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

APPENDIX A:
Strategic Plan Update — October 1998

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HEI Strategic Plan for the Health Effects of Air Pollution (1998–2000)

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INTRODUCTION

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The Health Effects Institute is an independent, nonprofit corporation chartered in 1980 to provide high-quality, impartial, and relevant scientific information on the health effects of pollutants from motor vehicles and other sources in the environment. Supported jointly by the U.S. Environmental Protection Agency (EPA) and industry, HEI has funded 180 studies, published about 100 Research Reports, and contributed important research findings on the health effects of a variety of air pollutants, including carbon monoxide, methanol, diesel exhaust particles, nitrogen oxides, and ozone. The current research programs focus on air toxics, ambient particles, and oxygenates added to gasoline.

To accomplish its mission, HEI:

• Identifies the highest priority areas for health effects research that targets pollutants and issues of greatest concern, avoids unnecessary duplication of other research, and responds to the changing public and technological environment;
• Funds and oversees the conduct of high-quality research in the priority areas, fostering when appropriate integrated and multi-institute efforts;
• Provides intensive, independent review of HEI-supported and related research that enhances the understanding and credibility of the results;
• Integrates HEI's research results with those of related studies into coherent, broader evaluations of the health effects of a fuel or technology; and
• Communicates the results of HEI research and analyses to public and private decision makers in an understandable and timely way.

HEI's success is dependent on cooperation and communication among its many constituent groups: the sponsors, other public interests, Research and Review Committees, investigators, and staff. HEI's Board of Directors and President consult with these constituents, set the goals of the Institute, and oversee its work. They consider and respond to the diverse views of sponsors on priorities and also take into consideration the views of others in the public and private sectors who have an interest in understanding environmental and health issues, who are important audiences for the results of HEI's work, and without whose acceptance the effectiveness and impact of the Institute would be reduced. The Research Committee works with the Institute's scientific staff to develop and oversee HEI's research program, and the Review Committee, which has no role in selecting or overseeing the studies, works with other scientific staff members to evaluate and interpret the final report from each study. Sometimes ad hoc expert panels are formed to oversee special projects.

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BUILDING A STRATEGIC VISION

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The HEI Strategic Plan for Vehicle Emissions and Fuels (1994—1998) was developed with ideas and input from a wide range of HEI's sponsors and other constituents, and finalized after a broad-based workshop at the 1994 HEI Annual Conference. Since the plan was issued in August 1994, the process of consulting with sponsors has continued. At the 1995, 1996, and 1997 Annual Conferences, HEI has presented and discussed with conference participants updates of the strategic plan, including accomplishments of the previous year and plans for the coming year, to inform its developing plans. Early drafts of Requests for Applications (RFAs) for research have been circulated to sponsors for input before finalizing them.

The HEI Strategic Plan for Vehicle Emissions and Fuels (1994—1998) described the projected HEI research program and scientific review activities for a five-year period. This Strategic Plan Update reviews HEI's progress and describes future scientific activity. It attempts to anticipate the major questions about the health effects of pollutants and new technologies that are likely to face policymakers and manufacturers. The strategies presented in the plan serve as a guide for HEI in developing detailed annual research and review plans.

HEI's strategic plan reviewed a number of potential areas for research, including the combined effects of pollutants present in the air pollution mixture, the health effects of ozone, and the health effects of new technologies and fuels. Three areas were selected as having the highest current priority:

• Air toxics
• Ambient particles
• Oxygenated fuels and additives to gasoline

Since 1994, HEI has selected 60 new studies for funding on these priority topics and also has conducted special reviews on the health effects of diesel exhaust particles and of oxygenates added to gasoline. In addition to specific pollutants of interest, HEI's strategic plan discusses several cross-cutting issues that should be emphasized in all HEI research efforts to which they are relevant. These include identifying sensitive populations, improving extrapolation from high to low exposure levels and among species, and understanding the mechanisms of toxicity.

HEI has long recognized that most air pollutants from motor vehicles are not contributed uniquely by mobile sources but are also emitted by other sources. Thus HEI's research on such pollutants as ambient particles, ozone, and air toxics cannot be considered narrowly as research on motor vehicle emissions. HEI's research program also has recognized that understanding the effects of exposure to each of several individual pollutants does not provide a complete picture of the health effects of these pollutants together in ambient air. HEI has funded some research looking at exposure to more than one pollutant, such as ozone plus acid aerosols, and Mexico City air. The 1996 Strategic Plan Update reflected the broader significance of HEI's research and review activities by designating it the HEI Strategic Plan for the Health Effects of Air Pollution. While emphasizing the broader relevance of its research program, HEI intends to maintain its efforts to study in a timely way pollutants that are specific to motor vehicles, such as particles in exhaust from diesel engines and metal emissions from motor vehicle, and is striving to project further into the future the possible new fuels and technologies for which health effects information will be needed to inform decisions about their future widespread use.

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MEETING THE CHALLENGES

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An independent research organization faces several critical challenges in designing and implementing a strategic plan. HEI's plan identifies and addresses three key challenges.

Forecasting the Future

As new technologies and fuels for vehicles are considered, HEI would like to generate health effects data that can be used to compare the public health risks from using conventional fuels and technologies with the risks associated with new fuels and technologies. Although a new fuel or technology may reduce some pollutants, it may also increase other pollutants (e.g., adding MTBE to gasoline may decrease carbon monoxide but increase aldehydes), or it may reduce particle mass but alter the size or chemical composition of the particles. In implementing its strategic plan, HEI is trying to work closely with its sponsors to identify and assess emerging technologies and fuels at the earliest possible time.

Informing the Risk Assessment and Regulatory Processes

Although HEI does not perform formal risk assessments of individual pollutants, technologies, or fuels, it must tailor its research and evaluation efforts to inform the broader risk assessment process undertaken by government and industry. HEI has enhanced its efforts to focus on research and review activities that address critical gaps in risk assessment for particular pollutants. For example, HEI's current research program on the air toxics benzene and 1,3-butadiene is seeking new ways to extrapolate health risks determined at higher doses to low doses and from animals to humans. In addition, HEI has provided reports from the NTP/HEI Collaborative Ozone Project and the first phase of the Particle Epidemiology Evaluation Project in time for the results to be incorporated into EPA's criteria documents for ozone and particulate matter, respectively. HEI is making plans for the timing of reports of ongoing and new PM studies to optimize the information that will be contributed in time to be incorporated into the next PM criteria document.

Broadening the Base of Support

Much of HEI's annual budget, over three-fourths of which goes directly to research and related scientific activities, is currently jointly funded by the EPA and manufacturers and marketers of motor vehicles and engines in the United States. In addition to these core sponsors, HEI is also receiving support for some air toxics work from the Chemical Manufacturers Association and from its European counterpart, Conseil Europeen de l'Industrie Chemiqué (CEFIC); for diesel research, from the California Air Resources Board and the Engine Manufacturers Association; and for work on ambient particulate matter, from the European Commission and the American Petroleum Institute. In the past, HEI has received support for special projects from other sources, and has also co-funded studies with the National Institute of Environmental Health Sciences and the Department of Energy. These sources of additional support allow HEI to fund more research than its core budget would allow.

With enhanced financial support from Congress, the U.S. EPA, and industry, HEI is expanding its funding base to support increased research on ambient particles, an area where intensive research is needed to resolve questions about the health effects of particulate matter from motor vehicles, fuels, and other sources, including the characteristics of particles that affect toxicity. This initiative also includes enhancing support from European governments and industries that are addressing many of the same questions. An increased sponsor and funding base will allow HEI to spend a higher proportion of its funds directly on research and related scientific activities.

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ACCOMPLISHMENTS IN 1994–1998

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This section summarizes the activities that HEI has undertaken since establishing its strategic plan in August 1994.

Research and Review Activities in Priority Areas

HEI has implemented research programs and carried out special review activities in the three high-priority areas designated in the 1994 strategic plan and has continued and completed research on several ozone issues.

Ambient Particles

• Particle Epidemiology Evaluation Project and NMMAPS: In the fall of 1994, HEI funded an independent evaluation of several existing time-series epidemiologic studies showing an association between increases in ambient particulate levels and morbidity and mortality. The major goal of this project was to determine whether the findings of these studies could be replicated by other investigators. Two reports were issued from Phase I of this project: Particulate Air Pollution and Daily Mortality; Replication and Validation of Selected Studies (August 1995) and Particulate Air Pollution and Daily Mortality; Analyses of the Effects of Weather and Multiple Air Pollutants (March 1997). Phase II of the project, called the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), which began in December 1996, is extending the Phase I work by using a U.S.-wide data set to analyze the health effects of several pollutants, including particulate matter, whose relative levels vary in different regions, for their relation to respiratory and cardiovascular morbidity and mortality. The study is also investigating the extent to which increases in daily mortality represent only a small reduction in life expectancy, and how to estimate and correct for errors in exposure measurement.
• Epidemiology Reanalysis Project: In the spring of 1997, HEI decided to undertake a reanalysis of the results of two studies, the Harvard Six-Cities Study and the American Cancer Society Study, whose findings of health effects associated with long-term exposure to fine particulate air pollution contributed to the scientific support for the 1997 PM National Ambient Air Quality Standards. HEI held a workshop in June 1997 at which the Expert Panel overseeing this project obtained broad and useful suggestions on its scope from participants with different perspectives. An analytic team was selected in the fall of 1997 from proposals received in response to A Request for Qualifications for Epidemiolgists and Statisticians to Participate in a Reanalysis of Cohort Studies of Long-Term Mortality and Particulate Air Pollution. The Principal Investigator (Dr. Daniel Krewski) presented a draft analytic plan for discussion at the HEI Annual Conference in April 1998; a modified plan responsive to comments at the conference was approved by the Expert Panel for the Epidemiology Reanalysis Project in June 1998. The data have now been obtained by Dr. Krewski and his team, and they expect to complete both replication and sensitivity analyses by December 1999.
• Studies of Populations at Risk and Mechanisms of Action: From RFA 94-2, Particulate Air Pollution and Daily Mortality: Identification of Populations at Risk and Underlying Mechanisms, as well as from the preliminary application process, HEI funded eight epidemiologic and toxicologic studies aimed at determining whether the acute effects of particles observed in time-series epidemiologic studies can be replicated in compromised animals models, identifying populations sensitive to the effects of particle exposure, investigating mechanisms by which a short-term increase in particle levels might cause mortality and morbidity, and understanding which particle characteristics are associated with health effects. Five additional mechanistic studies, funded from RFA 96-1, Mechanisms of Particle Toxicity: Fate and Bioreactivity of Particle-Associated Compounds, were funded to address hypotheses about which constituents of particles may be toxicologically important.
• Expanded PM Research Program: In the past year, HEI worked with EPA, motor vehicle sponsors, and the scientific community to develop an RFA for an expanded research program on particulate matter that would address some critical exposure and health effects issues. This included organizing a workshop in November 1997 for in-depth discussion of a draft RFA, and then developing a more focused RFA based on the recommendations and discussion at that workshop and at an EPA workshop held later that month. HEI issued RFA 98-1, Characterization of Exposure to and Assessment of Health Effects of Particulate Matter, in January 1998 to develop a targeted research program of coordinated studies of exposure and health effects that will provide results for the next review of the NAAQS for particulate matter. Eighteen studies have been approved for funding from this RFA; several of these have started.

Diesel Exhaust

An important subset of the work on ambient particles focuses on diesel exhaust. Some of the programs described under the heading Ambient Particles include studies to compare the toxicity of diesel particles with other types of particles, and the epidemiologic studies of ambient exposures of course include diesel particles. In addition, we have undertaken the following:

• Reports from HEI-Funded Studies: HEI published key Research Reports in 1994 and 1995 on studies in rats comparing the carcinogenicity of diesel exhaust and carbon black, a surrogate for diesel particles with little adsorbed organic material, and investigating the effects on DNA adducts and oncogenes. In 1996, HEI published a Research Report on a study that examined the physical and chemical characteristics of emissions from a 1988-model heavy-duty diesel engine with and without a ceramic particle trap and a 1991 engine with and without an oxidation catalytic converter. This study provided important information on the potential impact of new technologies on the size distribution of particles.
• Particle Characterization Workshop: In response to concern that efforts to decrease particle emissions from diesel engines might change the distribution toward smaller particles that might be more toxic, HEI held a Particle Characterization Workshop in December 1996. This workshop brought together physical scientists who make measurements on emissions and toxicologists who investigate health effects of particles. The goal was for these groups to share current knowledge about characteristics of particles in mobile source emissions and about the physical and chemical attributes that may be relevant to toxicity so that scientists and engineers measuring particles in emissions would be aware of additional parameters that may be useful in assessing the potential health impacts of changes in fuel formulation, engine design, or emissions control systems. A summary of the workshop was published in September 1997.
• HEI Special Report, Diesel Emissions, A Critical Analysis of Emissions, Exposure, and Health Effects: This report, released in April 1995 and presented to EPA's Clean Air Scientific Advisory Committee, capped 10 years of HEI-funded research to improve the science underlying assessments of the carcinogenicity of diesel exhaust. The report integrated toxicology, epidemiology, and exposure data and discussed the implications for assessing the cancer risk from diesel exhaust. It concluded that significant questions remain about using either the available animal data or human epidemiologic data to develop quantitative estimates of the potential cancer risks associated with the levels of diesel emissions.
• Workshop on Using Epidemiologic Data for Quantitative Risk Assessments of Diesel Exhaust: After issuing its Special Report on diesel exhaust, HEI worked with the California EPA, the World Health Organization, the U.S. EPA, and the National Institute of Occupational Safety and Health to organize a workshop on Diesel Exhaust: Considerations in the Use of Epidemiologic Data for Quantitative Risk Assessments. The purpose of this workshop, which was held in January 1996, was to discuss the use of epidemiologic data in developing quantitative risk assessments for the carcinogenicity of diesel exhaust. Topics for discussion included the strengths and weaknesses of the available epidemiologic and exposure data, sources and impacts of uncertainty and variability, and different modeling approaches.
• Diesel Epidemiology Expert Panel: In 1998 HEI organized a Diesel Epidemiology Expert Panel to follow up the issues discussed at the 1996 workshop Diesel Exhaust: Considerations in the Use of Epidemiologic Data for Quantitative Risk Assessments. The panel's charge is to review the epidemiologic data forming the basis of the current risk assessments of diesel emissions and to identify information gaps in order to make recommendations for the design of new studies to improve those assessments.
• Diesel Epidemiology Research: In May 1998, HEI issued RFA 98-3, Epidemiologic Investigation of Human Populations Exposed to Diesel Engine Emissions: Feasibility Studies, which solicited applications for short-term feasibility studies designed to provide information that will support the development of applications for full epidemiologic studies of the health effects of diesel exhaust. The RFA had two objectives: (1) to identify study populations that could provide reasonably precise estimates of small to moderate excesses of lung cancer of chronic cardiorespiratory disease; and (2) develop an exposure assessment strategy, including validation of measurement techniques, and development of approaches for using data generated by these techniques to make quantitative estimates of retrospective exposure to diesel engines. Applications to this RFA were submitted in July 1998, reviewed by an expert panel in early September, and then discussed by the Research Committee in mid-September. The Research Committee identified six studies of interest for funding.

Air Toxics

• Benzene and 1,3-Butadiene Studies: From a 1993 RFA, Novel Approaches to Extrapolation of Health Effects for Mobile Source Toxic Air Pollutants, HEI funded eight benzene and 1,3-butadiene studies aimed at improving extrapolation from high doses to low doses and across species. Some of these studies are developing biomarkers (for example, metabolites, adducts, genetic changes) that could be used in epidemiologic studies. Seven of these studies have ended and are under review by the HEI Review Committee.
• Transitional Epidemiology Studies: From applications submitted in response to RFQ 95-3, Transitional Epidemiology Studies for Benzene and 1,3-Butadiene Biomarkers, HEI funded two studies to validate benzene and 1,3-butadiene biomarkers, including those developed by HEI investigators (funded under RFA 98-3), in occupationally exposed populations. The goals of these studies are: (1) to obtain comparative information on biomarkers in relation to exposure levels in people and different animal species that could help scientists and regulators understand the relevance of results in animal studies to effects in people; and (2) to determine whether biomarkers measured in animal studies can be measured in blood and urine samples from people exposed occupationally to benzene or 1,3- butadiene and, if so, to determine the relation between biomarker levels and exposure levels. This information will be used to determine which biomarkers may be useful as markers of exposure or biological effects in epidemiologic studies looking at disease risk. Subjects in these studies are workers exposed to benzene in glue and shoe factories in China and workers exposed to butadiene in a monomer production facility and a styrene-rubber facility in the Czech Republic.
• Workshop on 1,3-Butadiene: HEI organized a workshop in collaboration with the European Commission, which took place in June 1998 in Brussels, Belgium. The workshop addressed important issues with respect to understanding human risk from exposure to of 1,3-butadiene. These include questions about the relevance of results in different animal species to effects in humans and the relevance of findings in butadiene workers to people exposed in ambient settings.
• Aldehydes RFA: The Research Committee identified several aldehydes of potential concern derived from motor vehicle emissions and other sources. These are formaldehyde, acetaldehyde, acrolein, crotonaldehyde, glyoxal, and methylglyoxal. HEI issued RFA 97-2, Assessing Personal Exposure to Selected Aldehydes Using Chemical and Biological Techniques, in September 1997 for studies to improve characterization of human exposure to aldehydes of interest. This information, which is important for assessing the potential health effects of these aldehydes, is sparse for most of these aldehydes. From this RFA, HEI selected three studies of interest for funding. The three studies take different approaches to evaluating exposure to aldehydes; they plan to study: (1) a sample of the general population; (2) residents of urban areas with high levels of pollution; (3) workers in diesel repair facilities, garages, and gasoline stations.
• Workshop on Metals: Metals are used in a variety of ways in motor vehicles; they are used in catalytic converters, as fuel additives to reduce certain emissions or improve engine performance, and are also found in brake pads. Metals comprise a complex groups of elements with a broad range of toxic effects; some are toxic at very low levels. To help define priorities for a research program on metals, HEI brought together experts from industry, government, and academia in February 1998 to inform the Research Committee about which additives were most likely to be used, how much is known about their chemical form and concentration in emissions, the toxicity of these emissions, and what research is being conducted. RFPA 98-4, Research on Metals Emitted by Motor Vehicles, in the October 1998 RFA Book, was based on this workshop.

Oxygenated Fuels and Additives to Gasoline

• Oxygenates Review: At the request of the U.S. EPA and the Centers for Disease Control and Prevention, and in conjunction with a broader review being conducted by the White House Office of Science and Technology Policy, HEI critically evaluated the health effects literature on MTBE and ethanol, the two most commonly used oxygenate additives, and issued the report Potential Health Effects of Oxygenates Added to Gasoline in April 1996. In addition to evaluating the potential health effects of the oxygenates themselves, the HEI Oxygenates Evaluation Committee also came to some overall conclusions about oxygenated gasoline.
• Ethers Research Program: HEI issued RFA 95-2, Comparative Metabolism and Health Effects of Ethers Added to Gasoline to Increase Oxygen Content, in August 1995. Three studies were selected for funding that are comparing metabolism of MTBE, ETBE, and TAME in rats and humans, investigating the role of different P-450 enzymes in the metabolism of these ethers, and determining the effects of coexposure to gasoline vapors on the uptake and metabolism of MTBE in rats. These studies started in the fall of 1996 and will continue through 1998.
• Methanol Research: Research Reports from three studies of the pharmacokinetics of methanol in different species and the developmental effects in rats exposed in utero were reviewed and published in 1996 and 1997. Two reports from a major study of developmental effects in monkeys exposed to methanol have been submitted for review, one on the adults and one on the offspring.

Ozone and Other Oxidants

• Reports Issued: HEI has reviewed and published many reports from its diverse ozone research programs in the past few years, including

(1) the NTP/HEI Collaborative Ozone Project, in which many investigators evaluated a comprehensive set of biochemical, physiological, and morphological endpoints in the respiratory system of rats after long-term exposure to ozone in conjunction with the National Toxicology Program's ozone carcinogenesis bioassay (13 reports);

(2) studies to develop ozone personal samplers to be used in epidemiologic studies;

(3) studies of the effects of combined or sequential exposure to ozone and acid aerosols in controlled human exposures;

(4) controlled human exposure studies investigating how individual differences in pulmonary function responses to exposure to ozone correlated with inflammatory responses;

(5) a study to improve the function of an instrument that measures ozone uptake in humans performing at different exercise levels; and

(6) Several reports from RFA 91-1, Epidemiologic Studies of the Health Effects of Long-Term Ozone Exposure. These include a study of health effects in children and efforts to develop methods for retrospectively estimating an individual's lifetime exposure to ozone.

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LOOKING AHEAD: RESEARCH AND REVIEW ACTIVITIES FOR 1998–2000

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At this time, HEI has active research programs on several air toxics, ambient particles, and ethers that are added to gasoline.

The effects of particulate air pollution have emerged as a significant public health issue. As described earlier, HEI has under way research to address important issues about the health effects of particles. In the past year HEI has expanded the scope of its program on particulate air pollution with eighteen new studies addressing critical health effects and exposure issues that were raised in the discussion surrounding the development of a revised National Ambient Air Quality Standard for particulate matter.

In addition to expanding its PM research program, in the past year HEI has:

• expanded its air toxics program by

adding research on exposure to aldehydes

issuing a request for research on metals emitted from motor vehicles in order to address concerns about exposure to metals that may be used as fuel additives to improve engine performance of decrease emissions

• identified six diesel feasibility studies for funding that will enable investigators to develop information for designing full diesel epidemiologic studies, and provide better applications to the RFA that HEI plans to issue in 1999

HEI's current strategic plan was issued in 1994, and has been updated several time since then. It is now time to again consider broadly the current and developing regulatory and technological issues for which HEI could provide significant scientific input. Over the next year HEI will develop, with input from its sponsors and the scientific community, a new five-year plan. Discussion with sponsors will begin this fall at a sponsors meeting, continue in various settings, and then culminate in discussion of a draft strategic plan at HEI's 1999 Annual Conference in May.

Continuing and New Research and Review Initiatives

Ambient Particles

• NMMAPS Study: Work is continuing on the National Morbidity, Mortality, and Air Pollution Study, which is using a U.S.-wide data set to analyze the health effects of several pollutants, including particulate matter, for their relation to respiratory and cardiovascular morbidity and mortality. This study, which will be completed in early 2000, is expected to have other important impacts beyond its results. The use of a national sampling frame for these analyses of morbidity and mortality will provide a new model for surveillance of the health effects of air pollutants, and the analytic approaches to be developed will have widespread application to air pollution studies.
• Epidemiology Reanalysis Project: The reanalysis of data from the Six-Cities and American Cancer Society Studies is actively under way. A report will be submitted to HEI by the end of 1999. The report is expected to contribute not only to a better understanding of the two studies it focuses on, but also to provide recommendations about the design of new studies that would provide better data on the effects of long-term exposure to particulate air pollution. Because of the importance of knowing more about the long-term effects of exposure to particles, HEI would like to fund new research in this area.
• Studies of Populations as Risk and Mechanisms of Action: Experimental and epidemiologic studies from RFA 94-2, Particulate air Pollution and Daily Mortality: Identification of Populations at Risk and Underlying Mechanisms, will be completed over the next year, and reports will be reviewed by the HEI Review Committee in time for inclusion in the next PM criteria document. Five studies under way from RFA 96-1, Mechanisms of Particle Toxicity: Fate and Bioreactivity of Particle-Associated Compounds. Some of these are expected to be completed in time to contribute to the next PM criteria document.
• New PM Studies: Eighteen exposure assessment and health effects studies have been selected for funding from RFA 98-1, Characterization of Exposure to and Assessment of Health Effects of Particulate Matter. To make the most of this research program, we have worked with the investigators to enhance connections between their studies, and with EPA to coordinate our PM research programs. Several are under way at this time, and all will start by the end of the year. The program includes:

4 studies to assess personal exposure of “normal” and potentially sensitive groups living in U.S. cities on the east coast, on the west coast, and in Texas, as well as in two European cities;

a field validations study for a new method that will quantify the acid component of ultrafine particulate matter

2 epidemiologic studies that will investigate the association between certain cardiac events (arrhythmias and nonfatal myocardial infarctions) and changes in ambient concentrations of particulate matter;

3 human controlled-exposure studies that will use similar protocols to compare effects of exposure to ultrafine carbon particles and to concentrated ambient particles in New York City and in the Los Angeles area;

8 experimental studies in animals addressing a number of hypotheses about effects causes by particles and their mechanisms, using different end points, animal models and types of particles, including concentrated ambient particles in New York, Boston, and Detroit.

Several of these studies will provide either final reports or interim reports in time to be reviewed and incorporated into the next PM criteria document.

• Workshop on the Health Effects of Fine Particles: HEI is working with the European Commission to plan a workshop to be held in January 1999 on the health effects of fine particles. The goals of the meeting are to provide a forum for leading researchers from Europe and the U.S. to present and discuss the current status of scientific information on particulate matter, and to identify the scientific questions most relevant to risk assessment for particulate air pollution, including those more relevant to European regulatory needs.

Diesel Exhaust

• Diesel Epidemiology Expert Panel: The expanded use of diesel vehicles had created a need for better scientific information to support risk assessment for diesel exhaust. The Diesel Epidemiology Panel is reviewing the existing epidemiologic studies that have been used to develop risk assessments for diesel exhaust, and the dose-response analyses conducted by the U.S. EPA and the California EPA. The Panel is developing a report that identifies sources of uncertainty and gaps in the existing epidemiologic data base for diesel exhaust, makes recommendations about the usefulness of extending these data sets, and makes recommendations for the design of new studies.
• Diesel Feasibility Studies: From RFA 98-3, Epidemiologic Investigations of Human Populations Exposed to Diesel Engine Emissions, which was issued in May 1998, six one-year studies are under negotiation and are expected to start by the end of this year. Several of these feasibility studies will identify cohorts to study; others will address exposure issues.
• Diesel Research Strategy Workshop: In March 1999, HEI will hold a workshop to bring together epidemiologists, diesel exposure experts, current and potential new sponsors, and Research Committee members in order to learn about the status of current research on the health effects of diesel exhaust. This workshop will help HEI define new epidemiologic research on diesel exhaust, and consider other types of studies that would be useful in understanding better the potential carcinogenic and non-carcinogenic effects of diesel exhaust.

Air Toxics

• Benzene and 1,3-Butadiene Studies: Seven of eight studies funded under RFA 93-1 to improve extrapolation from high levels of exposure to low levels of exposure and across species and to develop biomarkers have been completed and are under review by the HEI Review Committee. These reports will be published in 1999.
• Transitional Epidemiology Studies: Two transitional epidemiology studies are investigating the relation between exposure of subjects to benzene or 1,3-butadiene and the level of biomarkers (including many developed in studies funded by HEI under RFA 93-1) in blood and urine. Subjects in the benzene study are workers in China; subjects in the 1,3-butadiene study are workers in the Czech Republic. Both studies will be completed in 1999.
• New Studies on Personal Exposure to Aldehydes: Studies funded under RFA 97-2, Assessing Personal Exposure to Selected Aldehydes Using Chemical and Biological Techniques, to develop information on human exposure to several aldehydes of potential concern started recently. These studies are evaluating exposure to aldehydes in a sample of the general population, in residents of urban areas, and in workers in diesel-repair facilities, garages, and gas stations. Depending on the outcome of these studies of personal exposure, HEI may consider additional health effects studies of aldehydes in the future.
• Metals Emitted by Motor Vehicles: HEI has been concerned about the potential toxicity of metals used in catalytic converters, as fuel additives, or in other ways in motor vehicles. Although they are used for beneficial purposes, they have the potential of causing other changes in emissions that may increase the toxicity of other agents or may produce toxicity themselves. HEI issued RFPA 98-4 in its October 1998 RFA Book to develop a research program beginning to address these broad concerns.

Oxygenated Fuels and Additives

• Ethers Studies: Studies from a 1995 RFA that are investigating the pharmacokinetics in rats and humans of several ethers used in gasoline (MTBE, ETBE, TAME) will continue through 1998. One report is due late in 1998, and the others in 1999.
• Methanol Research Report: Two reports from the final study in HEI's methanol research program, which investigated behavioral effects in monkeys exposed in utero, are under review and will be published in 1999. One report is on the pharmacokinetics of methanol in the adult animals before and during pregnancy and the effects of methanol on reproductive function; the other is on neurobehavioral effects in the offspring that were exposed in utero.

Ozone and Other Oxidants

• Ozone Research Reports: Reports from two animal studies looking at the role of inflammation in acute and chronic lung injury will be reviewed in the next year.
• Nitric Oxide Study Report: The final report of a study comparing effects of nitric oxide (NO) to those of other oxidants that have been more extensively studied (ozone and nitrogen dioxide) is currently under review by the HEI Review Committee. This study evaluated the extent and location in the lung of injury resulting from repeated inhalation exposures of rats to NO.

Other Areas of Interest.

• Multiple Pollutants: Several ongoing HEI studies are looking at mixtures of pollutants. NMMAPS is looking at ambient particles alone and in combination with other pollutants. Another study in this category is a study of rats exposed to Mexico City air, which has been found to cause nasal lesions in people even after relatively short exposures. In each of these cases, the ultimate goals are to increase our understanding of the roles of individual pollutants and of combinations of pollutants. There is increasing realization about the importance of understanding pollutant interactions, and the HEI Research Committee is keeping that in mind as it develops plans for its research programs.
• New Investigator Award: In its October 1998 RFA book, HEI issued RFA 98-5, the Walter A. Rosenblith New Investigator Award. The purpose of this award is to bring new, creative investigators into active research on the health effects of air pollution.

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