unless direct applicability to industrial and consumer applications can be demonstrated.

Ambient ultrafine particulates that occur as byproducts in industrial processes, e.g., combustion byproducts, are excluded.

Because nanotechnology research often requires highly sophisticated instrumentation and facilities, the nanotechnology centers supported by the Department of Energy (DOE) and the National Science Foundation (NSF) represent opportunities to leverage research through collaboration. Collaboration with these centers, while it may enhance the research design, is NOT required for submission of an application.

Although expertise varies by Center, DOE laboratories provide support for materials science, physics, chemistry, biology, and molecular biology. The Centers may contain some combination of state-of-the-art clean rooms, general laboratories, wet and dry laboratories for sample preparation, fabrication and analysis, and equipment to synthesize, manipulate, and characterize nanoscale materials and structures. The applicant is responsible for contacting the facilities to discuss potential collaboration. Examples of these Centers include:

DOE Nanoscale Science Research Centers (http://www.er.doe.gov/production/bes/BESfacilities.htm#NSRC)

The Center for Nanophase Materials Sciences (CNMS) at Oak Ridge National Laboratory is a research center and user facility that focuses on nano-dimensioned soft materials, complex nanophase materials systems, and the crosscutting areas of interfaces and reduced dimensionality that become scientifically critical on the nanoscale. For more information, contact: CNMS User Coordinator at 865.576.2858

• The Molecular Foundry at Lawrence Berkeley National Laboratory (LBNL) uses existing LBNL facilities such as the Advanced Light Source, the National Center for Electron Microscopy, and the National Energy Research Scientific Computing Center. Photo, uv, and e-beam lithography equipment and advanced preparative and analytical chromatographic equipment are also available. For more information, contact: Molecular Foundry Administrator at 510.486.7632

• The Center for Integrated Nanotechnologies (CINT) focuses on exploring the path from scientific discovery to the integration of nanostructures into the micro- and macro-worlds. CINT focus areas are nanophotonics and nanoelectronics, complex functional nanomaterials, nanomechanics, and the nanoscale/bio/microscale interfaces. CINT For more information, contact: CINT Outreach Coordinator at 505.844.5457

• The Center for Functional Nanomaterials at Brookhaven National Laboratory will have as its focus understanding the chemical and physical response of nanomaterials to make functional materials such as sensors, activators, and energy-conversion devices. For more information, contact: CFN User Coordinator at 631.344.5763

• The Center for Nanoscale Materials at Argonne National Laboratory conducts research in advanced magnetic materials, complex oxides, nanophotonics, and bio-inorganic hybrids. The facility uses existing facilities such as the Advanced Photon Source, the Intense Pulsed Neutron Source, and the Electron Microscopy Center. For more information, contact: CNM User Administrator at 630.252.2725

The NSF has established numerous Materials Research Science and Engineering Centers (MRSECs) at academic institutions across the country. To investigate the potential for collaboration with these facilities, please use the weblink http://www.nsf.gov/news/news_summ.jsp?cntn_id=104462.

Optional Research Project

Because nanotechnology offers significant improvements in industrial materials and devices to nations around the world, international collaborations represent a cost effective mechanism to maximize the nanomaterials health and safety research investment. To support this goal, applicants may choose to submit a collaborative supplemental project that is designed and implemented by the Principle Investigator and an international co-investigator. This collaborative research project should be integrated with the overall research plan, and the description of the project should follow the Research Methods and Design Section of the main proposal. This section should be clearly titled Optional Research Project and should not exceed 5 pages. An additional budget of $50,000 may be requested and should be detailed on a separate budget page entitled Budget for the Optional Research Project in the budget section of the application.

These collaborative projects are encouraged, but NOT required, and will be evaluated according to the NIH review criteria (Section V.2) and scored separately from the main body of the research plan.

For EPA:

Specific Research Areas of Interest/Expected Outputs and Outcomes.

[Note to applicants: 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].

Expected outputs of this research would include progress review workshops geared towards increasing the collaboration and coordination of toxicological research on manufactured nanomaterials on both national and international levels and publication of workshop proceedings. Examples of outcomes of this research would include providing researchers with critical information concerning the potential effect upon living organisms of manufactured nanomaterials and enhanced environmental protection through the increased availability of important toxicity data on these materials. Relevant goals of this research would include providing scientific information concerning the potential effects of engineered nanomaterials on the biosystem that may initially impact one or more organisms and improved data on biotransformation, bioaccumulation and bioavailability capacities.

Quality Assurance Statement

Quality Assurance Statements will be necessary for analytical, quantitative measurements in support of the applicant's projects.

EPA regulations as stated in 40CFR30.54 require the inclusion of a Quality Assurance Narrative Statement (QANS, OMB # 2080-0033, approved 8/14/97) for any project application involving data collection or processing, environmental measurements, and/or modeling. The QANS provides information on how quality processes or products will be assured. Please visit the EPA web page for additional guidance on QA statements at: https://www2.epa.gov/research-grants/guidance-frequent-questions.

While applications to NIEHS/NIH cannot be considered incomplete without this statement, EPA cannot fund any application without a reviewed QANS; therefore it is requested that the QANS be included with all applications. For awards that involve environmentally related measurements or data generation, a quality system that complies with the requirements of ANSI/ASQC E4, "Specifications and Guidelines for Quality Systems for Environmental Data Collection and Environmental Technology Programs," must be in place. The Quality Assurance Statement should not exceed two pages. This Statement should, for each item listed below, present the required information, reference the specific page and paragraph number of the project description containing the information, or provide a justification as to why the item does not apply to the proposed research.

1. Discuss the activities to be performed or hypothesis to be tested and criteria for determining acceptable data quality. (Note: Such criteria may be expressed in terms of precision, accuracy, representativeness, completeness, and comparability or in terms of data quality objectives or acceptance criteria. Furthermore, these criteria must also be applied to determine the acceptability of existing or secondary data to be used in the project. In this context secondary data may be defined as data collected for other

purposes or from other sources, including the literature, compilations from computerized data bases, or results from mathematical models of environmental processes and conditions.)

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

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

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

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

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

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

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the R01 award mechanism.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement: http://grants.nih.gov/grants/policy/policy.htm#gps). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium F&A costs), use the Modular Budget Component provided in the SF424 (R&R) Application Package and Instructions Guide (see specifically Section 5.4). Otherwise, follow the instructions for non-modular research grant applications.

2. Funds Available

NIH and NIOSH:

NIEHS anticipates awarding $2 million dollars to fund 4-5 awards in Fiscal Year 2007 from this one solicitation. NIOSH, NCI, and NEI anticipate awarding $0.5M each and NHGRI and NIDCR $0.3M each.
The applicant may request a budget for direct costs up to $300,000 for the first year. The budgets for each subsequent year may not exceed an escalation of three percent on recurring direct costs.
The budget should include funds for an annual grantee meeting.
Applicants may request up to four years of support.
Facilities and Administrative (F&A) costs incurred by including third party consortia or subcontracts in the application are not included in the direct cost limitation; see NOT-OD-05-004. the anticipated start date is July, 2007 and periods of performance for new awards from 2006 – 2011
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

EPA:

EPA intends to commit up to $0.5 million annually for a total of 1 award. The total project period for an application submitted in response to this RFA may not exceed 4 years. Awards are contingent upon availability of funds and receipt of a sufficient number of meritorious applications. The EPA reserves the right to make additional awards under this RFA if additional funding becomes available. Any additional selections for awards will be made no later than 4 months after the original selection decisions. EPA intends to fund grants or cooperative agreements under this announcement. Agency scientists and engineers will not be substantially involved in grants receiving EPA funding.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

For NIH and NIOSH:

You may submit (an) application(s) if your organization has any of the following characteristics:

For-profit organizations
Non-profit organizations
Public or private institutions, such as universities, colleges, hospitals, and laboratories
Units of State government
Units of local government
Eligible agencies of the Federal government
Domestic Institutions
Faith-based or community-based organizations
Indian/Native American Tribal Government (Federally Recognized)
Indian/Native American Tribal Government (Other than Federally Recognized)
Indian/Native American Tribally Designated Organization

Applications from foreign institutions will not be accepted, however, international co-investigators are required for the optional international collaborative project.

For EPA:

Eligible institutions include 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. However, nonprofit organizations described in Section 501(c) (4) of the Internal Revenue Code that lobby 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. Examples are purchase of satellite data, census data tapes, 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 Tom Barnwell in NCER, phone (202) 343-9862, email: barnwell.thomas@epa.gov.

1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Multiple Principal Investigators are not permitted on this FOA.

2. Cost Sharing or Matching

Cost sharing is not required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Relevance to the goals of the RFA described under Section I, Research Objectives, will be considered in accepting applications for review. Applications that are not relevant to these goals will not be reviewed. Applicants may submit more than one application under this announcement provided they are scientifically distinct.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-0088.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date(s): December 13, 2006
Application Receipt Date(s): January 12, 2007
Peer Review Date: April-May, 2007
Council Review Date: September, 2007
Earliest Anticipated Start Date: September, 2007

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the Principal Investigator
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Sally E. Eckert-Tilotta, Ph.D.
Scientific Review Administrator
National Institute of Environmental Health Sciences
79 TW Alexander Drive
Building 4401, Room 3173
Research Triangle Park, NC 27709-2233
Telephone: (919) 541-1446
FAX: 919-541-2503
Email: eckertt1@niehs.nih.gov

3.B. Sending an Application to the NIH
Applications must be prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Sally E. Eckert-Tilotta, Ph.D.
Scientific Review Administrator
National Institute of Environmental Health Sciences
79 TW Alexander Drive
Building 4401, Room 3173
Research Triangle Park, NC 27709-2233
Telephone: (919) 541-1446
FAX: 919-541-2503
Email: eckertt1@niehs.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by NIEHS. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/policy.htm).

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

For EPA Awards:

The funding mechanism for all awards issued under STAR solicitations will consist of assistance agreements from the EPA. All award decisions are subject to the availability of funds. In accordance with the Federal Grant and Cooperative Agreement Act, 31 U.S.C. 6301 et seq., the primary purpose of an assistance agreement is to accomplish a public purpose of support or stimulation authorized by federal statute, rather than acquisition for the direct benefit or use of the Agency. In issuing a grant, the EPA anticipates that there will be no substantial EPA involvement in the design, implementation, or conduct of the research. However, the EPA will monitor research progress through annual reports provided by grantees and other contacts, including site visits, with the Principal Investigator.

If you wish to submit applications for more than one STAR funding opportunity you must ensure that the research proposed in each application is significantly different from any other that has been submitted to the EPA or from any other financial assistance you are currently receiving from the EPA or other federal government agency.

Collaborative applications involving more than one institution must be submitted as a single administrative package from one of the institutions involved.

Any contracts for services or products funded with EPA financial assistance must be awarded under the competitive procurement procedures of 40 CFR Part 30 and/or Part 31. Moreover, naming a specific contractor in the application does not relieve the applicant of its obligations to comply with competitive procurement requirements. Also, the regulations contain limitations on consultant compensation.

6. Other Submission Requirements

Specific Instructions for Modular Grant applications. Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Plan for Sharing Research Data

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review
Availability of funds
Relevance of program priorities

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIEHS in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
Receive a written critique.
Receive a second level of review that will be conducted by the appropriate national advisory council or board (National Advisory Environmental Health Sciences Council; National Cancer Advisory Board; for NIOSH, NIOSH Secondary Review Committee; and the EPA, Program Review) for the participating funding partners.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem or research needs in the topic area? If the aims of the application are achieved, how will scientific knowledge be advanced? What are the projected benefits of the proposed activity to society, such as improving the environment or health? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the results be disseminated broadly to enhance scientific and technological understanding?

Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Are there specific plans within the experimental design for physico-chemical characterization of nanomaterials both pre and post-administration? Is the approach technically defensible and achievable in the project period? Is there an adequate plan to track and assess progress toward meeting the goals as described in the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Does the project challenge existing paradigms; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Is the project original and innovative? Is the project likely to identify fundamental physico-chemical principles of industrial and consumer nanomaterials and relate these principles to the biological response?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the applicant or a co-investigator have the ability to perform physico-chemical characterization of the nanomaterials? Does the investigative team bring complementary and integrated expertise to the project? Have they demonstrated an understanding of the pertinent literature? Have the key personnel committed adequate time to the project?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Are the proposed studies supported by adequate facilities and equipment, or are there any deficiencies that threaten the success of the project? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements?

Quality Assurance Statement: Are the proposed Quality Assurance procedures well described and adequate to ensure integrity of the data generated?

Optional Project Review

The optional project will be reviewed and scored separately using the same criteria described above with the following addition:

Integration of Optional Project: Is the collaborative project well integrated with, but not duplicative of, the overall research plan of the application? For example, is it a natural extension of the scope of the main project, does it fill a particular deficiency in expertise or capability, or does it take advantage of a unique opportunity? Does the international collaborator make a meaningful contribution to the project?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. Input on the appropriateness of requested instrumentation is helpful. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

For EPA:

After the peer review, potential EPA applicants who received scores of excellent (NIH scores 1.0 – 1.4) or very good (NIH scores 1.5 – 1.9) as a result of the peer review process will be asked to provide additional information for the programmatic review pertaining to the proposed Lead Principal Investigator's (PI) "Past Performance and Reporting History." The applicant must provide the EPA Project Officer with information on the proposed Lead PI's past performance and reporting history under prior Federal agency assistance agreements in terms of: (i) the level of success in performing each agreement, and (ii) how progress towards achieving the results intended under each agreement was reported. This information is required only for the proposed Lead PI's performance under Federal assistance agreements initiated within the last three years that were similar in size and scope to the proposed project.

The specific information required for each agreement is shown below, and must be provided within two weeks of EPA's request. A maximum of three pages will be permitted for the response; excess pages will not be reviewed. Note: If no prior past performance information and/or reporting history exists, you will be asked to so state.

1. Name of Granting Agency.

2. Grant/Cooperative agreement number.

3. Grant/Cooperative agreement title.

4. Brief description of the grant/cooperative agreement.

5. A description of how the agreement is similar in size and scope to the proposed project and whether or not it was successfully performed; if not successfully performed, provide an explanation.

6. Information relating to the proposed Lead PI's past performance in reporting on progress towards achieving the expected results (outputs/outcomes) under the agreement. Include the history of submitting timely progress/final technical reports, describe how progress towards achieving the expected results was reported/documented, and if such progress was not being made, provide an explanation of whether, and how, this was reported.

7. Total (all years) grant/cooperative agreement dollar value.

8. Project period.

9. Technical contact (project officer), telephone number, and E-mail address (if available).

Final funding decisions are made by the NCER Director based on the results of the peer review and internal programmatic review including past performance considerations. In addition, in making the final funding decisions, the NCER Director may also consider program balance, available funds, and the Congressionally-mandated Experimental Program to Stimulate Competitive Research (EPSCOR) (see https://www.epa.gov/research-grants/). Applicants selected for funding will be required to provide additional information listed below under "Award Notices." The application will then be forwarded to EPA's grants administration office for award in accordance with the EPA's procedures.

Applicants to be recommended for funding will be required to submit additional certifications and an electronic version of the revised project abstract. They may also be asked to provide responses to

comments or suggestions offered by the peer reviewers, a revised budget, and/or to resubmit their proposal. EPA Project Officers will contact Principal Investigators to obtain these materials. Before or after an award, applicants may be required to provide additional quality assurance documentation.

All researchers considered for a grant by the Environmental Protection Agency, must note the following information:

The primary EPA Strategic Goal, Objective and Sub-objective that relates to this solicitation is: Goal 4: Healthy Communities and Ecosystems, Objective 4.5: Enhance Science and Research, Sub-objective 4.5.2 Conduct Relevant Research. EPA's Strategic Plan can be found on the following web page: https://www.epa.gov/ocfo/plan/2003sp.pdf.

The official notification of an award will be made by the Agency's Grants Administration Division. Applicants are cautioned that only a grants officer is authorized to bind the Government to the expenditure of funds; preliminary selection by the NCER Director in the Office of Research and Development does not guarantee an award will be made.

EPA Award Notices:

Customarily, applicants are notified about evaluation decisions within six months of the application closing date. A summary statement of the scientific review by the peer panel will be provided to each applicant with an award or declination letter.

Applicants to be recommended for funding will be required to submit additional certifications and an electronic version of the revised project abstract. They may also be asked to provide responses to comments or suggestions offered by the peer reviewers, a revised budget, and/or to resubmit their proposal. EPA Project Officers will contact Principal Investigators to obtain these materials. Before or after an award, applicants may be required to provide additional quality assurance documentation.

Nonprofit applicants recommended for funding will be subject to a preaward administrative capability review consistent with sections 8.b, 8.c, and 9.d of EPA Order 5700.8, EPA Policy on Assessing Capabilities of Non-Profit Applicants for Managing Assistance Awards (https://www.epa.gov/ogd/grants/regulations.htm).

2. Administrative and National Policy Requirement

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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