RFA 96-2

The Health Effects Institute
"A Partnership of the U.S. Environmental Protection Agency and Industry"

Request for Preliminary Application 96-2
(From September 1996 Health Effects Institute RFA book)

Request for Preliminary Applications on the Health Effects of Exposure to Air Pollutants from Motor Vehicle Emissions

Introduction Application Process and Deadlines Evaluation Process

INTRODUCTION

This RFPA provides a mechanism for investigators whose area of interest falls outside of the current RFA, but is compatible with the HEI research program and mission, to apply for HEI funds. HEI is interested in receiving applications for research on novel and important aspects of the health effects of air pollutants derived from motor vehicle emissions outside the specific area delineated in RFA 96-1.

Preliminary applications will be reviewed periodically by the HEI Research Committee, which then will invite submission of full applications for the most promising suggestions. Full applications will be evaluated by several peer reviewers before consideration by the Research Committee.

Up to $250,000 per year is available for studies funded this year through the preliminary application process. We encourage applications for small studies and pilot studies and suggest limiting the budgets to $70,000 in direct costs per year.

THE HEI RESEARCH PROGRAM AND RESEARCH PRIORITIES

Since 1983, HEI's research program has addressed a broad range of questions about the health effects of air pollutants derived from motor vehicles emissions, including aldehydes, carbon monoxide, diesel particles and associated compounds, methanol, nitrogen oxides, and ozone. Several studies have addressed the effects of exposure to more than one pollutant. HEI's strategic plan, developed in 1994, designates three high priority research areas: air toxics, particles, and oxygenated fuels and additives (such as MTBE). Since then HEI has initiated research programs in all of those areas as well as some research on oxidants.

HEI's current air toxics research focuses mainly on studies to improve the extrapolation of health effects of benzene and 1,3- butadiene from high to low doses and across species. A major part of that program has been development of biomarkers, which will soon be validated in transitional epidemiology studies funded by HEI. The Research Committee sees a need for development of similar studies for aldehydes and possibly other air toxics. The HEI particles research program includes the Particle Epidemiology Evaluation Project, which, in the first phase, focused on replicating key analyses of the relation between particulate air pollution and acute mortality and morbidity and investigating the possible confounding effects of weather and other pollutants. In Phase II, the work will be extended to analyze the health effects of several pollutants, including particulate matter, for their relation to respiratory and cardiovascular morbidity and mortality using a U.S.-wide data set. In addition, eight ongoing epidemiologic and toxicologic studies are aimed at determining whether the acute effects of particles observed in humans can be replicated in compromised animal models, identifying populations sensitive to effects of particle exposure, and investigating mechanisms by which short-term increases in particle levels might produce mortality and morbidity. From a 1995 RFA on comparative metabolism and health effects of ethers added to gasoline, several studies will compare metabolism of MTBE, ETBE, and TAME in rats and humans, investigate the role of different P450 isozymes in the metabolism of these ethers, and determine the effects of co-exposure to gasoline vapors on the uptake and metabolism of MTBE in rats.

The ultimate goal of research funded by HEI is to provide data that can be used in regulatory decisions and in decisions on the use of future technologies and fuels and will provide better information for risk assessment. Sometimes the connection between HEI studies and these decisions is direct, but at other times new methods must be developed or biological mechanisms must be understood before studies of human health effects can be launched. Thus, HEI's research program is comprised of a variety of studies, which in either the near or the long term are important for obtaining better information on the human risks of exposure to pollutants from motor vehicles.

HEI studies have covered a wide range of designs: modeling, experiments with cell cultures, animal studies, controlled human exposure studies, and epidemiologic investigations. There are several cross-cutting issues that the Research Committee would like to emphasize in HEI-funded studies. One of these is to identify and evaluate effects in susceptible groups that may respond at lower levels of exposure than "normal subjects". Another important focus is to improve methods for understanding mechanisms by which toxic agents cause injury and disease and to quantify the actual dose of a pollutant received by tissues, cells, and macromolecules. In all studies, accurate characterization of exposure is important. Studies that address the effects of multiple pollutants are important in understanding health effects of ambient exposure. Finally, because the ultimate goal of HEI's research is an understanding of effects in people, human studies and studies to improve extrapolation from animals to humans are an important part of HEI's program.

SUMMARY

While we feel that an understanding of HEI's research priorities is important for applicants to the preliminary application process, and would like in most cases to fund studies that are responsive to those, an important goal of this preliminary application process is to provide a means for investigators to suggest new areas of research. Thus, applications will be considered not only on issues raised in the discussion above and in HEI's strategic plan, but also on other issues related to improving our understanding and assessment of the health risks of exposure to motor vehicle emissions and secondary pollutants derived from them and the whole air pollution mixture to which they contribute. Emissions from vehicles using conventional, reformulated, oxygenated, and diesel fuels are of interest.

In general, applications should include studies at concentrations that occur in the environment. Initial experiments using either new techniques or investigating mechanisms of health effects may need to start at pollutant concentrations higher than ambient levels, but will only be considered if there is a real likelihood that the effects studied will be relevant to understanding effects at environmentally relevant concentrations. Although HEI is interested in both in vivo and in vitro methods, for the latter studies it is important to explain the relationship of the assay system to the in vivo situation being modeled. Methods using isolated tissues, cells, or subcellular fractions should be appropriate for the physical characteristics of the inhaled chemicals and the metabolic transformations that may occur in vivo before target tissues are exposed. The respiratory and central nervous systems are clearly important target sites, although other organ systems may also be appropriate for study if a strong rationale links them to possible toxic effects of automotive pollutants.

APPLICATION PROCESS AND DEADLINES

The general preliminary application process consists of two stages. The first stage involves the submission of a preliminary application, which is reviewed by the Research Committee. If the Research Committee expresses interest in the study, then the investigator is asked to prepare a full application.

PRELIMINARY APPLICATION

The preliminary application should contain two elements: a description of the project plan containing an outline of the intended experimental techniques and a rationale for the proposed study indicating its importance in light of current insights and knowledge about vehicle emissions. It is essential that both the scientific questions being addressed and the methodological approach be explained clearly. When critical, the experience of the investigators and the availability of any special equipment and facilities should be mentioned. The preliminary application must be no more than five pages in length.

In addition to the application, a brief curriculum vitae of the principal investigator and co-investigators should be provided. Detailed budgetary information is not desired in the preliminary application, but investigators should indicate the estimated scope of the project in terms of time and money.
Five copies of the preliminary application are needed for our review process.

Deadlines for Preliminary Applications: Preliminary applications may be submitted at any time and will be discussed at the first Research Committee meeting following their receipt at HEI. Investigators planning to submit a preliminary application can call HEI for submission deadlines for consideration of their applications at the next meeting.

Preliminary applications and questions regarding them should be directed to:

Health Effects Institute
955 Massachusetts Avenue
Cambridge, MA 02139
Tel: (617) 876-6700
or
email facts@healtheffects.org

FULL APPLICATION
Investigators asked to prepare a full application will be sent the appropriate application forms to be completed. The deadline for the full application will be agreed upon between the investigator and the HEI staff. Five copies of each full application are needed by HEI for the review process.

EVALUATION PROCESS

PRELIMINARY APPLICATION

The HEI Research Committee will evaluate preliminary applications received in response to RFPA 96-2 at its regularly scheduled meetings. The preliminary applications will be reviewed in terms of relevance of the proposed research to the scientific problem being investigated and to the current objectives of HEI's research program. Investigators will be informed within one to four months of the submission date whether to submit a full application.

FULL APPLICATIONS

Full applications will be evaluated in a two-stage process. First, scientists selected for their relevant expertise will evaluate the applications according to the following criteria:

Scientific merit of the research design, approaches, methodology, analytical methods, and statistical procedures;

Personnel and facilities, including

* Experience and competence of the principal investigator and scientific staff
* Adequacy of effort on the project by scientific and technical staff
* Adequacy of facilities; and

Reasonableness of the proposed cost.

The Research Committee will then review full applications with consideration of the reviewers' comments and of the ways the proposed research could improve the understanding of the specific problem under investigation. The Research Committee makes final recommendations regarding funding of studies to the Institute's Board of Directors, which makes the final decision.

Request for Preliminary Application 96-2 (From September 1996 Health Effects Institute RFA book)

Request for Preliminary Applications on the Health Effects of Exposure to Air Pollutants from Motor Vehicle Emissions

APPLICATION PROCESS AND DEADLINES

EVALUATION PROCESS

Request for Preliminary Application 96-2
(From September 1996 Health Effects Institute RFA book)