Application of biomarkers to environmental health and risk assessment.

The U.S. Environmental Protection Agency (EPA) Office of Research and Development, National Center for Environmental Research (NCER), through its Science to Achieve Results (STAR) program, is issuing this request for applications (RFA) for research that provides validation, interpretation, and/or application of currently known biomarkers to environmental health and risk assessment. Of special interest is the utilization of multiple biomarkers that can fill knowledge gaps across different points of the exposure--dose--effect continuum and/or that can be applied in a clinical setting. The proposals should focus on one or more of the following investigational areas:

1) Animal or epidemlology studies that explore the relationship between biomarkers of exposure and measures of subclinical disease (early biological effect or altered structure/function). Additionally, these studies could be expanded to explore the relationship between the subclinical disease measure and the actual clinical disease.

2) Mechanistic studies (e.g., using genomics or proreomics) of toxicant response linked to clinical disease--for example, the identification of the functional relevance of proteins where genetic polymorphisms have been found to modify the effect of an environmental exposure on a disease end point.

3) Studies to validate the utility of biomarkers for use in large population studies (e.g., reliability, predictive value, sensitivity, specificity, affordability, applicability to the general population and susceptible subpopulations).

Risk assessment is an essential tool for setting environmental and occupational standards that limit exposure to environmental agents with the aim of protecting human health. However, risk assessment is a relatively new discipline, and currently available methods and detailed information on exposure and toxicity are frequently inadequate to fully satisfy, the demands for accurate risk characterization. More information is needed regarding the events leading from exposure to dose to effect. Biological markers have significant potential for strengthening current risk assessments, for example, by filling in important gaps in the exposure--disease continuum.

Although the field of biomarkers is still relatively new, many different analytical techniques have been developed to quantify such events as exposure to a certain chemical or early biological events resulting from exposures. Problems exist with many current biomarkers in that they, have not been validated for use in large population studies, and their significance for predicting the risk of clinical disease is unknown. In other words, although a marker may indicate exposure to a certain environmental chemical, it may not be well understood how that marker relates to other events in the toxicological paradigm. For example, does the marker of exposure relate to an exposure dose, an internal dose, a target organ dose, or a biologically effective dose? To what types of effects--such as early biological effects and disease end points--can this biomarker be linked? Additionally, what does this mean in terms of quantifying risk of an adverse effect or in identifying susceptible groups, or even in terms of identifying early disease stages?

Successful proposals must 1) address biomarkers that are measured in biological media; an actual disease end point is not considered to be a biomarker of effect; 2) focus on one of the following emphasis areas: the reproductive system, the brain/nervous system, the immune system, or the respiratory system; 3) link the biomarker(s) to a toxic end point through an observation of a statistical relationship between the marker and the end point or through a link to a mechanism of action (key precursor event); 4) be relevant or related to environmental exposures; and 5) consider, as much as possible, issues of validation, robustness, and capacity for high-throughput applications.

Institutions of higher education and not-for-profit institutions located in the United States, as well as tribal, state, and local governments, are eligible to apply. See the complete announcement for more details.

It is anticipated that a total of approximately $3 million will be awarded, depending on the availability of funds. Approximately 4-6 awards will be made under this RFA. The projected award per grant is $150,000-250,000 per year total costs, for up to 3 years. Requests for amounts in excess of a total of $750,000, including direct and indirect costs, will not be considered.

A set of special instructions on how applicants should apply for an NCER grant along with the forms required for application are found on the NCER website at http://es.epa.gov/ncer/rfa/forms/, Standard Instructions for Submitting a STAR Application. The deadline for receipt of applications is 11 February 2004. Complete information on this RFA is located at http://es.epa.gov/ncer/rfa/2004/2004_biomarkers.htmh

Contact: Kacee Deener, 202-564-8289, e-mail: [e-mail] (e-mail inquiries are preferred). Reference: 2004-STAR-D1