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


Development of High-Throughput Screening Approaches for Prioritizing Chemicals for the Endocrine Disruptors Screening Program

Opening Date: October 25, 2002
Closing Date: January 29, 2003

Summary of Program Requirements
Specific Areas of Interest
Standard Instructions for Submitting an Application
Sorting Code

Get Standard STAR Forms and Instructions (http://www.epa.gov/ncer/rfa/forms/)
View NCER Research Capsules (http://www.epa.gov/ncer/publications/topical/)
View research awarded under previous solicitations (http://www.epa.gov/ncer/rfa/archive/grants/)

General Information

Program Title: Development of High-Throughput Screening Approaches for Prioritizing Chemicals for the Endocrine Disruptors Screening Program

Synopsis of Program:

The U.S. Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications for new approaches that can lead to the development of high-throughput screening systems to assist in prioritization of chemicals for further screening and testing of their potential as endocrine disruptors. In view of the estimated tens of thousands of chemicals under consideration for screening for endocrine disrupting activity, it is essential that rapid, sensitive, and reproducible high-throughput screening systems be developed. This request for applications invites research proposals that explore novel approaches to the development of such systems for identifying chemicals with estrogen, androgen, or thyroid hormone activities.

Contact Person(s):
David Reese; Phone: 202-564-6919; email: reese.david@epa.gov
Elaine Francis; Phone: 202-564-6789; email: francis.elaine@epa.gov

Applicable Catalog of Federal Domestic Assistance (CFDA) Number(s): 66.500

Eligibility Information:
See full announcement for eligibility information.

Award Information:
Anticipated Type of Award: Grant
Estimated Number of Awards: Approximately four to five
Anticipated Funding Amount: Approximately $1.5 to 2 million
Potential Funding per Grant: Up to $400,000 total during a period of up to 3 years

Sorting Code(s):
The sorting code for applications submitted in response to this solicitation is

Deadline/Target Dates:
Letter of Intent Due Date(s): None
Application Proposal Due Date(s): January 29, 2003


Concerns have persisted for several decades that normal endocrine system functions in humans and wildlife are being adversely affected by exposure to various chemical contaminants in the environment. These chemicals, commonly referred to as endocrine disrupting chemicals (EDCs), endocrine disruptors, or hormonally active agents, are thought to interfere with one or more aspects of the normal endocrine functions that are responsible for the maintenance of homeostasis and the regulation of developmental processes. Because of its broad scope and high level of concern, the EDC issue has been given high priority by both national and international agencies.

EPA's Office of Research and Development (ORD) identified research on endocrine disruptors as one of it high-priority topics in developing the ORD Strategic Plan (USEPA 1996, 1997, 2001). In 1998, ORD published a research plan that guides its intramural and extramural research program on EDCs (http://www.epa.gov/ORD/WebPubs/final/revendocrine.pdf), (USEPA, 1998). EPA coordinates its research with other federal agencies through an interagency working group. In 1995, the Committee on Environment and Natural Resources (CENR), under the President's National Science and Technology Council (NSTC), identified endocrine disruptors as an initiative and established an interagency working group, that was chaired by ORD/EPA and included representatives of 14 federal agencies. The CENR working group: (1) developed a framework for federal research related to the human health and ecological effects of EDCs, (2) developed a data base of federally funded research on EDCs, and (3) overlaid the framework with the inventory to identify high priority research gaps in the federal portfolio (Reiter et al., 1998). To begin to address some of the data gaps that were identified, several multi-agency solicitations for research proposals have been issued. The National Research Council (NRC), at the request of EPA, the Department of the Interior, and the Centers for Disease Control and Prevention, conducted a comprehensive, critical evaluation of the scientific literature, and identified research needs in its report "Hormonally Active Agents in the Environment" (NRC, 1999).

In the international arena, EDCs were identified as a high priority issue at the 1997 Environmental Leader's Summit of the Eight. Among the recommended action items, support was given to update and expand the US federal inventory to establish a global endocrine disruptors research inventory and to develop a global state-of-the-science review (WHO, 2002).


The authorities and responsibilities of the Environmental Protection Agency (EPA) are mandated primarily by thirteen major environmental statutes, the overall goal of which is to protect human health and the environment. Many of these statutes are concerned with protecting humans and wildlife from the adverse effects of exposure to synthetic chemicals released into the environment. Two of the most recent environmental laws, the Food Quality Protection Act (FQPA) of 1996 and the Safe Drinking Water Act Amendments (SDWA) of 1996 both contain provisions related to determining whether pesticides or chemical substances found in or on food or in drinking water sources may have estrogenic or other endocrine effects. FQPA specifically requires EPA to develop a screening and testing program for this purpose. To achieve this goal, the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) was established to advise the Agency on implementing the provisions of these two acts. This activity is currently being carried out by the EPA's Endocrine Disruptor Screening Program (EDSP). Based on existing science and EPA testing authorities, EDSTAC recommended that the screening program not be limit to the provisions of FQPA and SDWA but be extended to include screening for EDCs with androgen and thyroid hormone activities, ecological effects, and an expanded universe of chemicals and mixtures (http://www.epa.gov/scipoly/oscpendo/history/), (EDSTAC, 1998).

EPA's proposed statement of policy (http://www.epa.gov/scipoly/oscpendo/fr122898_1.pdf), (63 FR 71542-71568) reports that chemicals to be prioritized for endocrine disruptor screening and testing include pesticide chemicals, commercial chemicals, and environmental chemicals. The universe of chemicals is estimated to be about 87,000. EPA will use a tiered approach consisting of sorting, priority setting, Tier 1 screening and Tier 2 testing to determine whether a substance may have an adverse endocrine effect in humans or wildlife.

In the 2000 Report to Congress on the EDSP (http://www.epa.gov/scipoly/oscpendo/reporttocongress0800.pdf), EPA indicates that although EDSTAC recommended the use of high throughput pre-screening (HTPS) for priority setting, a feasibility study conducted by EPA demonstrated that, at the time, the HTPS technology and assay systems were not yet sufficiently developed for routine application. HTPS was initially viewed as a rapid, efficient means to provide preliminary endocrine effects data; since all processes are automated and can be programmed to run continuously, large numbers of samples can be screened in a relatively short period of time using this technology. EPA is still considering applying this technology when development has sufficiently progressed for application in a regulatory program.

The Report to Congress also affirms EPA's commitment to minimizing the number of animals that will be used in implementing EDSP, and to incorporating alternative test methods, where appropriate. It acknowledges that new and revised toxicological test methods are being developed that incorporate advances in molecular and cellular biology and that hold promise for reducing animal use in testing in the future.


In view of the estimated 87,000 chemicals under consideration for screening for endocrine disrupting activity, it is essential that rapid, high-throughput screening systems be developed to assist in prioritization of chemicals for further screening and testing. The Tier I battery of screens with high-throughput capabilities currently under evaluation by the EPA include estrogen and androgen receptor binding and reporter gene assays. As the science progresses in this area, improvements can be made on existing screening strategies and approaches. This RFA solicits research proposals that explore new approaches to the development of high-throughput screening systems for identifying chemicals with estrogen, androgen, or thyroid hormone activities.

New approaches should have the potential for making significant advances over existing EDC screens in speed, high-throughput capability, sensitivity, reproducibility, and reduction in animal usage in a screening and testing program. Approaches focusing on: classic ligand-steroid receptor-coregulator/cofactor interactions; non-genomic mechanisms of steroid hormone action; or mechanisms involving synthesis, metabolism, or degradation of estrogens, androgens, and thyroid hormones are of interest. Flexibility in basic design that would facilitate, for example, the identification of EDCs with both agonist and antagonist activities, allow screening to be carried out across vertebrate classes and endocrine-responsive tissues, and allow incorporation of new information as it becomes available is a desirable goal of any project. Two examples around which new high-throughput approaches may be developed include novel cell-based reporter assays, including prokaryotic and eukaryotic two-hybrid systems, and non-cellular systems such as the use of recombinant receptor and co-regulator functional protein domains as molecular sensors for detecting EDC activity. All approaches that have the potential for making significant advances in screening speed, high-throughput capability, sensitivity, reproducibility, and reduction in animal usage in a screening and testing program are of interest and will be considered.

This RFA supports basic research that will be necessary for the future development of more efficient approaches for detecting EDCs and should not be viewed as a contract to develop and validate new EDC screens. Adequate demonstration should be provided, however, that the proposed research projects have the potential for forming the basis of a new generation of high-throughput EDC screens.

In view of the inherent multi-disciplinary nature of this request, submission of proposals from groups of investigators that can bring a range of necessary expertise to the project is encouraged.


EDSTAC. August 1998. Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report.

Food Quality Protection Act. 1996. Public Law 104-170.

National Research Council. 1999. Hormonally Active Agents in the Environment. National Academy Press: Washington, DC.

Reiter, LW, C DeRosa, RJ Kavlock, G Lucier, MJ Mac, J Melillo, RL Melnick, T Sinks, BT Walton. 1998. The U.S. Federal Framework for Research on Endocrine Disruptors and an Analysis of Research Programs Supported during Fiscal Year 1996. Environmental Health Perspectives 106(3): 105-113.

Safe Drinking Water Act Amendments. 1996. Public Law 104-182.

USEPA. 1996. Strategic Plan for the Office of Research and Development. Washington, DC, EPA/600R-96-059.

USEPA. 1997. 1997 Update to ORD's Strategic Plan. Washington, DC, EPA/600/R-97/015.

USEPA. 1998. Research Plan for Endocrine Disruptors. Office of Research and Development. Washington, DC. EPA/600/R-98/087.

USEPA. 2001. Office of Research and Development Strategic Plan. Washington, DC, EPA/600/R-01/003.

World Health Organization (WHO). 2002. International Programme on Chemical Safety. Global Assessment of the State-Of-the-Science of Endocrine Disruptors. Eds. T Damstra, S Barlow, A Bergman, R Kavlock. GVD Kraak.


It is anticipated that a total of approximately $1.5 to 2 million will be awarded, depending on the availability of funds. EPA anticipates funding approximately four to five grants under this RFA. The projected award per grant is $125,000 to $133,000 per year total costs, for up to 3 years. Requests for amounts in excess of a total of $400,000, including direct and indirect costs, will not be considered.


Academic and not-for-profit institutions located in the U.S., and state or local governments, are eligible under all existing authorizations. Profit-making firms are not eligible to receive grants from EPA under this program. Federal agencies and national laboratories funded by federal agencies (Federally-funded Research and Development Centers, FFRDCs) may not apply.

Federal employees are not eligible to serve in a principal leadership role on a grant. 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 principal investigator, but may not direct projects on behalf of the applicant organization or principal investigator. The principal investigator's institution may provide funds through its grant from EPA to a 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 employees may not receive salaries or in other ways augment their agency's appropriations through grants made by this program. However, federal employees may interact with grantees so long as their involvement is not essential to achieving the basic goals of the grant.1 The principal investigator's institution may also 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, etc. A written justification for federal involvement must be included in the application, along with an assurance from the federal agency involved which commits it to supply the specified service.

1EPA encourages interaction between its own laboratory scientists and grant principal investigators for the sole purpose of exchanging information in research areas of common interest that may add value to their respective research activities. However, this interaction must be incidental to achieving the goals of the research under a grant. Interaction that is "incidental" is not reflected in a research proposal and involves no resource commitments.

Potential applicants who are uncertain of their eligibility should contact Jack Puzak in NCER, phone (202) 564-6825, Email: puzak.jack@epa.gov.


A set of special instructions on how applicants should apply for an NCER grant is found on the NCER web site, http://www.epa.gov/ncer/rfa/forms/, Standard Instructions for Submitting a STAR Application. The necessary forms for submitting an application will be found on this web site.


The need for a sorting code to be used in the application and for mailing is described in the Standard Instructions for Submitting a STAR Application. The sorting code for applications submitted in response to this solicitation is 2003-STAR-B1.

The deadline for receipt of the applications by NCER is no later than 4:00 p.m. ET, January 29, 2003.


Further information, if needed, may be obtained from the EPA official indicated below. Email inquiries are preferred.

David Reese (202) 564-6919

Elaine Francis (202) 564-6789


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