EPA
United States National Center for EPA/600/R-97/132F
Environmental Protection Environmental Assessment January 15,1998
Agency Research Triangle Park, NC 27711
Particulate Matter Research Needs
for Human Health Risk Assessment
To Support Future Reviews of the
National Ambient Air Quality
Standards for Particulate Matter
-------
EPA/600/R-97/132F
January 15,1998
Particulate Matter Research Needs for
Human Health Risk Assessment
To Support Future Reviews of the
National Ambient Air Quality Standards
for Particulate Matter
National Center for Environmental Assessment
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
-------
DISCLAIMER
This document has been reviewed in accordance with U.S. Environmental Protection
Agency policy and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
-------
TABLE OF CONTENTS
Page
Preface ix
Authors, Contributors, and Reviewers xi
1. EXECUTIVE SUMMARY 1
1.1 PURPOSE, SCOPE, AND ORGANIZATION 1
1.2 PRIORITIZATION 4
1.2.1 High-Priority Issues 4
1.2.2 Overarching Concepts 8
1.2.2.1 Interdisciplinary Collaboration 8
1.2.2.2 Inclusive Approach 8
1.2.2.3 International Collaboration 9
1.3 TIMING 9
2. INTRODUCTION 10
2.1 BACKGROUND 10
2.2 RECENT PARTICULATE MATTER NATIONAL AMBIENT AIR
QUALITY STANDARD REVIEW 11
2.3 U.S. ENVIRONMENTAL PROTECTION AGENCY OFFICE OF RESEARCH
AND DEVELOPMENT STRATEGIC RESEARCH PLANNING 12
3. PRIORITIZATION AND TIMING OF RESEARCH NEEDS 15
3.1 SUMMARY OF KEY UNCERTAINTIES AND RESEARCH
RECOMMENDATIONS FROM THE STAFF PAPER 16
3.2 SUMMARY OF RESEARCH QUESTIONS DEVELOPED AT THE
PARTICULATE MATTER RESEARCH NEEDS WORKSHOP 17
3.3 CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE REVIEW 18
3.3.1 Clean Air Scientific Advisory Committee Concern with Causality 18
3.3.2 Research Needs Highlighted in the Clean Air Scientific Advisory
Committee Review Letter 18
3.3.3 Clean Air Scientific Advisory Committee Summary of Highest
Priority Topics 20
3.4 ANALYSIS OF RESEARCH NEEDS IN TERMS OF THE RISK
ASSESSMENT PARADIGM 21
3.5 THE PARTICULATE MATTER HEALTH RESEARCH PROGRAM:
A PUBLIC/PRIVATE PARTNERSHIP 25
3.5.1 Background 25
3.5.2 The Paniculate Matter Health Research Program Workshop 26
3.5.3 Interdisciplinary Needs Emphasized by the Particulate Matter Research
Program Workshop 28
111
-------
TABLE OF CONTENTS
(cont'd)
3.6 EPA STAFF SYNTHESIS AND ANALYSIS 28
3.6.1 Highest Priority Issues 29
3.6.2 Effects of Long-Term Exposure to Particulate Matter 30
3.6.3 Susceptibility, Who and Why? 30
3.6.4 Mechanisms of Biological Response 31.
3.6.5 Key Components 32
3.6.6 Exposure Relationships 33
3.6.7 Exposure-Dose-Response 36
3.6.8 New Techniques and Equipment 38
3.6.9 Other Important Issues 38
3.6.9.1 Effectiveness of Mitigation 38
3.6.9.2 Background Concentrations 39
3.6.9.3 Atmospheric Modeling and Source Characterization 39
3.6.10 Overarching Concepts 40
3.6.10.1 Inclusive Approach 40
3.6.10.2 Interdisciplinary Collaboration 40
3.6.10.3 International Collaboration 41
3.7 TIMING OF RESEARCH TASKS 41
3.7.1 The 5-Year Cycle 41
3.7.2 Tasks To Produce Research Results in Time To Impact the Next Particulate
Matter Air Quality Criteria Document 43
3.7.2.1 Effects of Long-Term Exposure to Particulate Matter 43
3.7.2.2 Susceptibility, Who and Why? 44
3.7.2.3 Mechanisms of Biological Response 44
3.7.2.4 Key Components 45
3.7.3 Research Support Tasks 47
3.7.3.1 Effects of Long-Term Exposure—Epidemiology 47
3.7.3.2 New Tools for Toxicology 48
3.7.3.3 New Tools for Exposure Assessment 49
3.7.4 Long-Term Studies That Need To Be Initiated with Fiscal
Year 1998 Funding 51
3.7.4.1 Research Monitoring Networks 51
4. EPIDEMIOLOGY 53
4.1 BACKGROUND 53
4.2 PARTICULATE MATTER EPIDEMIOLOGY RESEARCH NEEDS 56
4.2.1 Interdisciplinary Planning 56
4.2.2 Incidence of Premature Mortality and Time of Life Lost 57
4.2.3 Public Health Burden of Particulate Matter Exposure 58
4.2.4 Relative Health Effects of Key Attributes of Particulate Matter 59
IV
-------
TABLE OF CONTENTS
(cont'd)
Page
4.2.5 Interactions of Particulate Matter and Gaseous Pollutants 60
4.2.6 Role of Weather and Climate 60
4.2.7 Susceptibility, Who and Why? 61
4.2.8 Effects of Short-Term Exposure 61
4.2.9 Markers of Acute and Chronic Health Effects 62
4.2.10 Exposure-Response Relationship 63
4.2.11 Statistical Analyses of Uncertainty 63
4.2.12 Biomedical Assessment of Origins, Stages, and Progression of
Particulate Matter-Associated Disorders in Humans 65
5. TOXICOLOGY AND DOSIMETRY 65
5.1 BACKGROUND 65
5.2 DETERMINANTS OF INHALED PARTICLE DOSE 68
5.3 DETERMINANTS OF TOXICANT-TARGET INTERACTIONS AND TISSUE
RESPONSE 69
5.3.1 Clearance and Repair 69
5.3.2 Host Susceptibility 70
5.3.3 Host Adaptation to Particulate Matter-Induced Health Effects 75
5.4 PHYSICAL CHARACTERISTICS OF PARTICLES 76
5.5 POTENTIAL CAUSATIVE AGENTS 77
5.5.1 Ambient Aerosol 77
5.5.2 Transition Metals 78
5.5.3 Particulate Matter-Associated Acid 78
5.5.4 Particulate Matter-Associated Organic Compounds 80
5.5.5 Bioaerosols 81
5.6 METHODOLOGICAL ISSUES 82
6. MEASUREMENT, CHARACTERIZATION, AND EXPOSURE 84
6.1 PARTICULATE MATTER RESEARCH PROGRAM WORKSHOP 84
6.1.1 Definitions and Conceptual Framework 85
6.1.1.1 Exposure 85
6.1.1.2 Particulate Matter/Gases 85
6.1.1.3 Framework 85
6.1.1.4 Sensitive Populations 86
6.1.2 Research Questions 86
6.2 PERSONAL EXPOSURE: CONCENTRATION/EXPOSURE
RELATIONSHIPS 87
6.3 CHARACTERIZATION 89
6.3.1 Measurement/Monitoring Programs 89
6.3.2 Size Distribution 89
-------
TABLE OF CONTENTS
(cont'd)
6.3.3 Ultrafine Particles 90
6.3.4 Indoor Particulate Matter 90
6.3.5 Reactions of Dissolved Substances in Particles 90
6.3.6 Collection and Characterization of Particulate Matter for
Toxicological Studies 91
6.4 POPULATION EXPOSURE 92
6.4.1 Exposure Models 93
6.4.2 Concentration Measurements 93
6.4.3 Population Exposure Studies 93
6.4.4 Estimation of Concentration and Exposure Parameters for
Epidemiologic Studies 93
6.4.4.1 Temporal Variability in Concentration 93
6.4.4.2 Spatial Variability 94
6.4.4.3 Long-Duration Measurements 94
6.4.5 Integration of Regulatory and Research Monitoring Programs 95
6.5 MEASUREMENT/MONITORING TECHNIQUES 96
6.5.1 Measurement of Fine-Mode Particles and Coarse-Mode Particles as
Separate Pollutants 96
6.5.2 New Measurement Techniques for Particulate Matter Parameters
for Which Existing Measurement Techniques Are Inadequate 96
6.5.3 Measurement of the Semivolatile Components of Particulate Matter 99
6.5.4 Continuous and Long-Time-Interval Samplers Need To Be Developed
for Particulate Matter Parameters for Which Existing Measurement
Techniques Are Adequate 100
6.5.5 Time Resolution of Particulate Matter Measurements 101
6.5.6 Monitoring/Measurement Situations 102
6.5.7 Precision of Measurement Techniques 102
6.5.8 Measurement of PM2 5 for Determining Compliance Status 102
6.6 AMBIENT CHARACTERIZATION AND MODELING 103
6.6.1 Air Quality Models for Aerosols 103
6.6.2 Emission Inventories 105
6.6.3 Source Apportionment of Ambient Particulate Matter 106
6.6.3.1 Source Apportionment Techniques 107
6.6.3.2 Composition of Primary Emissions 107
6.6.3.3 Time Series of Source Category Contributions 108
6.6.4 Secondary Organic Particulate Matter Formation 108
6.7 BACKGROUND CONTRIBUTIONS TO PARTICULATE MATTER
CONCENTRATIONS 109
6.8 INDIRECT HEALTH EFFECTS RELATED TO CHANGES IN PARTICULATE
MATTER LEVELS Ill
VI
-------
TABLE OF CONTENTS
(cont'd)
Page
6.9 GENERAL PRINCIPLES 112
APPENDIXES
Appendix A: Summary of Key Uncertainties and Research Recommendations A-l
Appendix B: U.S. Environmental Protection Agency Particulate Matter Research
Needs Workshop B-l
Appendix C: Clean Air Scientific Advisory Committee Panel for Review of
Particulate Matter Research Needs for Health Risk Assessment C-l
Appendix D: Clean Air Scientific Advisory Committee Evaluation of Research
Needs for the Particulate Matter National Ambient Air Quality
Standards D-l
VII
-------
PREFACE
This document was prepared by the Research Triangle Park, NC, Division of U.S.
Environmental Protection Agency's (EPA's) National Center for Environmental Assessment,
with assistance from scientists from other EPA Office of Research and Development laboratories
(the National Exposure Research Laboratory and the National Health and Environmental Effects
Research Laboratory) and non-EPA expert consultants. Several earlier drafts of the document
also were reviewed by experts from academia, various federal and state government units,
nongovernmental health and environmental organizations, and private industry. An earlier
external review draft was reviewed in public meetings by the EPA's Clean Air Scientific
Advisory Committee. The National Center for Environmental Assessment acknowledges with
appreciation the valuable contributions made by the many authors, contributors, and reviewers,
as well as the diligence of its staff and contractors in the preparation of this document.
IX
-------
AUTHORS, CONTRIBUTORS, AND REVIEWERS
U.S. ENVIRONMENTAL PROTECTION AGENCY PERSONNEL
National Center for Environmental Assessment (NCEA) Project Team
NCEA Scientific Staff Authors
Dr. William E. Wilson—Project Manager, Senior Atmospheric Research Advisor,
National Center for Environmental Assessment RTP Division (MD-52), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711
Dr. Lester D. Grant—Director, National Center for Environmental Assessment RTP Division
Dr. Lawrence J. Folinsbee—Chief, Environmental Media Assessment Group
Dr. Robert Chapman—Medical Officer
Ms. Annie M. Jarabek—Toxicologist
Dr. Joseph P. Pinto—Physical Scientist
NCEA Scientific Staff Contributors
Dr. Allan Marcus—Statistician
Dr. Dennis Kotchmar—Medical Officer
Ms. Beverly Comfort—Health Scientist
Mr. William Ewald—Health Scientist
NCEA Technical Support Staff
Mr. Douglas B. Fennell—Technical Information Specialist
Ms. Emily R. Lee—Management Analyst
Ms. Diane H. Ray—Program Analyst
Ms. Eleanor Speh—Office Manager, Environmental Media Assessment Branch
xi
-------
AUTHORS, CONTRIBUTORS, AND REVIEWERS
(cont'd)
Ms. Donna Wicker—Administrative Officer
Mr. Richard Wilson—Clerk
U.S. EPA National Exposure Research Laboratory (NERL)
Dr. Judith Graham—Associate Director for Health
Dr. James S. Vickery—Assistant Director for AIR
Linda S. Sheldon—Physical Scientist
Lawrence H. Cox—Senior Statistician
U.S. EPA National Health and Environmental Effects Research Laboratory (NHEERL)
Dr. John J. Vandenberg—Assistant Director for AIR
Dr. Daniel L. Costa—Chief, Pulmonary Toxicology Branch
Dr. Kevin Dreher—Research Chemist
U.S. EPA Office of Air Quality Planning and Standards (OAQPS)
John D. Bachmann—Associate Director
Karen M. Martin—Group Leader, Health Effects and Standards Group (HESG)
Mary Ross—Epidemiologist, HESG
XII
-------
AUTHORS, CONTRIBUTORS, AND REVIEWERS
(cont'd)
OTHER CONTRIBUTORS AND REVIEWERS
Several earlier drafts of this PM health risk research needs document were reviewed by
experts from academia, various federal and state government units, nongovernmental health and
environmental organizations, and private industry, both from within the United States and
internationally. These include invited participants in the EPA-sponsored workshops held in
September 1996 and November 1997 in Research Triangle Park and Durham, NC, respectively.
Also, an external review draft of this document was released for public comment and review by
the Clean Air Scientific Advisory Committee (CASAC) of EPA's Science Advisory Board at
a public meeting held in Chapel Hill, NC, in December 1996. Significant revisions were made in
successive drafts of the document in response to the above workshops discussions and CASAC
review, leading to the present final version of the document. Many experts (too numerous to list
here) participating in the above-noted workshops and CASAC review made notable contributions
to discussions at the workshops and to the CASAC review, as well as to resulting summary
materials drawn on as input to the preparation of the present document. The names and
affiliations of the many workshop participants and CASAC reviewers are identified in
Appendices B and C of this document and in the appendix of the November 1997 EPA
Workshop Report (EPA/600/R-98/007).
Xlll
-------
1. EXECUTIVE SUMMARY
1.1 PURPOSE, SCOPE, AND ORGANIZATION
The U.S. Clean Air Act (CAA) requires the Administrator of the U.S Environmental
Protection Agency (EPA) to review the air quality criteria and National Ambient Air Quality
Standards (NAAQS) for each criteria pollutant every 5 years. As part of this process, it is
customary to prepare a document that identifies important uncertainties in the existing database
and presents and prioritizes research needs that should be addressed to improve the scientific
bases for future reviews of the NAAQS. Such research needs documents do not present a
research plan or program. The primary reason for the examination of research needs is to guide
the EPA national research laboratories, which undertake and support research, in developing and
justifying research plans and programs.
This report documents EPA's efforts to identify and prioritize research needs specifically
related to assessment of the risk to human health from exposure to airborne particulate matter
(PM) of ambient origin. PM, as used in the report, applies broadly to all possible components,
subcomponents, or classes of PM, not just the current indicators for PM standards (PM2 5 and
PM10). The information discussed herein should serve as a useful guide to assist EPA and other
organizations that support PM-health-related research in developing and coordinating their PM
research programs. It is hoped that this endeavor will assist in promoting cooperation among the
wide range of scientific disciplines involved in PM-health research and will assist funding
agencies in achieving and sustaining such cooperation. Neither the research needs, nor the
research approaches mentioned under specific research needs, are intended to serve as requests
for proposals. However, this document should provide useful inputs to organizations in planning
both intermural programs and extramural procurement.
This report focuses on research needed to support future reviews of the NAAQS for PM.
It does not address research needs related to implementing PM air quality standards, determining
compliance, or determination of effective control techniques to comply with such standards.
Research needs on areas of common interest in both reviewing and attaining the NAAQS for PM
such as monitoring and modeling ambient PM and source identification, are discussed here in
part. A more complete discussion of implementation research needs and their relation to health
risk related exposure research can be found in documents such as EPA's Research Strategy for
-------
PM, and the NARSTO-A White Paper and Charter Plan for Aerosols. It also does not address
research needs related to occupational exposure. However, this document is not limited to
research that will be performed or funded by EPA. Other federal and state government agencies
and other stakeholders (e.g., academia; industry; agencies of other countries, the European
Union, and the United Nations; nongovernmental organizations in the United States and other
countries) are expected to contribute to research efforts needed to address the PM research needs
discussed in this document.
The research needs and their prioritization are based primarily on (1) U.S. EPA's PM air
quality criteria document (AQCD), entitled^//" Quality Criteria for Paniculate Matter
(EPA/600/P-95/001aF, bF, and cF, April 1996), and the associated EPA policy assessment (staff
paper), entitled Review of the National Ambient Air Quality Standards for Particulate Matter:
Policy Assessment of Scientific and Technical Information (EPA-452/R-96-013, July 1996);
(2) the EPA-sponsored PM Research Needs Workshop held in September 1996 to review and
discuss the first draft of this document; (3) public review of the first external review draft of this
document by the Clean Air Science Advisory Committee (CASAC) of EPA's Science Advisory
Board (SAB); (4) review and synthesis by EPA scientific staff from the National Center for
Environmental Assessment (NCEA), the National Health and Environmental Effects Research
Laboratory (NHEERL), and the National Exposure Research Laboratory (NERL); and
(5) discussions during the EPA-sponsored Particulate Matter Health Research Program
Workshop held in November 1997. A more extensive description of the NAAQS review
process, EPA's research planning process, and the September 1996 PM Research Needs
Workshop, which provided the first external review of this document, is provided in Section 2.
More information on the November 1997 Particulate Matter Health Research Program Workshop
is given Section 3.7 and Section 6.1. A separate EPA report on the November workshop is
available (EPA/600/R-98/007)
Based on the extensive assessment of the latest available scientific information in the EPA
PM AQCD and staff paper, the EPA Administrator concluded that revision of the PM NAAQS
was appropriate and necessary. Of particular importance, the available data strongly suggest that
adverse health consequences are associated with exposure to the fine-mode fraction of PM
(generally indexed by PM2 5) or to one or more of its constituents. In its closure letter on the
-------
staff paper, CAS AC endorsed the option of establishing new PM NAAQS as a means to reduce
risk associated with exposure to ambient fine particles and the use of PM 2.s as an indicator for
the new NAAQS.
However, the nature and severity of human health effects caused by ambient PM have not
yet been fully characterized. As discussed in the PM AQCD and staff paper, the available
database remains subject to important uncertainty regarding
• community exposure to anthropogenic ambient PM and its many constituents,
• the pathogenic role of PM in relation to other air pollutants,
• the relative pathogenic roles of the numerous size fractions and chemical entities that constitute
the overall PM complex,
• the biological mechanisms through which ambient PM may exert adverse health effects,
• the shapes of PM exposure-dose-response relationships for various health endpoints,
• the spatial and temporal generalizability of current epidemiologic findings on PM,
• the subpopulation groups most at risk of adverse PM effects, and
• the host factors that determine susceptibility to adverse PM effects.
This document is intended to identify future research directions that will best serve to
resolve such scientific uncertainties.
This document focuses on PM research needed to improve human health risk assessment,
which includes both health-related research and pertinent atmospheric science, monitoring,
modeling, and exposure research as well. However, not all areas of PM-related scientific
uncertainty and not all needs for future PM-related research and development bear directly on
human health risk assessment. For example, much further scientific effort also is required in
development of control strategies, control technology, implementation plans, and monitoring and
modeling for compliance. This document does not address these other types of PM risk
management research needs. The importance of risk management for EPA/Office of Research
and Development's (ORD's) overall PM research planning is recognized but dealt with
elsewhere, such as in EPA's Research Strategy for PM and in EPA/ORD's contribution to the
NARSTO-A Charter Plan for Aerosols.
Also, welfare effects, caused by or related to PM (e.g., visibility degradation, soiling, acid
deposition, UV-B transmission, climate change), although important, are to be addressed mainly
-------
by other research programs in ORD or other federal agencies. Indeed, much of the emission
inventory, chemical processes, and atmospheric transport research important for PM modeling is
being conducted under EPA's ozone and acid deposition programs. Only modifications or
augmentations of those programs, as required to address PM health risk assessment needs, are
discussed in this document.
This document contains chapters on research needs in each of three broadly defined key
areas: (1) epidemiology; (2) toxicology/dosimetry; (3) and measurement, characterization, and
exposure. Epidemiology is addressed first because it is primarily epidemiologic findings that
have led to recently increased concern for the potential adverse public health effects of ambient
PM exposure and reconsideration of PM standards. The toxicology section, which includes
laboratory animal and human toxicology, discusses research needs to improve information on
biological mechanisms underlying PM health effects, the effects of specific components of PM,
and, through dosimetry, the relationships of laboratory animal exposure to human exposure and
the differences in exposure-dose relationships between healthy and diseased subjects.
The section on measurement, characterization, and exposure focuses on research needs to
improve monitoring, modeling, and exposure information for use in planning, conducting, and
interpreting epidemiologic and toxicological studies and to provide exposure assessment data for
risk characterization through monitoring and modeling.
1.2 PRIORITIZATION
1.2.1 High-Priority Issues
A chapter on prioritization proceeds the detailed description of research needs. Research
issues from the OAQPS staff paper, research questions from the September 1996 PM workshop,
and prioritization comments from CACAC are summarized. The prioritization comments of
CASAC are discussed in more detail. Priority needs and issues are then integrated and discussed
in terms of timing to provide information for future reviews of PM NAAQS. A brief discussion
of the November 1997 PM Health Research Program Workshop is given and the key
interdisciplinary needs discussed at the Workshop are summarized.
EPA concludes that the following issues merit highest priority.
-------
Effects of long-term exposure to PM. The health effects of long-term exposure to PM of
ambient origin are not as well understood as the effects of short-term exposure, even though
the long-term effects may be as important or more important than short-term effects. Greater
attention should be placed on resolving uncertainties about the potential effects of long-term
exposure to PM, such as life shortening, progressive disease, and increased susceptibility to
acute effects. The relative contributions of short-term spikes and cumulative exposure need to
be determined.
Susceptibility. The difficulty in reproducing in laboratory animal exposure studies, even at
high concentrations, the acute effect of major concern, (i.e., sudden death within a few days of
an acute exposure to relatively low concentrations) suggests that there must be something
special either about the ambient aerosol or the people responding to it. It is important to
determine what subpopulation groups are at most risk from short- and long-term exposure and
what host factors influence the susceptibility. The CASAC panel stated that, "Research
providing a better understanding of personal exposure, and especially of individuals thought to
be most susceptible, was given high priority."
Biological mechanisms. An understanding of the mechanisms by which PM could contribute
to life shortening, daily mortality, and morbidity is needed to understand the relative
importance and the interactions among the various components of PM and the interactions of
gaseous and paniculate pollutants. The CASAC panel agreed that laboratory and clinical
research exploring potential mechanisms of response to PM were among the highest priorities.
Greatest value was placed on research exploring associations between physical-chemical PM
characteristics and response pathways and potency. High value was also placed on studies
exploring the existence and nature of responses at environmentally relevant doses of PM.
Key components. Exposure to fine particle mass is associated statistically with health effects.
However, there is concern that one or more components of PM may be more toxic than others
or that certain physical-chemical characteristics may be more important than mass. It is
possible that different characteristics or components are associated with different biological
responses. Information to identify key components in causing health effects could come from
toxicology or epidemiology. The CASAC panel stated that, "Priority should be given to
epidemiological studies of either type which provide the ability to examine linkages between
-------
health effects and personal exposures to physical-chemical subclasses of PM." It is important
to determine the relative pathogenic roles of the numerous size fractions, chemical entities, and
physical-chemical characteristics that constitute the overall PM complex. Before this can be
done, additional measurement studies are needed to describe the physical parameters and
identify and characterize the chemical components. It is also important to determine the extent
to which PM causes health effects independently of other pollutants, the extent to which PM
acts as a carrier to transport normally gaseous material into the lung, and the extent to which
gaseous pollutants interact with PM in causing effects, and the role of other potentially
confounding effects such as local weather.
Exposure relationships. Epidemiologic studies depend on the assumption that there is a
relationship between ambient concentrations measured at one community air pollution monitor
(or the average of several) and the average personal exposure in the community to pollution of
ambient origin. It is also assumed that the statistical association between ambient
concentrations and health effects is not confounded by personal exposure to PM from
non-ambient sources. More work is needed to establish the variability of the distribution of
PM concentrations across a community in order to relate concentrations at a community
monitor to concentrations outside a home, office, etc., for mass and chemical composition of
components of various PM size classes. Studies are needed to measure personal exposure and
to determine if a sufficiently strong relationship exits between personal exposure and central
site ambient measurements so that the latter can be used as surrogate measure of personal
exposure. Since it is personal exposure to particles of ambient origin that is of concern in
setting NAAQS, such studies should partition total personal exposure into its four components,
exposure to particles of ambient origin while outdoors, exposure while indoors to ambient
particles which have infiltrated indoors, exposure to particles generated indoors, and exposure
to particles generated by personal activities (see Figure 3-2).
Once the relationship between ambient concentrations and the concentration of ambient
particles indoors has been established, personal exposure to ambient particles can be modeled
using activity pattern data (time in various microenvironments). With the addition of time
with varying ventilatory patterns and knowledge of regional lung dosimetry, it may also be
possible to begin to model dose, especially differences in dose between normal and potentially
-------
susceptible populations. The distribution of population exposure to ambient particles is also
needed for the exposure assessment component of risk analysis. The distribution of ambient
PM concentrations, needed to calculate the distribution of population exposure to ambient
particles, may be inferred from ambient measurements provided the spatial and temporal
characteristics of PM concentrations are properly represented. The distribution of ambient PM
concentrations might also be estimated using advanced modeling techniques, taking advantage
of knowledge gained from the research described above, and incorporating these findings along
with ambient measurements.
Exposure-dose-response. Before a risk assessment can be performed, it is necessary to know
the relationship between exposure, dose, and response. The shapes of the exposure-dose-
response curves may vary for short- and long-term exposure, for various health end points, for
various susceptible groups, and for various aspects (size, composition, etc.) of the PM.
Exposure-dose-response information may be obtained from human clinical and epidemiologic
studies. However, it appears likely that much useful information will be obtained from studies
using animal models of susceptible humans. Extrapolation of exposure-dose-response from
susceptible animals to susceptible humans will require an improved understanding of particle
deposition and clearance in abnormal lungs (e.g., individuals with preexisting pulmonary
disease) or other likely susceptible population groups (the elderly, young infants and children,
etc.).
New techniques and equipment. This is not considered a separate issue but is highlighted to
hasten interdisciplinary progress. New techniques and equipment are needed to generate
ambient or simulated ambient particles for laboratory exposure studies, to diagnose the effects
of exposure to air pollutants for toxicology and epidemiology, and to make more precise and
accurate measurements of PM mass, components, and parameters. Especially important is the
development of continuous measurements and batch sampling techniques that remove particle-
bound water, but retain semivolatile components such as ammonium nitrate and semivolatile
organic compounds and that provide a better separation of fine and coarse particles.
-------
1.2.2 Overarching Concepts
1.2.2.1 Interdisciplinary Collaboration
The September 1996 PM Research Needs Workshop, the CAS AC review, and the
Paniculate Matter Health Research Program Workshop identified interdisciplinary interactions,
as initiated at the September 1996 workshop, as essential to research progress in PM human
health risk assessment. The September 1996 workshop attendees recommended the following:
Planning Research Need—Expand the interdisciplinary discussion (involving epidemiology;
toxicology/dosimetry; and measurement, characterization, and exposure) conducted at this
workshop in order to better define and prioritize the research needs and especially to identify'
multidisciplinary approaches and programs to address the research needs. This need for
interdisciplinary discussion was endorsed by CAS AC and the November 1997 Workshop.
Accordingly, EPA expects to sponsor, organize, or participate in additional interdisciplinary
workshops to define specific research programs.
1.2.2.2 Inclusive Approach
Particulate matter is a complex mixture of condensed phases, gases, and materials that
transfer from one phase to another (semivolatile components). Gas-phase pollutants, in addition
to being present as gases, may be absorbed on or dissolved in particles. All of these components
interact physically and chemically and may affect the body in interactive ways. Therefore,
nonvolatile PM, semivolatile PM, and gas-phase pollutants may contribute collectively to health
effects. The potential importance of all three components of air pollution should be considered
in the design ofcontrolled-exposure studies and in the planning of measurements of ambient
pollution for epidemiological studies. To the extent possible, all these components should be
included in some studies.
EPA regulates each air pollutant as a separate entity. However, EPA is moving toward
consideration of the effects and control of air pollution in an integrated manner. Although this
document focuses on PM, it emphasizes the need for inclusion of other air pollutants in PM
research.
-------
1.2.2.3 International Collaboration
The need for collaboration in international efforts by U.S. scientists and U.S.-supported
researchers was also noted by the CAS AC panel. As an example, the panel recommended
collaboration of EPA and its supported researchers in international efforts such as the "Air
Pollution and Health: European Project."
Different countries currently use a variety of PM indicators. These differ in upper and
lower cut point, in conditioning and other processes that determines loss or retention of
semivolatile PM, and in what component or parameter of PM actually determines the
measurement (e.g., British smoke measures elemental carbon). EPA staff considers the
international harmonization of PM indicators to be a high priority need.
1.3 TIMING
The Clean Air Act schedule for future reviews, and for preparation of future U.S. EPA PM
criteria documents, which provide the scientific basis upon which review of the U.S. PM
NAAQS depends, dictates certain timing requirements. The next cycle for review of the U.S.
PM NAAQS begins in FY98 with a final decision, either to reaffirm or revise of the existing
standards, being due by July 2002. To meet the July 2002 promulgation date, the next EPA PM
criteria document must be completed by the fall of 2000. Research discussed in the PM criteria
document must be published (or accepted for publication) by the time of the final review of the
new PM criteria document by CASAC. Thus, in order to be accepted for publication in 2000,
any new research to be considered in the next PM NAAQS decision should be submitted to
journals by early 2000. Therefore, this document identifies research that could produce
meaningful results in time to be included in the next PM criteria document, support tasks to
develop tools needed for future research programs, and longer term studies. Many of the longer
term research studies will need to be initiated by FY99 in order to provide research results for
future PM criteria documents beyond the next one to be completed in 2000. For example,
chronic epidemiology studies must begin right away to allow time for data collection for the
subsequent NAAQS review cycle. Also, it is likely that identification of key components will
require several years of iterative research by health and exposure scientists. Given the
-------
requirement for iteration, the foundation for future research directions must be laid now if key
uncertainties are to be resolved by the time of the subsequent review.
2. INTRODUCTION
2.1 BACKGROUND
The U.S. CAA requires the EPA Administrator to set NAAQS for certain widespread major
air pollutants. These "criteria pollutants" currently include PM, ozone and other photochemical
oxidants; nitrogen oxides, carbon monoxide (CO), sulfur oxides (SOX), and lead. Primary
NAAQS are set to protect the public health with an adequate margin of safety. In general, this
standard setting involves judgments on such issues as what indicators, averaging times, forms,
and levels of standards are appropriate to protect against adverse health effects. This also
involves the identification of sensitive groups within the population who may respond to
exposures to ambient concentrations of the given pollutant. Secondary NAAQS are to be set to
protect against adverse welfare effects (e.g., vegetation or ecosystem damage, materials damage,
soiling, impacts on visibility and climate, etc.) associated with ambient air pollutant levels. The
NAAQS for a given pollutant, and the criteria on which they are based, are to be reviewed
periodically (at least every 5 years) and, as appropriate, revised.
Decisions on setting or revising the NAAQS for a given pollutant are based on air quality
criteria derived from evaluation of the latest available scientific information useful to determine
the nature and extent of health and welfare effects associated with exposures to ambient
concentrations of a given "criteria" air pollutant (such as PM or others listed above). Relevant
scientific information is evaluated in ambient AQCD's prepared by NCEA, a component of
EPA's scientific arm, ORD. Key scientific findings from the criteria document for a given
pollutant are drawn on and summarized, together with other information (e.g., exposure and risk
estimates), in a staff paper prepared by the Office of Air Quality Planning and Standards
(OAQPS) within EPA's Office of Air and Radiation (OAR), EPA's air policy office. The
OAQPS staff paper for the pollutant also sets forth policy options for the EPA Administrator to
consider in proposing possible retention or revision of the pertinent primary and/or secondary
NAAQS. Development of the AQCD and the staff paper for a given pollutant includes extensive
10
-------
opportunities for public comment, as well as peer review by CASAC of EPA's SAB, as part of
the process ultimately leading to proposal and final promulgation of NAAQS decisions.
In the course of assessing scientific information during the periodic review of air quality
criteria and NAAQS for any given criteria air pollutant, various data gaps and uncertainties are
often identified, which, if addressed by research, could lead to notable improvements in the
scientific knowledge available to support future periodic review of air quality criteria and
NAAQS for that pollutant. It has been found useful, once the AQCD and staff paper have been
completed to support a given NAAQS review, for EPA to prepare a document characterizing
important uncertainties and research needs that should be addressed to improve the scientific
bases for future NAAQS decisions. Such research needs documents identify the broad range of
research desirable to provide improved bases for subsequent NAAQS decision making; serve as
communication vehicles for informing the public and general scientific community as to what the
needs are; and provide valuable inputs to research and budget planning by EPA's ORD, other
EPA units, and other governmental and nongovernmental organizations in the United States and
internationally. Taken together with comparable research needs documents for PM NAAQS
implementation, a comprehensive research strategy for PM NAAQS review and attainment can
be constructed.
2.2. RECENT PARTICULATE MATTER NAAQS REVIEW
The EPA recently has completed its periodic review of the PM NAAQS. The NAAQS
review involved preparation of a new PM AQCD (completed April 1996) and the associated
PM staff paper (July 1996). Both of these documents underwent extensive internal and external
review, including public comment and review by CASAC. The criteria document, Air Quality
Criteria for Paniculate Matter (EPA-600/P-95/001aF), prepared by NCEA, is a thorough review
and assessment of the state of current scientific knowledge on PM. The staff paper, Review of
the National Ambient Air Quality Standards for Particulate Matter: Policy Assessment of
Scientific and Technical Information (EPA-452YR.-96-013), prepared by OAQPS, drew on
information in the PM AQCD and made recommendations that formed the bases for EPA
decisions on the PM NAAQS.
11
-------
The recently completed PM AQCD concluded that epidemiologic studies conducted since
the previous NAAQS review indicated a consistent statistical association between adverse health
effects and PM concentrations, even at levels below the NAAQS for PM10 (i.e., 150 ug/m3 [24 h]
and 50 ug/m3 [annual average]), and recommended that fine particles and coarse particles be
considered as separate pollutants. The staff paper also concluded that the consistency and
coherence of the epidemiologic evidence justified revision of the PM NAAQS and that
protection of the public health could be accomplished best by both maintaining the above PM10
standards, to protect against exposure to coarse particles, and establishing standards for fine
particles, using PM2 5 as an indicator. Both the staff paper and the PM AQCD discuss
uncertainties in the database.
Following publication of EPA's proposal to revise the PM standards and extensive public
comment on the proposal, the EPA Administrator, on July 16, 1997, revised the PM NAAQS by
promulgating standards for fine particles, with PM2 5 as the indicator. The annual PM2 5
standard will be met when the 3-year average of the annual arithmetic mean PM2 5
concentrations, from single or multiple community-oriented monitors, is less than or equal to
15 ug/m3. The 24-h PM2 5 standard will be met when the 98th percentile of 24-h PM2 5
concentrations per year (averaged over 3 years) at the population-oriented monitoring site with
the highest measured value in an area is less than or equal to 65 ug/m3. EPA has retained the
annual PM10 standard of 50 ug/m3 and the 24-h PM10 standard of 150 ug/m3 to protect against
exposure to coarse particles. However, the form of the 24-h PM10 standard was revised from one
expected exceedance to the 99th percentile, averaged over 3 years. EPA established this suite of
PM standards with 24-h and annual averaging times to protect against effects from both short-
and long-term exposure identified in community epidemiology studies.
2.3 EPA ORD STRATEGIC RESEARCH PLANNING
The EPA ORD currently is planning future research on ambient airborne PM. ORD's
overall PM research planning includes the following components: (1) The Strategic Plan for the
Office of Research and Development (EPA/600/R-96/059), issued May 1996; (2) this document
on PM health risk research needs; (3) a separate ORD PM Research Program Strategy developed
12
-------
jointly by participating centers and laboratories of EPA/ORD (NHEERL MS-97-019); and
(4) participation in the North American Research Strategy for Tropospheric Ozone and Aerosols
(NARSTO-A) partnership.
The ORD strategic plan (first component) identifies several high-priority theme areas to
guide ORD research efforts during the next 5 years or so, including research on airborne particles
as one key theme area. The following excerpt from the ORD strategic plan indicates the high
level of public health concern about air pollution related health effects and the high level of
importance that ORD attaches to future PM-related research:
"Recent publications in the scientific literature indicate that exposure to particulate matter
poses a high potential hitman health risk. At the same time, however, there is a high
degree of uncertainty about the size and composition of the particles that may be
responsible for these effects, the biological mechanisms of action, and the dose-response
relationships at low levels of exposure. In addition, control costs are potentially very high.
For all these reasons, this area is of high priority to EPA's OAR and of high priority for
ORD's research agenda."
The present PM health research needs document (second component) is designed to serve
as a basis for development of PM-related health and exposure research plans by EPA and other
organizations. It identifies major scientific uncertainties in the existing PM database, and it
describes the types of research that will best serve to resolve these uncertainties. In this
document, primary emphasis is placed on uncertainties identified in the course of preparation of
the recently published PM AQCD and PM staff paper, and their review by CAS AC.
Consideration also is given to results presented at recent scientific meetings and workshops that
included discussion of PM research needs and approaches. The first draft of this document,
dated August 8, 1996, was reviewed within EPA by staff of OAQPS and ORD laboratories (i.e.,
the National Exposure Research Laboratory [NERL], the National Health and Environmental
Effects Research Laboratory [NHEERL], and the National Risk Management Research
Laboratory [NRMRL]). The next version incorporated revisions made following the September
4 to 6, 1996, PM Research Needs Workshop involving EPA in-house staff, external experts, and
other interested parties (stakeholders). An external review draft of this document, dated
October 25, 1996, was circulated for public comment and underwent peer review by CASAC at a
13
-------
public meeting in December 1996. A November 1997 draft incorporated changes based on
public comments, review comments from individual CASAC members, and the consensus letter
from CASAC to the EPA Administrator characterizing the committee's overall
recommendations. The present version contains additional modifications based on the November
1997 PM Research Program Workshop discussions.
The third component in ORD's PM research planning process is the ORE) PM Research
Program Strategy (PM-RPS), developed in parallel with preparation of the present research needs
document. The PM-RPS focuses on research that relates directly to EPA's mission, reflects
activities in EPA's ongoing extramural program and the expertise and interests of EPA
intramural scientists, and is compatible with the research budget for ORD's laboratories. Thus,
the PM-RPS is not intended to cover all necessary PM-related future research identified in this
document. A draft of the ORD PM-RPS was reviewed earlier, internally by ORD's Science
Council and externally by CASAC, at the same public meeting at which CASAC reviewed the
October 25, 1996, version of this research needs document.
The fourth component of ORD's PM research planning is its participation in the North
American Research Strategy for Tropospheric Ozone and Aerosols (NARSTO-A) partnership.
This joint public/private research organization plans and coordinates that implementation
research in the United States, Canada and Mexico associated with attaining national standards for
ozone, and is in the process of expanding its charter and strategic execution plan to include PM.
Ozone and PM share many of the same precursor sources and much the same atmospheric
chemistry and physics. Research on the source emissions, ambient measurement methods and
monitoring, atmospheric chemistry and meteorology, and modeling of aerosols and its precursors
are being included in a NARSTO-A Charter Plan. Exposure research needs as they relate to
ambient, indoor and personal measurments and methods will be a subject of special attention.
The exposure issue is recognized as the bridge between the PM atmospheric science research of
NARSTO-A and the PM health risk research presented in this document. The NARSTO-A
White Paper, November, 1997 lists the principle research needs for aerosols within the
atmospheric sciences and source emissions areas. The White Paper and its research agenda have
been the subject of two national workshops (the NARSTO-PM workshop, September, 1997, and
the Annual NARSTO Symposium November, 1997). A profile of the state of Aerosol science
14
-------
which will serve as background a NARSTO-A Charter Plan is in preparation (due for release
January, 1998). The Charter Plan, identifying prioritized and timelined research tasks to meet
the needs of the White Paper, will be prepared in time to guide FY99 investments by member
organizations.
3. PRIORITIZATION AND TIMING OF RESEARCH NEEDS
Identification of uncertainties in the information available for review of a specific NAAQS
and the prioritization of research needs to address those uncertainties is a continuing process.
In the case of the recent PM NAAQS review, this process began with development of the
PM AQCD. Important uncertainties were explicitly documented in Section VII-E, Summary of
Key Uncertainties and Research Recommendations, of the staff paper (reproduced in
Appendix A). This process continued with development of a prior review draft of this document,
and review and discussion of that draft at the EPA-sponsored PM Research Needs Workshop
held at Research Triangle Park in September 1996. During the PM workshop, a set of research
questions were developed by the participants and were included in the external review draft of
this document issued September 25, 1996. More information on the workshop is given in
Appendix B, including the research questions and a list of participants. Although the staff paper
and the external review draft both discussed uncertainties and research questions, neither
prioritized the PM research needs. In December 1996, CAS AC reviewed the external review
draft of this document in a public review meeting and provided comments to EPA with regard to
their recommendations for prioritization of PM research needs (CASAC panel members are
listed in Appendix C, and the CASAC panel letter to the administrator is reproduced in
Appendix D). In the following section, research needs from the staff paper, the PM Research
Needs Workshop, and the CASAC review are summarized. Finally, a synthesis and analysis is
provided by NCEA staff. Interdisciplinary research needs, highlighted at the November 1997
PM Research Program Workshop also are presented.
15
-------
3.1 SUMMARY OF KEY UNCERTAINTIES AND RESEARCH
RECOMMENDATIONS FROM THE STAFF PAPER
The 1996 OAQPS PM staff paper stated: "Staff believes it is important to emphasize the
unusually large uncertainties associated with establishing standards for PM relative to other
single-component pollutants for which NAAQS have been set. The PM AQCD and this staff
paper note throughout a number of unanswered questions and uncertainties that remain in the
scientific evidence and analyses as well as the importance of ongoing research to address these
issues." The important uncertainties and related OAQPS staff paper research recommendations
are summarized below (the full text is presented in Appendix A).
(1) Lack of demonstrated mechanisms that would explain the mortality and morbidity effects
associated with PM at ambient levels reported in the epidemiologic literature.
(2) Uncertainties introduced by measurement error and inadequacies in ambient monitors.
Uncertainties in PM exposure estimates introduced by using central site monitoring data to
estimate population exposure to PM.
(3) Are effects attributed to PM exposure confounded by other pollutants commonly occurring
in ambient air?
(4) What specific components or physical properties of fine particles are associated with the
reported effects of PM?
(5) Uncertainties in the shape of the ambient concentration-response relationship.
(6) Unaddressed confounders and methodological uncertainties inherent in epidemiological
studies of long-term PM exposures.
(7) The extent to which lifespans are being shortened.
(8) Annual and daily background concentrations.
(9) Lack of animal, clinical, and community studies of the effects associated with exposure to
coarse fraction particles.
16
-------
3.2 SUMMARY OF RESEARCH QUESTIONS DEVELOPED AT THE
PARTICULATE MATTER RESEARCH NEEDS WORKSHOP
The questions are summarized below (not in order of priority; the full text is presented in
Appendix C).
(1) How can acute, time-series epidemiological studies be evaluated to determine if the effects
of particles are real and causal?
(2) Can the amount of chronic morbidity and life shortening due to PM exposure be better
quantified through additional studies of the chronic effects of long-term PM exposure?
(3) What sensitive subpopulations are most affected by short- and long-term PM exposures,
and what are the important host factors putting them at risk?
(4) What is the spectrum of acute and chronic health outcomes of PM exposure, and by which
biological mechanisms do specific chemical components or size fractions of PM cause or
promote specific health effects?
(5) How can dosimetry models be improved to contribute to evaluation of findings in
epidemiology, controlled human exposure studies, and laboratory animal studies and to
improve insight on potential mechanisms of action?
(6) What are the characteristics of ambient particulate matter in different regions of the
United States?
(7) What is the relationship between PM concentrations at ambient monitoring sites and
personal exposure to PM of ambient origin?
(8) How can a standardized, widespread, research-grade ambient PM monitoring network best
be achieved to provide improved air quality data for PM exposure and epidemiologic
studies?
(9) How can the spatial and temporal variability in ambient concentrations be better
characterized?
(10) Can the nonanthropogenic background and other noncontrollable background
concentrations be estimated for use in risk assessments?
17
-------
3.3 CASAC REVIEW
The October 25, 1996, the external review draft of this document was reviewed during
a December 1996, public meeting of CASAC. The draft ORD PM Research Program Strategy
(NHEERL MS-97-019) also was reviewed by CASAC at the same meeting. Comments from
members of CASAC and expert consultants to CASAC (which together make up the CASAC
panel) were provided to EPA in the March 12, 1997, letter "Evaluation of Research Needs for the
Particulate Matter National Ambient Air Quality Standards" transmitted to EPA Administrator
Carol M. Browner by Joseph L. Mauderly, Chair, and George T. Wolff, Immediate Past Chair,
on behalf of CASAC (EPA-SAB-CASAC-LTR-97-004). Portions of that letter relevant to
overall prioritization are quoted below (the entire letter is reproduced in Appendix D).
3.3.1 CASAC Concern with Causality
EPA concluded in the PM AQCD and the PM staff paper that the coherence and
congruence of the available epidemiologic evidence warranted the conclusion that low-level
ambient PM concentrations/exposures likely were causally related to human mortality and
morbidity (e.g., as indexed by increased hospital admissions, respiratory symptoms, lung
function decrements, etc.). However, as noted by some public comments on the PM NAAQS
proposals and in the course of the CASAC review of the earlier draft of this research needs
document, issues continue to be raised with regard to the need to substantiate further the direct
causality of PM, and especially PM 2.5, in the health effects observed by epidemiology.
Although the CASAC panel agreed that present evidence warrants concern and most members
support implementation of a fine particle standard, the panel also alluded to aspects regarding the
causality of PM2 5 and noted some important related uncertainties (e.g., concerning the
relationship between area monitoring data and personal exposure, the suitability of PM2 5 as the
best surrogate for the causative agents, etc.).
3.3.2 Research Needs Highlighted in the CASAC Review Letter
"There should be greater emphasis on resolving uncertainties about the long-term effects of
PM. Additional attention should be focused on long-term effects, such as life shortening or
progressive disease. Accompanying data are needed on long-term PM levels, trends, and
18
-------
characteristics, as well as levels of other pollutants." There was consensus that epidemiological
research on links between long-term exposure to PM and life shortening and other long-term
health effects was among the highest priorities. Research on short-term effects should focus on
refining the understanding of exposure-dose-effects relationships. "The Panel felt that there was
little need for documenting additional examples of associations between short-term increases in
PM and health effects using the same approaches as in the past. There is a need for new data sets
providing improved understandings of the individuals incurring short-term effects and the
physical-chemical nature of the PM to which they were exposed, and for alternate data analysis
techniques." Priority should be given to epidemiological studies of any type that provide the
ability to examine linkages between health effects and personal exposures to physical-chemical
subclasses of PM. When known, the nature and dose-responses relationship of the effects of
individual compounds in pure form might provide a point of reference useful for judging the
plausibility of effects estimated for those compounds encountered as constituents of PM.
"There was also consensus that laboratory and clinical research exploring potential
mechanisms of response to PM was among the highest priorities. Greatest value was placed on
research exploring associations between physical-chemical PM characteristics and response
pathways and potency. High value was also placed on studies exploring the existence and nature
of responses at environmentally-relevant doses of PM.
"Research providing a better understanding of personal exposure, and especially of
individuals thought to be most susceptible, was given high priority."
"The panel noted a lack of emphasis on retrospective research to determine the
effectiveness with which reductions in PM and other pollutants reduce adverse health effects ....
The downward trend in ambient PM should provide opportunities to demonstrate an associated
health benefit, and it might also be possible to follow implementation of specific source controls
in some locations with studies to detect improvements in health indices thought to be associated
with PM .... Demonstration of an association between reductions of PM and adverse health
outcomes would support causality.
"The efforts of atmospheric scientists, laboratory researchers, clinical researchers, and
epidemiologists will be required to resolve several of the uncertainties, and consideration should
be given to providing a framework for integrating these efforts. There should be mention of the
19
-------
need for research training with a focus on cross-disciplinary perspectives and collaborations.
Collaboration of EPA and its supported researchers in international efforts, for example, with the
'Air Pollution and Health: European Project', should also be emphasized."
Some panel members also noted the need for an improved understanding of PM
concentrations that might be considered "background", or representative of broader rural and
semirural areas than present monitoring sites allow.
"Beyond the above priorities, opinion was mixed and defied straightforward summary.
There was mixed enthusiasm for atmospheric modeling and characterization of source emissions.
Studies of the dosimetry of inhaled particles in normal subjects was not given strong support,
although it was agreed that present dosimetry models could benefit from a better understanding
of particle deposition and clearance in abnormal lungs. There were mixed views regarding the
priority of developing tools for market-based control approaches. Some members favored
conducting research to improve market-based approaches. Others warned that not all PM2 5
species are equipotent and that such approaches must be informed by an understanding of the
relative contributions of different physical-chemical classes of PM within size ranges."
3.3.3 CASAC Summary of Highest Priority Topics
The CASAC panel highlighted the following issues as being of highest priority:
• effects of long-term exposures and relative contributions of short-term spikes and cumulative
exposures to long-term health outcomes;
• mechanisms by which PM could contribute to life shortening, daily mortality, and morbidity;
• linkages between PM data from area monitors and personal exposures;
• PM classes and physical-chemical characteristics associated with different health effects; and
• the extent to which PM causes health effects independently of other pollutants.
The next level of priority (for health risk assessment purposes) can be assigned to
• determination of background concentrations,
• effectiveness of pollution control in reducing adverse health effects,
• atmospheric modeling,
• source characterization, and
• market-based controls.
20
-------
The CASAC Panel also emphasized the following important concepts:
interdisciplinary collaboration,
inclusive approach to include nonvolatile PM, semivolatile PM, and gas phase pollutants in
exposure studies and epidemiological exposure assessments, and
international cooperation.
3.4 ANALYSIS OF RESEARCH NEEDS IN TERMS OF THE RISK
ASSESSMENT PARADIGM
In their review letter, CASAC urged NCEA staff to analyze PM research needs in terms of
the risk assessment paradigm. This has proven to be a useful exercise because it provides a
different perspective on needed research and priorities. The risk assessment paradigm, shown
schematically in Figure 3-1, involves several steps. The first, hazard identification, involves the
recognition of a hazard and an effect, or group of effects, resulting from exposure to that hazard.
Once a hazard has been identified, exposure assessment studies can be initiated to determine the
extent of population exposure to that hazard. Once a hazard/effect combination has been
identified, dose-response studies, or more accurately exposure-dose-response studies, need to be
undertaken. The combination of population exposure (exposure assessment) and exposure-dose-
response information (dose response) provides an indication of the severity of the risk (risk
characterization). If the risk is sufficiently severe to warrant mitigation, the various steps in risk
management can be undertaken.
It may be useful to compare the risk assessment process for a less complex criteria
pollutant, CO, with that of PM. Carbon monoxide is a simple, specific chemical compound.
Ambient PM is a complex mixture of many different classes of pollutants containing thousands
of different chemical species that may have different biological properties and whose toxicity
may depend on size and other physical properties as well as chemical composition. Thus, in the
case of ambient PM, a large number of potential hazards need to be examined, as indicated in
Table 3-1.
Carbon monoxide is readily absorbed from the lungs into the blood where it forms an
identifiable marker of exposure, carboxyhemoglobin. The primary biological response to CO
21
-------
Dose Response
Assessment
Hazard
Identification
Risk
Characterization
Figure 3-1. Risk Assessment Paradigm
Table 3-1. Potential PM Hazards Expressed as Parameters, PM Fractions, or Chemical
Components
Parameter
Size Fraction (abbreviation)
Chemical Components
Number
Surface area
Volume
Mass
Total suspended particles
Thoracic particles (PM10)
Coarse fraction (PM10_2 5)
Fine fraction (PM2 5)
Fine-mode (PM] 0)
Accumulation mode
Ultrafine particles
Hydrogen ion
Transition metals
Sulfate
Nitrate
Elemental carbon
Organic compounds
is to reduce the availability of oxygen to body tissues, leading to a range of effects from reduced
exercise duration because of chest pain (angina), in individuals with coronary artery disease at
low levels of exposure, to coma and death, in healthy individuals at higher levels of exposure.
22
-------
There is no comparable biomarker of exposure for PM, and the biological mechanisms
underlying pathophysiological responses to low concentrations of ambient PM are not well
understood. The various components of ambient PM undoubtedly cause a variety of different
biological responses by a variety of mechanisms and may vary considerably in their potency.
As is shown in Table 3-2, a number of effects have been associated with short-term exposure to
PM and a number of additional effects may potentially be associated with long-term exposure to
PM. The lack of information on effects of long-term exposure, coupled with the possible
significance as suggested by studies of the association of chronic PM exposure with increased
rates of mortality, justifies the high priority given by CASAC to exposure to long-term effects
ofPM.
Table 3-2. Health Effects Potentially Related to Exposure to Ambient PM
Effects Associated with Short-Term Exposure to PM
• Premature Mortality
• Aggravation of respiratory and cardiovascular disease (as indicated by increases in):
- Hospital admissions
- Emergency room visits
- School Absences
- Work loss days
- Restricted activity days
• Changes in lung function
• Increased respiratory symptoms
• Changes to lung tissues
• Altered respiratory defense mechanisms
Effects Potentially Related to Long-Term Exposure to PM
• Increase in mortality rate
• Increase in prevalence of
- Chronic obstructive pulmonary disease
- Bronchitis
- Asthma
• Permanent decrease in lung function or a reduction in maximum lung function expected
with growth
• Changes in lung ultrastructure
23
-------
This comparison of PM with CO emphasizes the importance of susceptibility. Occupational
standards are set to protect healthy adults from exposures lasting no more than 8 h a day, 40 h a
week. NAAQS, as required by the Clean Air Act, must protect susceptible or sensitive
population groups from exposures lasting up to 24 h a day. In the case of CO, a major
susceptible population group identified as being highly sensitive to CO is individuals with
preexisting angina due to coronary artery disease. As shown in Table 3-3, there are a number of
population groups potentially susceptible to PM and a variety of possible reasons for their
susceptibility or sensitivity.
Table 3-3. Sensitive Population Groups
Individuals with respiratory disease • Children
Individuals with cardiovascular disease • Infants
Elderly individuals • Individuals with asthma
EPA has identified fine particles as a hazard associated with a variety of effects ranging
from biological changes to increased mortality (Table 3-2). However, there is concern that fine
particle mass is not the specific hazard or the most appropriate indicator of the effects. Other
parameters, size fractions, or chemical components (as shown in Table 3-1) may be better
indicators of the biological effects. Specific chemical components of PM may have varying
types of biological effects and potency. Thus, much additional work remains to be done in the
hazard identification phase to determine the various hazard/effect combinations, and the most
susceptible population groups. It is also important to determine whether PM mass, some mixture
of PM components (perhaps in conjunction with gas-phase pollutants), or some specific PM
parameters or components are responsible for the observed adverse effects on PM.
This analysis in terms of risk assessment also emphasizes the importance of dose response
(exposure-dose-response) and exposure assessment.
Much of the hazard identification research will use laboratory animals, including laboratory
animal models of human diseases. Extrapolation of animal dose-response to human dose-
response will require additional knowledge of the human to animal scaling functions, especially
24
-------
for humans with cardiopulmonary impairment and animal models of such impairments. It will
be useful to express dose relative to a number of biological parameters (e.g., particle mass,
number, or component concentration per macrophage, per epithelial cell, per bronchial surface
area, etc.).
Currently, the exposure-dose-response for exposure to fine particles is expressed only as a
relationship between ambient mass concentrations and health outcome responses. Therefore, the
ambient concentration of PM2 5 is the most useful exposure metric that can be used in risk
characterization. However, in the future information on exposure-dose-response for personal
exposure to ambient PM and to more specific indicators of PM such as PM)( the coarse fraction
of PM10, particle composition parameters, and particle number or other particle characteristics
should become available. Therefore, within the context of exposure assessment, research needs
include improved measurement tools and improved information on the relationships between
outdoor particles from ambient sources, ambient particles that have infiltrated indoors, and
particles generated by indoor sources, as well as more information on ambient PM
concentrations.
3.5 THE PARTICULATE MATTER HEALTH RESEARCH PROGRAM:
A PUBLIC/PRIVATE PARTNERSHIP
3.5.1 Background
to*
EPA's FY 1998 appropriation, as reported out by the Congressional Conference
Committee, includes a substantial increase in the budget for PM research, and an expectation that
EPA will move forward immediately in its PM research program. Further, it identifies an
important role for the National Academy of Sciences (NAS) in developing and monitoring
implementation of a comprehensive, prioritized, near- and long-term particulate matter research
plan, working in close consultation with representatives from many public and private sector
organizations. This recommendation for an integrated research plan " is meant to build on the
research which has already been planned, is underway, or has been completed by EPA, NIEHS,
NAS, HEI, and numerous other public and private entities, and will rely on the hard work and
continued good will of all interested parties."
25
-------
The NAS is now preparing to develop the near-term research plan, which is to be available
by the end of March 1998. In this context, "near-term" refers to research that can be initiated and
completed in time to be considered in the next criteria document development and NAAQS
review process. The NAS is also to prepare a longer term research plan by the November 1998.
Research unlikely to be completed in time to be considered in the next criteria document process
is referred to as "long-term". There may be instances where research needs to begin soon,
although the effort will be completed in the longer term.
The intent of Congress, as described in the Congressional Record (October 6, 1997) is that
the research plan will be the principal guideline for the EPA's particulate matter research
program over the next several years. EPA is charged with implementing the plan, including
conduct of appropriate peer review and distribution of intramural and extramural funds, in a
manner that assures that research as determined in the plan will proceed in an orderly and timely
fashion, and according to the priority basis outlined by NAS. The plan also affects other
agencies, with Congress expecting EPA and other federal agencies to review their ongoing PM
research activities and, where appropriate, refocus activities so as to be consistent with the NAS
plan.
3.5.2 The Particulate Matter Health Research Program Workshop
Considering the intent of Congress, and previous interactions with CAS AC, EPA has
chosen to take a broad-based approach to PM research planning and program development. This
approach extends participation in PM research planning to the private sector, similar in concept
to an approach used successfully for planning tropospheric ozone research. Accordingly, a 3-day
workshop was held November 17 through 19, 1997, to bring together experts and organizational
representatives from both the public and private sectors to discuss and prioritize PM health-
related research needs (i.e., those research activities important to improve the basis for future
decisions regarding the PM NAAQS).
The workshop format included a series of presentations and discussions in plenary session
on Day 1. On Day 2 and at the outset of Day 3, breakout groups were used to discuss in more
detail issues related to three major research areas: (1) epidemiology, (2) toxicology, and
26
-------
(3) exposure. Plenary presentations on Day 3 were used to summarize the findings of the
breakout groups. A cross-group discussion closed the meeting.
The efforts to coordinate health effects research on PM are complemented by parallel
expansion of the North American Research Strategy for Tropospheric Ozone (NARSTO)
partnership to include a focus on research issues related to implementation of the PM standard.
NARSTO represents a model cooperative effort in the areas of atmospheric processes and risk
management. The relationship between NARSTO and the new health effects research program
also were discussed at the workshop, with close communication ties anticipated.
The purpose of the Particulate Matter Health Research Program Workshop was threefold:
(1) to initiate formation of a public/private research program on particulate matter health effects
research;
(2) to stimulate development of an inventory of current PM research efforts; and
(3) to facilitate further coordination of efforts among research organizations.
Key objectives of the workshop include the identification of concrete recommendations
regarding
• near-term research priorities (including near-term research needed to address longer term
priorities) and
• longer term research priorities.
Three objectives were stated for the breakout groups:
(1) reassess the information and research needs for PM, using the November 1, 1997, draft of
this document (EPA PM Research Needs for Health Risk Assessment to Support Future
Reviews of the National Ambient Air Quality Standards for Particulate Matter) as a
strawman;
(2) establish a priority list of what might be accomplished in the next 2 to 3 years (short-term)
and likewise develop a priority list for 5 to 7 years (long-term); and
(3) develop a coordinated, multidisciplined approach to the needs as prioritized; one which
capitalizes on organization strengths, fosters collaboration, and minimizes redundancy.
27
-------
3.5.3 Interdisciplinary Needs Emphasized by the Particulate Matter Health
Research Program Workshop
One interesting aspect of the Particulate Matter Health Research Program Workshop was
the growing recognition of interdisciplinary needs (i.e., needs expressed by two or all three of the
breakout groups or a need, expressed by one group, that would have to be supplied by members
of another group). Five interdisciplinary needs were quite clear.
(1) Susceptibility. All three groups emphasized the importance of identifying and studying
susceptible populations.
(2) Monitoring. Both the epidemiology and exposure groups emphasized the need for a
commitment to provide sustained, long-term and extensive measurements at a few sites.
These measurements are needed to provide data for epidemiologic studies and to provide
a platform for more intensive studies.
(3) Personal Exposure. Both the epidemiology and exposure groups identified the relationship
between ambient concentrations and personal exposure to ambient particles as a key area of
investigation.
(4) Source Apportionment. Both the epidemiology and toxicology groups identified a need for
source information, lexicologists want to study exposure to PM from specific sources.
Epidemiologists want to look for associations between variation in frequency of health
effects and variations in ambient concentrations caused by specific sources.
(5) Characterization. The toxicology group identified a need that should be addressed by the
exposure group. The PM supplied to laboratory subjects exposed to concentrated
accumulation mode aerosol should be characterized. Large samples should be collected
concurrently and made available to the scientific community for other types of studies.
Concentrators used by different groups need to be characterized to determine if they provide
identical samples in terms of size cuts and transmission of reactive gaseous pollutants.
3.6 EPA STAFF SYNTHESIS AND ANALYSIS
EPA staff concurred with CASAC's recommendations for highest priority topics but felt
that two additional topics should be added to the highest priority category. These are
28
-------
• susceptibility, who and why; and
• exposure-dose-response.
3.6.1 Highest Priority Issues
The foregoing analysis of inputs on research needs from knowledgeable, interested parties
(including EPA staff) shows remarkable concurrence on substantive issues, albeit with some
small differences in wording and focus. Therefore, EPA staff recommends the adoption of the
following highest priority topics.
• effects of long-term exposure to PM;
• susceptibility, who and why;
• mechanisms of biological response;
• key components;
• exposure relationships; and
• exposure-dose-response.
The next level of priority for health risk assessment purposes (high instead of highest) can
be assigned to
• determination of background concentrations,
• effectiveness of mitigation,
• atmospheric modeling, and
• source characterization.
There was agreement on the importance of the following overarching concepts in guiding
PM research:
• interdisciplinary collaboration,
• inclusive approach, and
• international collaboration.
The above issues and concepts are discussed briefly below. Detailed discussions of
individual research needs are given in the sections on epidemiology; toxicology and dosimetry;
and measurement, characterization, and exposure.
29
-------
3.6.2 Effects of Long-Term Exposure to Particulate Matter
The CASAC Panel felt that "there should be greater emphasis on resolving uncertainties
about the long-term effects of PM. Additional attention should be focused on long-term effects,
such as life shortening or progressive disease. Accompanying data are needed on long-term
PM levels, trends, and characteristics, as well as levels of other pollutants." The panel also stated
that it was of high priority to investigate the "effects of long-term exposures and the relative
contributions of short-term spikes and cumulative exposures to long-term health outcomes."
The staff paper called attention to "Unaddressed confounders and methodological uncertainties
inherent in epidemiological studies of long-term PM exposures." The 1996 Workshop asked,
"Can the amount of chronic morbidity and life shortening due to PM exposure be better
quantified through additional studies of the chronic effects of long-term PM exposure?" The
1997 Workshop concurred in the importance of understanding the effects of long-term exposure.
Chronic epidemiologic studies are difficult, expensive, and require a long time to complete.
However, the few available studies suggest chronic effects may be greater than acute effects.
Lung damage resulting from chronic exposure also may cause people to be more susceptible to
acute effects. More work is needed to determine the effects of long-term PM exposure, to
differentiate these effects from those caused by short-term exposure, and to determine if the
effects of long-term exposure increase susceptibility to effects from short-term exposure.
Research that may produce near-term results include studies with susceptible as well as normal
population groups; determination of PM exposure for existing cohorts from other types of
epidemiologic studies; and chronic animal studies using laboratory-generated particles, simulated
smog with photochemically and combustion-generated particles, and concentrated ambient
particles.
3.6.3 Susceptibility, Who and Why?
The 1996 Workshop asked, "What sensitive subpopulations are most affected by short term
and long term PM exposures and what are the important host factors putting them at risk?"
NCEA-RTP staff identified as key uncertainties, "the subpopulation groups most at risk of
adverse PM effects, and the host factors that determine susceptibility to adverse PM effects."
CASAC stated, "Research providing a better understanding of personal exposure, and especially
30
-------
of individuals thought to be most susceptible, was given high priority." The analysis of priorities
in terms of the risk assessment paradigm brought out the importance of identifying susceptible
groups. All three disciplinary break-out groups at the 1997 Workshop emphasized the
importance of identifying and studying susceptible groups. In view of these concerns, the
identification of susceptible population groups and determination of the factors that cause them
to be more susceptible are included in the highest priority research needs.
Potentially sensitive population groups include, but are not limited to, infants, the elderly,
persons with preexisting chronic lung or heart disease, and persons with acute lung disease.
Susceptibility may result from the age of the lung (immature or elderly), acute or chronic lung
disease, or increased deposition in certain areas of diseased lungs. Other important susceptibility
factors, discussed by the toxicology breakout group at the 1997 workshop included broadly
defined cardiopulmonary disease states, genetic/congenic attributes of the host, and personal
lifestyle influences (e.g., diet, activity, etc.). The toxicology breakout group also pointed out the
importance of developing and refining animal models of susceptibility states or factors and
suggested considering the utility of newer transgenic approaches.
3.6.4 Mechanisms of Biological Response
The staff paper identified as an important uncertainty the "Lack of demonstrated
mechanisms that would explain the mortality and morbidity effects associated with PM at
ambient levels reported in the epidemiologic literature." The 1996 Workshop asked, "What is
the spectrum of acute and chronic health outcomes of PM exposure and by which biological
mechanism(s) do specific chemical components or size fractions of PM cause or promote specific
health effects?" The 1997 Workshop also gave high priority to studies of mechanisms of
biological response.
The CASAC panel also felt it was of high priority to investigate "mechanisms by which
PM could contribute to life shortening, daily mortality, and morbidity." The panel stated, "There
was also consensus that laboratory and clinical research exploring potential mechanisms of
response to PM was among the highest priorities. Greatest value was placed on research
exploring associations between physical-chemical PM characteristics and response pathways and
potency. High value was also placed on studies exploring the existence and nature of responses
31
-------
at environmentally-relevant doses of PM." At the time the PM AQCD was prepared, some
inflammatory effects of particles and the effects of acid aerosol on clearance rates were known.
However, no biological mechanism to account for the sudden mortality observed in
epidemiologic studies had been demonstrated. Since then, results of studies using laboratory
animal models of human lung diseases and other studies using concentrated suspended ambient
particles have suggested possible mechanisms. Toxicological and dosimetric studies, using
human subjects, laboratory animal, and cultured cells, continue to be needed to identify the
biological mechanisms that cause or lead to acute and chronic health effects. Mechanisms of
increased susceptibility, including determinants of dosimetry and response, should be explored,
including associations between physicochemical PM characteristics and response pathways and
potency. Of special interest is to investigate how the lung can communicate with other body
organ systems including studies of cardiovascular effects of inhaled particles as a possible
mechanism to account for acute mortality from PM.
3.6.5 Key Components
Toxicologic and epidemiologic studies, coupled with air measurments, are needed to
determine if the adverse health effects attributed to fine PM result specifically from fine PM
mass, to the overall mixture of air pollutants, or to one or several components that have special
toxic properties, either individually or in specific combinations or mixtures. This problem of
specifying the key component or components and the problem of identifying the key component
by epidemiology was address by all groups. The staff paper asked, "Are effects attributed to PM
exposure confounded by other pollutants commonly occurring in ambient air? What specific
components and/or physical properties of fine particles are associated with the reported effects of
PM." The 1996 Workshop asked, "What is the spectrum of acute and chronic health outcomes of
PM exposure and by which biological mechanism(s) do specific chemical components or size
fractions of PM cause or promote specific health effects?" The NCEA-RTP staff referred to
uncertainty regarding "the relative pathogenic roles of the numerous size fractions and chemical
entities that constitute the overall PM complex." The CAS AC summary of highest priority
topics listed "PM classes and physical-chemical characteristics associated with different health
effects; and the extent to which PM causes health effects independently of other pollutants." The
32
-------
1997 Workshop also gave high importance to determining which attributes of PM are responsible
for health effects.
Measurement studies are needed to thoroughly characterize the size-distribution and other
physical properties and the chemical composition of particles by size and source. This
information can be used to guide toxicological and epidemiologic studies. The results of those
can then be a guide for what attributes of PM need more detailed characterization. Toxicologic
studies addressing effects of various PM parameters (number, surface area, volume, and mass)
and using individual components, mixtures of components, simulated ambient particles, and real
ambient particles will be needed to address this issue. New epidemiological studies with detailed
and accurate measurements of the concentration of individual components of PM, more realistic
indices of exposure, and better identification of the people suffering short-term effects also may
provide insight into this problem.
The issue of whether fine-mode particles differ in toxicity as a function of size or
composition was raised in specific CAS AC comments: "Do particles of varied size from PMi 5
downward have equal potency per unit mass (i.e., health risk per ug per m3)? Are all PM2 5
particles found in ambient air equally potent in producing toxic effects irrespective of their
chemical composition? The promulgation of the PM2 5 NAAQS is based on the assumption that
all particles in the PM2 5 size fraction are equally toxic irrespective of their size or chemical
composition. This issue must be more rigorously evaluated before billions of dollars are spent
controlling all particle sources."
This issue also was posed in other specific CASAC comments: "Particulate matter is
a complex mixture of condensed phases, gases, and materials that transfer from one phase to the
other. We need to emphasize ... that a variety of the components could be responsible for the
observed effects and that it is unlikely that there is a single causative agent for the health effects."
3.6.6 Exposure Relationships
The staff paper identified "Uncertainties introduced by measurement error in ambient
monitors and by use of central monitors to estimate population exposure." It also recognized a
need for a better characterization of the relationships between personal exposure and
outdoor/indoor air quality. The 1996 Workshop asked several questions related to exposure:
33
-------
"What are the characteristics of ambient paniculate matter in different U.S. regions? What is the
relationship between ambient PM concentration and personal exposure to PM? How can a
standardized, widespread, research-grade ambient PM monitoring network best be achieved to
provide improved air quality data for PM exposure and epidemiologic studies? Can we better
characterize the spatial and temporal variability in exposure?" NCEA-RTP staff identified
uncertainty regarding "community exposure to anthropogenic ambient PM and its many
constituents." The 1997 Workshop also expressed concern with measuring and modeling
personal exposure and with the relationship between ambient concentrations and personal
exposure to particles of ambient origin.
A person's exposure to pollutants can be divided into four categories: (1) exposure to
ambient pollutants while outdoors; (2) exposure, while indoors, to pollutants of ambient origin
that have infiltrated indoors; (3) exposure, while indoors, to indoor-generated pollutants; and
(4) exposure, indoors or outdoors, to pollutants generated specifically by that person's activities,
sometimes called the personal cloud. These four exposure categories are shown schematically in
Figure 3-2. Personal exposure to particles of ambient origin, the combination of categories 1
and 2, is of most interest to EPA. Almost all community epidemiologic studies use ambient
3bncentrations, measured at one community site or an average of a few sites, as a surrogate for
community or personal exposure to ambient pollutants. Very little information is available on
the relationship between the indoor concentration of indoor-generated PM relative to ambient
PM that has infiltrated indoors.
The low correlations found between outdoor and personal concentrations led EPA, as
described in Chapter 7 of the PM AQCD, to conclude that the concentrations of indoor-generated
PM would also be poorly correlated with concentrations of ambient PM. Therefore, it would not
be likely that exposure to indoor-generated particles would be a confounder in the variations in
health effects found to be associated statistically with variations in ambient PM concentrations.
However, concerns about the relationships among ambient, ambient-infiltrated-indoors,
indoor-generated PM, and personal activity PM, as expressed in the CAS AC review of the
external review draft of this document and public comments on the proposal for revised PM
NAAQS, indicate the need for more study. In most studies, the ambient/personal or
ambient/indoor ratios have been measured for several people or homes but only for 1 or 2 days
34
-------
Indoor Sources
(cooking, cleaning)
Total Personal PM
>J Exposure \*'
r**- • -*^\
Personal Sources
(smoking, pets)
Outdoor-Source PM
which penetrates
indoors
Outdoor-Source PM
while outdoors
Personal Exposure to
Ambient PM
Outdoor-Source PM
which penetrates
indoors
Outdoor-Source PM
while outdoors
Figure 3-2. Schematic showing the four categories of PM exposure contributing to total
personal PM exposure and the two categories contributing to personal
exposure to PM of ambient origin.
per person per home. Studies are needed that differentiate the contributions of indoor-generated
and outdoor-infiltrated PM to indoor PM concentrations. Studies also are needed that measure
ambient/indoor ratios for the same house (or ambient/personal ratios for the same person) serially
over longer periods. Studies that can determine independently the various exposure categories
that make up total personal exposure are needed to establish the relationships between the
various exposure categories and between the exposure categories and health effects.
35
-------
It also may be possible to use models to estimate, for a community, the average personal
exposure to ambient PM (or to ambient plus indoor generated PM) and use this parameter,
instead of ambient concentration or personal exposure measurements, in acute or chronic
epidemiologic studies. In order to do this, more information will be needed on ambient,
ambient-infiltrated, and indoor-generated PM for a variety of indoor environments; on the
exposure activity patterns (time outdoors and in various indoor environments) of individuals; and
of construction, meteorological, and ventilation parameters that influence building air exchange
rates. Additional field studies will be needed to define the relationship between ambient
concentration and the four components of personal exposure, to develop models, and to evaluate
models.
Improvements in monitoring tools and data analysis techniques are needed to better
characterize the detailed physical-chemical nature of the PM; to define the spatial distribution of
PM components across a community; and to determine the relationships between ambient
concentration, personal exposure to ambient PM, personal exposure to indoor-generated PM, and
personal activity PM. New research monitoring networks are needed to obtain the PM
concentration data required for exposure indices for chronic and acute epidemiologic studies.
The exposure indices could be concentration 4s a surrogate for exposure or other estimates of
exposure based on personal exposure models. The research networks should include
measurement methods that accurately measure semivolatile PM components and sampling
techniques that better separate fine and coarse particles. Hourly measurements of ambient PM
and specific components are needed to determine if peak or daily concentrations are most
important. For studies of effects of long-term exposure it may be cost effective to use samplers
that integrate for a week to a month.
3.6.7 Exposure-Dose-Response
NCEA staff identified as an important uncertainty "the shapes of the PM exposure-dose-
response relationships for various health endpoints." The staff paper specified "Uncertainties in
the shape of the (ambient) concentrations-response relationship." CAS AC stated "Research on
short-term effects should focus on refining our understanding of exposure-dose-effects
relationships." Because dose response is one component of the risk assessment paradigm, the
36
-------
determination of the exposure-dose-response relationships are included in the highest priority
topics.
Toxicology and dosimetry studies of both humans and animals will be required to
characterize the exposure-dose-response relationship for PM. In this report, dosimetry is defined
as characterizing the determining factors along the entire exposure-dose-response continuum.
Thus, it involves consideration of not only what fraction of ambient PM is inhaled and deposited,
but also how the deposited material is cleared (e.g., dissolution or mucociliary transport) and
what the target cells and effector relationships are that control damage and its repair. Thus,
differences in susceptibility may be caused by differences in unit dose per unit exposure or
differences in response (sensitivity) or both. Understanding these factors will contribute to more
accurately characterizing acute and chronic health effect. Such investigations include controlled
exposures of humans and laboratory animals to PM or its various constituents; in vitro studies of
the mechanisms of particle-cell interactions; and physical and mathematical modeling of PM
deposition, distribution, clearance, and retention.
Much of the understanding of exposure-dose-response must come from studies of
laboratory animals. Therefore, improvements are needed in the ability to relate exposure-dose-
response both in normal animals and in animals with impaired lungs and both to normal humans
and to humans with abnormal lungs. Although CASAC did not give strong support to studies of
dosimetry of inhaled particles in normal subjects, "it was agreed that present dosimetry models
could benefit from a better understanding of particle deposition and clearance in abnormal
lungs." To improve the linkage between exposure and response for PM, the factors (both
physicochemical and biological) that determine inhaled particle dose, toxicant-target interactions,
and tissue response must be understood. Differences in susceptibility can result from factors
influencing regional deposition and retention of particles, toxicant-target interactions, or host
sensitivity (conditions or characteristics of the host organism that alter or enhance tissue
response). Characterization of the variability inherent in these determinants will assist in
describing the uncertainty in the extrapolation of internal dose across species and from healthy
subjects to populations predicted to be at risk. Thus, research to improve understanding of
particle deposition and clearance in abnormal lungs (e.g., individuals with preexisting pulmonary
disease and laboratory animal models of human pulmonary disease) or other likely susceptible
37
-------
population groups (the elderly, young infants and children, etc.) is of highest priority. Additional
studies of the deposition of ultrafme particles also are needed.
3.6.8 New Techniques and Equipment
In order to address these highest priority topics adequately, improvements are needed in the
techniques and equipment available. In some cases the lack of these techniques and equipment
limits progress. New technology and equipment is not listed as separate highest priority need.
Rather, these needs are discussed in the three disciplinary chapters. In many cases, these
techniques will be developed as part of ongoing research programs. However, highlighting their
need may hasten progress since in some cases techniques needed by one discipline may be
developed by workers in another discipline.
New techniques are needed to generate particles for toxicology exposure studies, especially
concentrated ambient particles in the ultrafme and coarse particle size ranges (equipment is in
use for concentrating accumulation-mode particles) and simulated ambient particles in the
ultrafine and accumulation modes. Sensitive, but less invasive techniques, are needed for
diagnosing the effects of exposure to air pollutants for use by both toxicologists and
epidemiologists. Better techniques and equipment are needed for exposure studies and research
measurements of PM concentrations. It is important that new studies of PM concentrations use
methods that separate fine and coarse particles; collect and measure ammonium nitrate, wood
smoke particles, and other semivolatile components; and exclude particle-bound water from the
particle mass measurement. New techniques are needed to differentiate the four components of
personal exposure.
3.6.9 Other Important Issues
EPA concurs with the CASAC panel in assigning the following issues to the next level of
priority.
3.6.9.1 Effectiveness of Mitigation
The CASAC panel further noted "a lack of emphasis on retrospective research to determine
the effectiveness with which reductions in PM and other pollutants reduce adverse health effects.
38
-------
Many of the data cited as demonstrating the health effects of current concern were collected 10 to
15 years ago. The downward trend in ambient PM should provide opportunities to demonstrate
an associated health benefit, and it might also be possible to follow implementation of specific
source controls in some locations with studies to detect improvements in health indices thought
to be associated with PM." The panel appreciated the difficulty, pointed out by EPA staff
members, of detecting reductions in risks associated with reductions of PM in view of their
probable small magnitude and numerous confounding factors, but also noted that it is these
health risks that, in the presence of confounding influences and other uncertainties, gave rise to
the PM NAAQS changes. They further noted that "demonstration of an association between
reductions of PM and adverse health outcomes would support causality."
3.6.9.2 Background Concentrations
Some CAS AC members noted the need for an improved understanding of PM
concentrations that might be considered "background" or representative of broader rural or
semirural areas than present monitoring sites allow.
3.6.9.3 Atmospheric Modeling and Source Characterization
The CASAC panel expressed mixed enthusiasm for atmospheric modeling and
characterization of source emissions. Some members, whose focus was on that research related
to risk assessment and NAAQS review, saw atmospheric modeling to assist with exposure
analysis in unmonitored regions and source characterization to assist in preparation of aerosol
samples for lexicological study as being of some importance. Members who saw it serving these
purposes and also providing important inputs to the risk management related research of NAAQS
implementation planning gave it high priority. For a more complete treatment of this subject see
the NARSTO-A documents on atmospheric sciences and source emissions research needs (White
Paper and Charter Plan).
39
-------
3.6.10 Overarching Concepts
3.6.10.1 Inclusive Approach
Particulate matter is a complex mixture of condensed phases, gases, and materials that
transfer from one phase to another (semivolatile components). Gas-phase pollutants may be
absorbed on or dissolved in particles. All of these components interact physically and
chemically and may affect the body in interactive ways. Therefore, nonvolatile, semivolatile,
and gaseous components may contribute collectively to health effects, and all three components
of air pollution should be included in controlled-exposure studies and in exposure measurements
for epidemiological studies.
3.6.10.2 Interdisciplinary Collaboration
The technical skills from a wide range of disciplines must be joined together to resolve the
uncertainties in the air pollution-health effects relationship. On-going workshops, symposia,
research conferences, etc., based on multidisciplinary approaches representing the relevant
disciplines, are needed. Centers of excellence that facilitate the development and work of multi-
and interdisciplinary teams provide one approach. Research training mechanisms with a focus
on cross-disciplinary perspectives and collaboration need to be developed.
The attendees at PM Research Needs Workshop supported the following planning research
need: "Expand the interdisciplinary discussion (involving epidemiology, toxicology/dosimetry,
and exposure) conducted at this workshop in order to better define and prioritize the research
needs especially to identify multidisciplinary approaches and programs to address the reserach
needs." Accordingly, EPA expects to participate in additional interdisciplinary workshops to
define specific research programs.
The CASAC panel emphasized the need for cross-disciplinary and international
interactions. The efforts of atmospheric scientists, laboratory researchers, clinical researchers,
and epidemiologists will be required to resolve several of the uncertainties, and consideration
should be given to providing a framework for integrating these efforts. CASAC also indicated
the need for research training with a focus on cross-disciplinary perspectives and collaborations.
40
-------
3.6.10.3 International Collaboration
The need for collaboration in international efforts by U.S. scientists and U.S.-supported
researchers also was noted by the CASAC panel. As an example, the panel recommended
collaboration of EPA and its supported researchers in international efforts such as the "Air
Pollution and Health: European Project."
Different countries use a variety of PM indicators. These differ in upper and lower cut
point, in conditioning and other processes that determine loss or retention of semivolatile PM,
and in what component or parameter of PM actually determines the measurement (e.g., British
smoke measures elemental carbon). EPA staff considers the international harmonization of PM
indicators to be a high-priority need.
3.7 TIMING OF RESEARCH TASKS
3.7.1 The 5-Year Cycle
The 5-year cycle for review of the standards for criteria air pollutants, as specified by the
Clean Air Act, defines the time at which research results can most effectively impact the standard
setting process. Major milestones for the next PM NAAQS review cycle, as published in the
Federal Register (Vol. 62, No. 205, page 55,202, October 23, 1997), are given in Table 3-4.
Projected key dates for research timing are as follows.
Preparation of the next Air Quality Criteria for Paniculate Matter will be initiated in
spring/summer of 1998. The first external review draft of the AQCD is to be released in
July/August 1999. A CASAC meeting to review the AQCD is to be held in October/November
1999. A second public review draft of the AQCD, revised according to CASAC and public
comment, will be issued in March 2000 for further public review and comment. A final
CASAC Meeting to review the second external review draft of the PM AQCD is to be held
in May/June 2000.' This CASAC meeting is expected to be the last feasible point to consider
The external review drafts will include research available in the published, peer-reviewed literature at the time
of their preparation. To facilitate inclusion of the latest research in the final PM AQCD, EPA expects, in
cooperation with other funding agencies and appropriate technical organizations, to co-sponsor a scientific meeting
or series of meetings (probably in early 2000) to provide a focus and incentive to complete and report research in
time to be included in the final PM AQCD. Arrangements will be made for expedited peer review and publication
of papers presented at the meeting.
41
-------
Table 3-4. Major Milestones in PM NAAQS Review
October 1997
Nov. 1997 -Jan. 1998
March 1998
April 1998 -Dec. 1998
Feb./March 1999
March 1999 -July 1999
July/August 1999
Aug. 1999 - Oct. 1999
Oct./Nov. 1999
Nov. 1999 - Feb. 2000
March 2000
March 2000 - May 2000
* May/June 2000
May 2000 - August 2000
September 2000
Sept. 2000 - Nov. 2000
Nov./Dec. 2000
Dec. 2000 -April 2001
May 2001 -July 2001
August 2001
Sept. 2001 -Nov. 2001
November 2001
Dec. 2001 -April 2002
May 2002 - June 2002
Julv 2002
PM NAAQS Review Plan to CASAC
Prepare PM AQCD Development Plan
CASAC Meeting on PM AQCD Development Plan
Prepare Workshop Drafts of PM AQCD Chapters
Peer Review Workshops
Prepare External Review Draft PM AQCD
Draft PM AQCD to CASAC
Public Comment Period on Draft PM AQCD
CASAC Meeting on Draft PM AQCD
Prepare Revised PM AQCD and Draft Staff Paper
Revised PM AQCD and Draft Staff Paper to CASAC
Public Comment Period on Revised PM AQCD and Draft Staff Paper
CASAC Meeting on Revised PM AQCD and Draft Staff Paper*
Prepare Revised Staff Paper and Final Revisions to PM AQCD
Revised Staff Paper to CASAC, Complete Final PM AQCD
Public Comment Period on Revised Staff Paper
CASAC meeting on Revised Staff Paper
Complete Final Staff Paper and Develop Proposal Package
OMB/Interagency Review of Proposal Package (90 days)
Publish Proposal in Federal Register
Public Comment Period on Proposal (90 days)
CASAC Meeting on Proposal
Review Public/CASAC Comments and Develop Promulgation Package
OMB/Interagency Review of Promulgation Package (60 days)
Final Promulgation Packase Sisned bv Administrator
* Projected last feasible point for CASAC discussion of newly published (or accepted for publication) peer-reviewed
research for incorporation into final PM AQCD.
newly published (or accepted for publication) peer-reviewed research for incorporation into the
final PM AQCD (which is to be completed by September 2000).
Having examined the crucial research issues and the timing set by the PM AQCD schedule,
it is clear that, to address the research needed to resolve the scientific uncertainties in the
PM-health relationship, four types of research tasks must be considered:
(1) tasks that could be funded in 1998 that might provide useful results for the next PM AQCD;
(2) research support tasks that should begin in 1998 to form the basis for longer term studies that
would impact the next PM AQCD (likely scheduled completion in 2005);
42
-------
(3) longer term tasks requiring 5 to 6 years to complete, but which should be initiated in 1998 or
1999 to provide results by 2005; and
(4) tasks requiring 3 years that could be initiated as late as 2000 or 2001 and still provide
research results for 2005.
3.7.2 Tasks To Produce Research Results in Time To Impact the Next
Particulate Matter AQCD
This section describes tasks that could be initiated with FY 1998 funds and that could
produce results of significant value in addressing PM-health uncertainties in the 2000 AQCD.
The tasks will be discussed in terms of the issues that they address.
3.7.2.1 Effects of Long-Term Exposure to Particulate Matter
Epidemiology
(1) There may be populations or cohorts that are being (or have been) studied for factors other
than air pollution, such as the American Cancer Society (ACS) cohort used by Pope and
co-workers, that could be analyzed in the next few years using existing air pollution
concentration data.
(2) There may be more information that can be obtained from existing long-term cohort studies
(such as the ACS and Harvard Six Cities studies). For example, the relationship of
ACS mortality data to PM2 5 and sulfate concentrations has been analyzed, but not with
respect to PM10, PM|0_2 5, or ozone concentrations (which also should be available).
Additional composition data may be available for the Harvard Six Cities (e.g., from X-ray
fluorescence analysis) that could be used to examine the relationship of various health
outcomes with transition element metal concentrations or possibly various source categories.
(3) Various factors that vary from city to city and that might either influence mortality or the
relationship between ambient concentration and average community exposure to ambient
pollution could be examined. By accounting for such factors, it might be possible to better
define the PM-mortality relationship.
(4) Ongoing studies to investigate the long-term effects of other pollutants could be expanded to
include PM.
43
-------
Toxicology/Dosimetry
Organizations that have existing facilities for controlled exposure of laboratory animals to
participate pollutants could investigate the effects of exposures lasting for several months.
Studies of this duration would provide information to supplement acute instillation studies and
might provide useful insight into the relationship between internal dose and effect and the
balance between damage and repair.
3.7.2.2 Susceptibility, Who and Why?
It may be possible to gain some insight into susceptible populations from completed,
ongoing, or new epidemiologic studies, or from studies with young or elderly laboratory animals
or with laboratory animal models of human disease.
3.7.2.3 Mechanisms of Biological Response
The types of studies described below could provide useful information on biological
mechanisms responsible for acute effects in time to impact the next PM AQCD.
• Toxicologic studies (with humans, laboratory animals, and cultured cells) to examine effects of
collected, dried, ambient particles; individual chemical components of fine and coarse PM; and
ultrafine and accumulation-mode particles of the same chemical composition.
• Toxicologic studies with young and old animals and with animal models of human disease.
• Expansion of existing toxicology programs using concentrated ambient particles. These
programs should be fully funded to allow the maximum number of experiments and adequate
scientific manpower to expedite data analysis to provide peer reviewed papers accepted for
publication by May or June 2000.
• Of particular interest are studies that show promise of elucidating how pollutants in the lung
might cause effects in other organs. Examples include cardiac, vascular, and hematologic
responses; immunological responses; neurological responses; and release of various
blood-borne mediators.
44
-------
3.7.2.4 Key Components
Toxicology/Dosimetry
Toxicologic studies could be conducted to examine the relative toxicity of different PM
components found in fine and coarse particles. The same chemical species may be present in
both fine and coarse PM, but may have different biological effects because it is present as
different compounds or in different matrices. It will be important when comparing potency of
different components to use particles of the same size so that differences caused by composition
may be examined separately from differences resulting from particle size. Toxicology studies
also could be done with collected, dried, ambient particles from different areas with different PM
sources and composition.
Epidemiology
At the time the current PM AQCD was finalized, there were few epidemiological studies
that actually had data on PM2 5 and PM(10_2 5). There are now, or will be by September 1998,
several additional databases available with concentration data on indicators of fine-mode
particles and the coarse fraction of PM10 particles, including several data sets with daily XRF
elemental composition. For example, such concentration data sets are being developed for
Philadelphia (1991 to 1994), Phoenix (1995 to 1997), and Pittsburgh (1995 to 1997). There may
be other concentration data sets available to individual investigators. Although most of these
databases do not have ideal concentration data, they are adequate to provide needed further
information on the association of mortality and other health outcomes with fine and coarse
particles and gaseous pollutants within the time available before the next AQCD.
It would be useful to have some information on the magnitude and variability of the errors
in the measurement of concentration resulting from the following four factors: (1) measurement
error in the mass of fine and coarse particles caused by intrusion of coarse-mode particles into
PM25 (and the corresponding loss of coarse-mode particles from PM(10_2 5), (2) errors in total
mass and mass of ammonium nitrate and semivolatile organic compounds because of loss of
such semivolatile species during sampling and equilibration of filter samples, and (3) error
introduced by using a concentration measurement at one point in a city to represent the
community average (i.e., failing to account for the spatial variation across a community).
45
-------
With regard to item 1 it would be useful to measure the size distribution of particles in a
variety of locations and seasons and to measure the size distribution under ambient conditions.
Because a number of continuous mass measurement techniques require dehumidification before
measuring PM mass, the particle size distribution also should be measured after dehumidifying
the air stream. With regard to item 2, it would be useful to have some experimental
measurements of the concentrations of semivolatile components for a variety of seasons and
locations. With regard to item 3, it would be useful to examine the evenness of the spatial
distribution of the coarse component of PM10 across a community and the mass and individual
components of fine PM.
Exposure. An important uncertainty in epidemiologic studies is the use of such
a community average concentration (based on one or several monitors) as a surrogate to
represent the average personal exposure to ambient pollution of individuals in the community.
At the 1997 Workshop, the exposure group recommended an exposure study and several special
studies that could advance the understanding of the relationships of ambient concentration to the
four components of personal exposure and provide near-term information to improve exposure
indices used in epidemiological studies.
For community monitoring networks, it will be necessary to determine if the PM mass (and
other PM parameters and components and gaseous pollutants) are distributed sufficiently evenly
throughout the community so that a sampler at one site (or the average of a small number of
sites) will yield an assessment of the community average concentration, suitable for use as a
basis for exposure indices for epidemiologic analysis on both a 24-h and a seasonal basis. Once
the spatial distribution has been determined, additional research studies will be required to
develop exposure models to relate ambient PM concentration to average community personal
exposure to ambient PM, the exposure parameter needed for epidemiologic analysis on a
community basis. People are exposed to pollutants outdoors (ambient). However, people spend
much of their time indoors, in homes, offices, commuting vehicles, or other microenvironments,
where they are exposed to ambient pollutants that have infiltrated into the microenvironments
(ambient-infiltrated) and to other pollutants that are generated within the various
microenvironments (indoor-generated). They are also exposed indoors and outdoors to
46
-------
pollutants due to their personal activities. The relationships among these four types of exposure
parameters, (1) ambient, (2) ambient-infiltrated, (3) indoor-generated, and (4) personal activity,
need to be studied. The ratio of the personal exposure to ambient pollutants to the ambient
pollutant concentration will depend on the nature of the pollutant, the amount of time the person
spends in various indoor environments, and the nature of the microenvironments, rate of indoor-
outdoor air exchange and rate of removal of pollutants that penetrate indoors. For acute studies,
the ratio of average community personal exposure to ambient PM to the ambient PM
concentration measured at a community monitoring site will vary with season and day of the
week. For chronic studies, it will vary with seasons, climate, and economic and cultural
differences among the different cities. Studies also are needed to characterize indoor-generated
pollutants and to determine if there is a correlation between community exposure to indoor-
generated pollutants and ambient pollutants that might cause indoor-generated pollution to be a
confounder in community epidemiology studies.
3.7.3 Research Support Tasks
Several tasks need to be initiated with FY 1998 funds to provide tools or information to
support longer term studies that will provide research results for the 2005 AQCD.
3.7.3.1 Effects of Long-Term Exposure—Epidemiology
There are existing and planned studies that follow the health status of groups of individuals
(cohorts) for various reasons other than to determine the health effects of air pollution. However,
data from these studies might be used to investigate the effects of air pollution. A survey should
be conducted to identify existing and planned cohorts that could be used to study the effects of
air pollution. Some cohorts may be used directly for chronic epidemiological studies, as has
been done with the American Cancer Society cohort. In other cases, minor changes may make
the cohorts useful for chronic air pollution epidemiology. This survey also should provide
information on the location of cohort members to help determine which communities should be
chosen for long-term monitoring.
In addition, development of biomarkers or health indicators (e.g., pulse oximetry,
fibrinogens level, etc. for cardio health endpoints) would enhance long-term epidcmiologic
47
-------
studies, as would development of improved modeling strategies to better address confounders,
copollutants etc.
3.7.3.2 New Tools for Toxicology
Particle Concentrators
The use of a high-flow virtual impactor to concentrate accumulation-mode particles for
animal studies has proven to be a very useful tool. The extension to concentration of
coarse-mode particles by using a larger cut point size is relatively easy. The extension of the
concentrator principle to nuclei mode or ultrafme particles has yet to be demonstrated. The
development and demonstration of such a device would provide a tool available for toxicologic
research that could be used to answer questions regarding the importance of ultrafme particles as
they exist in the atmosphere.
Particle Generators
The particle concentrators are very useful tools, but they depend on the ambient aerosol,
which varies in composition and concentration. It would be useful to have a generation system
that would provide particles of atmospheric size and composition in equilibrium with gas-phase
and semivolatile aerosol components. Such a system could be provided by the combination of
a combustion or high-temperature source to generate metal and carbon-nuclei-mode particles, a
smog chamber flow reactor in which the nuclei could age in the presence of photochemical
generation of PM and in equilibrium with source and photochemically generated gas phase
pollutants, and an accumulation-mode (or possibly also a nuclei-mode) concentrator to furnish
the desired concentration of particles that simulate in situ atmospheric particles, but that can be
controlled in terms of the composition of the gas and particle phase. The development and
demonstration of such a facility would provide a useful tool for controlled exposure studies.
Diagnostic Tools
More sensitive, but less invasive, techniques arc needed to identify and measure the effects
of inhaled air pollutants (gases and particles) on the lung and other organ systems. New,
innovative, and promising techniques should be considered for support.
48
-------
3.7.3.3 New Tools for Exposure Assessment
The current cut point of 2.5 um is the appropriate indicator for determination of compliance
with the present fine-particle standards. However, because a portion of the coarse mode is in the
1- to 2.5-um size range, a 2.5-um cut allows some coarse-mode particles to be included in the
sample. Perhaps even more importantly, some of the coarse-mode particles are not included in
the PM(10_2 5) sample. Particles in the 1- to 2.5-um region have a high deposition fraction in both
the tracheobronchial and alveolar regions. Attribution of these particles to the wrong size
fraction may lead to misinterpretation of data on epidemiologic associations of health outcomes
with fine and coarse particles. An idealized example of fine- and coarse-mode particles, showing
the particle size fractions collected by TSP, PM,0, PM2 5, and PM(!0_2 5), is shown in Figure 3-3.
70
60
05 50
~S)
=t
a 40
O)
=- 30
V)
20
10
Fine-Mode Particles
Coarse-Mode Particles
TSP
HiVol
0.1 0.2 0.5 1.0 2 5 10 20
Particle Diameter, |im
•< Total Suspended Particles (TSP) *
50 100
PM10 (<10 um) (Thoracic)
PM2 5 (<2.5 um)
0-2.5)
( (2.5to10nm)(
Figure 3-3. Idealized size distribution of ambient particulatc matter showing fine and
coarse modes, the portion collected by various samplers, and the overlap of
PM2 5 and the coarse fraction of PM,0.
49
-------
Another problem has to do with the loss or retention of semivolatile compounds such as
particle-bound water, ammonium nitrate, and certain organic compounds. PM collected on a
filter and dried provides a measurement of the mass of the nonvolatile components of suspended
particles plus a variable fraction of the semivolatile components. With current filter-conditioning
techniques, mass measurement can be reasonably precise when side-by-side samplers are
compared and the filters are processed identically. However, slight changes in the temperature of
the filter during sampling, the time and filter-temperature during handling and storage, and the
precise temperature and relative humidity during equilibration can lead to significant differences
in the amount of semivolatile PM lost. Therefore, samples collected at different sites in the same
network or in different networks may contain different amounts of semivolatile material leading
to uncertainties in comparison of mass results from different locations. An example of fine-
mode particles showing the semivolatile components and how changes in relative humidity can
affect the mass mean diameter of the fine mode by changing the amount of particle-bound water
is given in Figure 3-4.
One of the difficulties in preparation of the 1996 PM AQCD was the inadequacy of the
monitoring database. The monitoring database for the preparation of the 2000 AQCD also will
suffer from some inadequacies, although, hopefully, the inadequacies will be better understood
and there will be some information to quantify the uncertainties. However, to ensure that a better
monitoring database will be available for the 2005 AQCD, research monitoring networks should
be initiated by 2000 (with FY 1999 funding). Therefore, it is important that studies be performed
in 1999 (with FY 1998 funding) to field test new monitoring techniques and decide which ones
can be used in research and compliance monitoring networks. Particularly important are
techniques for collecting semivolatile components and measuring their mass and composition,
separately or as part of a total suspended PM mass measurement; improved separation of fine-
and coarse-mode PM (e.g., by dehumidification of the air stream prior to separation); measuring
particle number and size distribution; samplers that integrate over weeks to provide
cost-effective, long-term averages of mass and composition; and continuous methods for
PM mass and components to allow characterization of short-term peaks.
50
-------
Semivolatile
Components
Subject to Loss
Particle-Bound
Water
(NH4)XS04
X= 0 to 2
C elemental
Mineral/Metal
Figure 3-4. Major chemical components of PM2-s showing semivolatile components that
may be lost during sampling, handling, storage, or conditioning.
3.7.4 Long-Term Studies That Need To Be Initiated with FY 1998 Funding
3.7.4.1 Research Monitoring Networks
Extensive research monitoring networks will be required to provide ambient pollutant.
concentration data needed to support exposure assessment for future chronic and acute exposure
studies. The network should measure fine and coarse mass and a variety of other components
and parameters. For chronic studies, long-term measurements are needed in 40 to 60 cities for
10 years. The desired seasonal resolution may be obtained by integrating daily samples or by
using samples that integrate over 2 weeks to a month. For cost-effectiveness, this network
should consider the pattern successfully used by IMPROVE (Interagency Monitoring of
Protected Visual Environment) (i.e., samplers should be installed at local monitoring network
sites, samples should be collected by local agency personal, and samples should be sent to a
51
-------
central laboratory for analysis). There could be several central laboratories, each responsible for
one or more types of analyses.
For acute epidemiologic studies, to identify causal agents and develop dose response
information, a more extensive set of measurements would be needed but in fewer cities.
Measurements should include physical measurements (particle number, size distribution, etc.)
as well as measurement of fine and coarse mass and a variety of chemical components on
a 24-h basis and, if possible, continuously. This network should be run for 3 to 5 years in each
of 5 to 20 cities to provide an adequate database for acute epidemiology.
EPA's OAQPS is planning an extensive expansion of local monitoring programs to obtain
measurements of PM2 5 mass and composition. This network, to be supported through EPA's
state grant program, is intended primarily to provide air quality information to determine
compliance (i.e., is the standard being met?). However, it also may provide air quality
information (concentration measurements) useful for acute and chronic epidemiology, for study
of the relationships between ambient concentrations and indoor concentrations, and for
evaluation of models of emissions and air quality. This local monitoring program may provide
certain data needed by the research monitoring program. The ORD research monitoring should
be carefully integrated with the OAQPS local monitoring program. The research monitoring
program should cooperate with local agencies and focus on adding additional instruments and
measurements to local monitoring sites, intensive programs for short-term investigations, and
facilitating distribution and use of the monitoring data. Cooperative arrangements with
universities for enhancement of monitoring sites and use of monitoring data for research
purposes, including examination of the spatial distribution of PM concentrations, would
encourage prompt feedback on the usefulness and quality of monitoring data and any needed
changes in the network.
At the 1997 Workshop, the exposure group suggested that data from the near-term
exposure studies, they recommended could be used to design the most feasible monitoring
approach to support exposure assessment for future chronic and acute exposure studies. These
studies could also provide more information on the relationship between ambient central-site
concentrations and personal exposures to the hazardous components of PM.
52
-------
The next three sections discuss in some detail specific research needs in epidemiology
(Section 4), toxicity and dosimetry (Section 5), and exposure assessment (Section 6).
4. EPIDEMIOLOGY
4.1 BACKGROUND
The review of available epidemiologic findings in the Air Quality Criteria for Paniculate
Matter led to the following conclusions.
• The epidemiologic literature reveals consistent, statistically significant associations of
increased short-term ambient PM levels with increased frequency of mortality, morbidity,
respiratory symptoms, and short-term reduction in children's lung function. This literature also
shows statistically significant associations of elevated long-term PM levels with elevated
frequency of mortality resulting from respiratory and cardiovascular causes.
• The epidemiologic database relating to short-term ambient PM exposure exhibits considerable
internal consistency (similar observations in multiple studies conducted in different locations)
and coherence (association of ambient PM exposure with a variety of health effects across a
wide range of severity).
• To date, the effects of short-term ambient PM exposure are much better characterized than the
effects of long-term exposure.
• Available findings strongly suggest that effects of ambient PM exposure are especially severe
in elderly adults, especially those with underlying cardio-pulmonary illness. Because about
75% of all deaths occur in persons aged 65 and above, and because observed associations of
PM concentration with mortality are strongest in this group, the public health burden of
PM-attributable mortality is probably greatest in this group.
• Available findings also show associations of long- and short-term ambient PM exposure with
respiratory morbidity and symptoms in children.
• PM chemical composition and size distribution differ among areas. Currently, it is uncertain
whether PM exposure-response relationships observed in a given area are applicable to other
areas with different PM characteristics.
53
-------
1 The shapes of PM exposure-response relationships for various health and physiologic
endpoints and for different subgroups of the overall population have not yet been clearly
established.
1 In time-series studies of short-term ambient PM exposure, several statistical techniques have
been employed to adjust for potentially confounding effects of weather and season.
Associations of PM exposure with health effects have been generally robust across different
analytical methods, but effects of respiratory infectious illness outbreaks and other potentially
relevant covariates have not been fully explored. Also, the influences and interactions of
non-PM pollutants, such as ozone, CO, and nitrogen oxides, on PM exposure-response
relationships are not yet fully understood.
Uncertainty remains as to the specific physical and chemical PM constituents, and as to the
specific PM field measures, that have the closest mechanistic relationships with the
PM-associated health effects observed in epidemiologic studies. For example, available
evidence is not conclusive regarding the effects of thoracic PM (generally measured as PM10 or
PM15) relative to the fine and coarse fractions of thoracic PM, or of fine PM relative to coarse
PM. At the same time, current evidence suggests stronger relationships of adverse effects with
fine PM and its constituents than with coarse PM and its constituents.
Confounding by non-PM air pollutants may occur and non-PM pollutants may contribute to
adverse health effects either independently of, or in conjunction with, PM. However, the
consistency of estimated PM effects, in the presence of varying concentrations of other air
pollutants, strongly suggests that observed PM-associated health effects are indeed largely
attributable to PM.
Many available epidemiologic findings on PM are subject to uncertainty arising from PM
measurement error and potential misclassification of PM exposure. Measurement technologies
for different PM constituents remain subject to different degrees of imprecision. Thus,
statistical health effects estimates for different PM constituents potentially are subject to
different levels of uncertainty and may be biased to different extents. The magnitudes of these
uncertainties, and of the biases that they may introduce into epidemiologic findings, have not
yet been determined.
54
-------
It will be very important to design future epidemiologic studies of PM to maximize the
inherent strengths of the epidemiologic method and to minimize its limitations. Increased
understanding of relevant biological mechanisms will come primarily from experimental studies
(see Section 5). However, with thoughtful study planning and conduct, future epidemiologic
studies can reduce most of the uncertainties identified at the beginning of this document. For
example, such studies will be essential in quantifying effects of ambient PM on severe health
outcomes such as mortality and hospitalization. They also will be very useful in quantifying
community health effects of different physical and chemical PM constituents, and in
characterizing the role of PM in relation to potentially confounding factors such as non-PM air
pollutants and weather parameters. In some locations, it also may be possible to assess health
effects of specific PM sources or source categories.
Future epidemiologic studies should be conducted in locations with different mixes of PM
constituents. Because fine- and coarse-mode PM fractions differ with respect to sources'and
composition, these fractions often may exert different effects on the respiratory and
cardiovascular system and on other body systems. Therefore, in future studies, it will be
important separately to measure and assess fine and coarse mode fractions of thoracic PM.
It also will be important to assess a variety of health-related outcomes.
Further community-based studies also can make significant contributions in exposure
assessment (see Section 6). For example, such studies are needed to characterize the contribution
of indoor-generated particles to total personal exposure and to clarify relationships between
ambient concentrations and personal exposure to ambient PM for different indoor-outdoor
activity patterns. Improved understanding in these areas will enable more accurate modeling of
personal PM exposures from community-wide exposure data.
Studies of PM health effects at realistic U.S. ambient levels should generally be given
priority. However, clear epidemiologic tests of effects of different PM constituents are often
difficult to achieve in the United States. International studies can provide the opportunity to
investigate health effects across wider ambient PM exposure gradients, and with greater variation
in PM constituents, than commonly occur in the United States. Judicious site selection can also
provide exposure gradients with lower ends that overlap the U.S. ambient PM range. Thus,
international studies can be of value to elucidate further the shapes of PM exposure-response
55
-------
relationships by deriving such relationships across a wider range of PM exposure than occurs in
the United States, to assist in determining the generalizability of exposure-response curves
among different locations and ethnic groups, to gain understanding of the extent to which
U.S. environmental regulations benefit public health, to assist in fulfillment of international
obligations of the U.S. government, and to provide scientific data of direct utility in host
countries' risk assessment and risk management activities.
Epidemiologic research needs for ambient PM are presented in the next Section 4.2. Brief
discussion and justification precedes each specific need or set of closely related needs. Needs are
discussed and listed in rough order of scientific priority or temporal sequence.
4.2 PM EPIDEMIOLOGY RESEARCH NEEDS
4.2.1 Interdisciplinary Planning
It will be very important to precede new epidemiologic studies with a thorough planning
effort that involves epidemiologists, biostatisticians, experimental scientists, and funding
organizations. In this, consideration should be given to investigating the effects of different
physical PM attributes (e.g., ultrafme, fine, and coarse fractions and PM number); investigating
the effects of different chemical PM constituents (e.g. transition metals, acid, sulfates, organic
compounds, and biological components); investigating independent, additive or synergistic
effects of gas-phase pollutants, including gases in or on PM; and investigating associations of
health outcomes with specific PM source categories. It will be necessary to plan studies that
investigate effects of long-term and short-term ambient PM exposure on a variety of
health-related outcomes. It will probably be necessary to conduct new epidemiologic studies
in multiple locations.
In the planning process, it will be important to choose incisive, feasible study designs.
Studies should be located in areas that provide adequate exposure contrasts. That is, in a given
location (or set of locations), characteristics of variability in long- or short-term ambient
PM levels should provide clear tests of effects of pollutants of interest on health outcomes of
interest. Design-related issues will be complex because PM contains many different chemical
and physical components, local levels of some PM components tend to be intercorrelated over
56
-------
time, temporal and spatial variation in ambient PM levels generally are limited in the
United States, and the financial resources and time available for further PM studies are likely to
be limited. The planning effort should weigh the relative merits of studies which require
recruitment of new cohorts and those which employ cohorts already established (e.g., the
Harvard Six-Cities Study, the Lung Health Study, or the Inner City Asthma Study).
Research Need 4.1—Initiate and sustain a comprehensive interdisciplinary planning
effort for future epidemiologic studies of ambient PM. This effort should foster close
communication among scientists, between scientists and funding organizations, and among
funding organizations.
4.2.2 Incidence of Premature Mortality and Time of Life Lost
Epidemiologic studies show associations of both short-term and long-term PM exposure
with mortality, especially in elderly persons with underlying cardio-pulmonary illness. Some
evidence also suggests that long-term PM exposure may be also associated with lung cancer
mortality. The existing PM-mortality database is subject to uncertainties which should be
addressed and resolved in future epidemiologic studies. For example, geographic differences in
effects estimates have been observed among studies of short-term PM exposure and mortality.
These differences may reflect geographic differences in ambient PM toxicity, population PM
exposure, or underlying population characteristics. They also may reflect statistical artifacts to
some extent. Additionally, mortality effect estimates from available studies of long-term PM
exposure appear to be considerably higher than those from studies of short-term exposure. The
correct interpretation of this apparent difference is not yet clear.
The extent to which PM-mediated mortality occurs in advance of life expectancy is not
known. Available information suggests that in different decedents, shortening of life could
conceivably range from days to years. Further understanding of PM-mediated life shortening
will be valuable in quantifying the public health burden of ambient PM exposure. Future
research should address life shortening in relation to both short- and long-term PM exposure.
This research may well entail the difficult task of constructing estimates of life expectancy in the
presence of all prevailing risk factors except ambient PM exposure.
57
-------
Future epidemiologic studies of PM and mortality should be closely coordinated with
experimental studies, which are actively exploring biological mechanisms through which
ambient PM could plausibly produce or promote mortality in humans. In future epidemiologic
studies, individual decedents should be characterized whenever possible with respect to time and
place of death, smoking habits, medical history (including recent history of respiratory infection),
life style, and other relevant covariates.
Research Need 4.2—Determine the incidence of premature mortality attributable to
short- and long-term ambient PM exposure.
Research Need 4.3—Determine time of life lost to PM-mcdiated mortality and the
shape of dose-response relationships for mortality effects.
4.2.3 Public Health Burden of Particulate Matter Exposure
The public health burden of long-term PM exposure remains poorly understood, but could
be substantial. Further characterization of the extent to which long-term PM exposure produces
incremental, chronic damage to the cardio-pulmonary system and other systems is therefore
needed. It is also necessary to determine the extent to which long-term PM exposure interacts
with other risk factors, such as smoking, to induce or exacerbate cardio-pulmonary disease.
Further understanding of long-term PM exposure effects will also be valuable in assessing the
biological coherence and plausibility of epidemiologic observations to date. Both nonmalignant
disorders and cancer should be assessed as feasible. Assessment of the extent to which ambient
PM exposure early in life predisposes to chronic illness later in life would also be valuable, if
feasible.
In assessing respiratory effects of long-term exposure, one approach could be to investigate
the growth or decay of lung function in relation to ambient PM exposure, and the relationship
of lung function changes with other PM-associated outcomes such as mortality and cardio-
pulmonary morbidity. Sensitive early biological indicators of chronic, permanent disease
(biomarkers of effect) also are needed. Hypothesis generation for future epidemiologic studies
of long-term PM effects should draw on relevant mechanistic findings from experimental studies.
Locations in which large changes in ambient PM levels or PM composition will occur, or
have occurred, could provide highly desirable settings for future epidemiologic studies of long-
58
-------
term PM exposure effects. In these locations, health and physiologic outcomes could be
measured (or quantitatively estimated) both before and after the change in exposure occurs. Such
changes in exposure (environmental interventions) can occur in locations where large industrial
PM sources have closed or opened, fuel for electric power generation has changed, or
environmental regulations have effected, or will effect, substantial reduction in the level of
regulated pollutants. If feasible, studies in the latter type of location would be especially
desirable because they could provide assessment of the effects of regulation on both ambient
exposure and public health.
Research Need 4.4—Characterize health effects of long-term ambient PM exposure.
Research Need 4.5—Determine relative public health burdens of long-term and short-
term ambient PM exposures.
Research Need 4.6—Assess feasibility of longitudinal studies in locations where
environmental regulations have effected, or are expected to effect, substantial reduction in
ambient PM levels.
4.2.4 Relative Health Effects of Key Attributes of Particulate Matter
Much further study is required to characterize the relative importance of different physical
attributes and chemical constituents of PM in producing or promoting adverse health effects.
Thoughtful study designs, thorough measurement of PM constituents, and systematic assessment
of possible interactions among PM constituents, should be employed. This research need also
includes further characterization, in long-term exposure studies, of the relative health effects of
PM exposures occurring at different times during, or before, the study period. Such
characterization will require accurate, thorough construction of long-term PM exposure histories
for study subjects and populations. Close communication with toxicologists will be highly
desirable, to ensure that key PM constituents identified in experimental studies are included in
exposure assessment.
Research Need 4.7—Further characterize the relative health effects of specific
physical and chemical constituents of ambient PM.
59
-------
4.2.5 Interactions of Particulate Matter and Gaseous Pollutants
Further study is also needed to characterize the health effects of PM alone and in
combination with other ambient air pollutants, and to determine the relative public health
importance of PM and non-PM pollutants. Study designs providing clear exposure contrasts of
PM and non-PM pollutants will be required to advance understanding on this point. These
pollutants also should be measured thoroughly in selected study locations. Assessment of
interactions between PM and non-PM pollutants will also be important in addressing this
research need. Advances in biostatistical theory, and application of state-of-the-art statistical
methodologies to epidemiologic research, will be highly desirable.
Research Need 4.8—Further characterize the health effects of ambient PM in
combination with other ambient air pollutants (e.g., O3, NO2, CO, SO2).
4.2.6 Role of Weather and Climate
Weather factors often (but not always) have turned out to be important in evaluating the
health effects of short-term exposure to PM and other criteria air pollutants. Weather is causally
related to air pollutant concentration (dispersion) and, to a lesser extent, to pollutant emission
rates. Health effects of weather factors are therefore often confounded with health effects of air
pollution. Adverse health effects of weather are particularly associated with some of the same
respirator}' and cardiovascular symptoms that are also associated with air pollution exposure.
It would be especially helpful to separate direct effects of weather on health from indirect effects
of weather that predispose or mediate health effects of air pollution. It will thus be important to
characterize further the roles of meteorological factors, as potential confounders and/or as
interacting stressors, in contributing to observed associaticas of PM exposure with health
outcomes.
Research Need 4.9—Determine the role of weather and climate as potential
confounders and/or interacting stressors in both short-term and long-term PM health
studies.
60
-------
4.2.7 Susceptibility, Who and Why?
Further identification of PM-susceptible populations, and determination of PM effects in
these populations, are needed. Of special importance in this regard will be further
characterization of PM health effects in elderly adults, especially those with cardio-pulmonary
illness, and in children. In the elderly, epidemiologic and experimental studies should
concentrate on the combined cardiovascular and respiratory effects of PM exposure. In children,
ambient PM effects on acute respiratory illness and symptoms, and on asthma, should be further
assessed. More thorough evaluation and understanding of host factors that place particular
classes of individuals at greater risk for experiencing ambient PM-induced health effects are also
needed, including evaluation of socio-demographic (e.g., gender, SES, occupation, smoking
status, diet) and biologic (e.g., genetically-predisposing factors, co-morbidity factors, etc.).
Further understanding of such host determinants of PM susceptibility is required in all age
groups.
Research Need 4.10—Further characterize PM-susceptible subpopulations and
determine ambient PM effects in these subpopulations.
Research Need 4.11—Identify and characterize predisposing risk (biologic and
socio-dcmographic) factors in relation to PM-attributable health effects.
Research Need 4.12—Determine combinations of host factors, both biologic and socio-
demographic, that may interact with each other and/or other stressors (e.g., non-PM
pollutants, meterologic factors, etc.) to increase PM-rclatcd health risks.
4.2.8 Effects of Short-Term Exposure
Previous epidemiologic studies have consistently shown associations of short-term PM
levels with highly adverse outcomes such as mortality and hospitalization in adults. Further
epidemiologic studies are needed to quantify the effects of short-term exposure on these and
other outcomes, and to determine the extent to which these effects vary across locations with
different ambient PM characteristics, different ambient pollution mixtures, and different suites of
nonpollution risk factors.
Panel studies of adults with cardio-pulmonary illness have previously contributed to
understanding of health effects of short-term exposure to ambient PM and other air pollutants.
61
-------
Such studies should be resumed. These could possibly enroll outpatient adults with moderate-to-
severe disease and serially measure cardio-pulmonary pathophysiologic events that could signal
adverse clinical outcomes, such as hospitalization or mortality. Measured events might include
electrocardiographic changes, alterations in spirometric lung function or peak flow, and indices
of pulmonary inflammation and systemic hypoxia.
It also will be important to characterize further the extent to which short-term PM exposure
exacerbates asthma. Possibly, further panel studies of asthmatics could be conducted, in which
the effects of different physical and chemical properties of ambient PM and of PM in
combination with other pollutants would be determined and compared.
Research Need 4.13—Further confirm and characterize health effects of short-term
ambient PM exposure.
4.2.9 Markers of Acute and Chronic Health Effects
Future studies of PM health effects will benefit by the enhanced use of physiologic,
immunologic, and molecular markers of adverse health effects. Effort should be devoted to
identification, validation, and application of new, incisive markers. The sensitivity and
specificity of putative markers should first be determined against the appropriate health
outcomes. Markers shown to be sufficiently sensitive and specific could then be applied in
epidemiologic studies. This effort is especially important in view of limited financial resources
for PM research, and the consequent need for application of economical, time-compressed study
designs to the maximum extent consistent with scientific soundness. Also, increased use of such
markers will maximize the contribution of epidemiology to understanding of biological
mechanisms of PM action. Markers of both acute and chronic disorders should be considered,
as should markers of disorders of the respiratory, cardiovascular, and other body systems.
Sensitive, but minimally-invasive, techniques for measuring markers are also needed.
Research Need 4.14—Identify, validate, and apply markers of adverse acute and
chronic health effects in epidemiologic studies.
62
-------
4.2.10 Exposure-Response Relationship
The shapes, and spatial and temporal generalizabilities, of PM exposure-response
relationships have not been fully characterized. It is recognized that epidemiologic studies
provide only limited ability to characterize such relationships. At the same time, epidemiology-
based exposure-response relationships are likely to play an important role in future regulatory
risk assessments, as in past assessments. Thus, efforts to characterize and refine exposure-
response relationships are needed. Relevant specific issues include shapes of relationships for
different PM constituents, health outcomes, and subpopulations; linearity or nonlinearity of
response; presence and location of thresholds and inflection points within the PM exposure
range; and shapes of exposure-response relationships above "background" PM levels.
Research Need 4.15—As feasible, further characterize and refine exposure-response
relationships for ambient PM in the community setting.
4.2.11 Statistical Analyses of Uncertainty
Further research is needed to characterize the extent to which the findings of epidemiologic
PM studies are subject to uncertainty arising from measurement error, and to bias arising from
misclassification of PM exposures. Results of this research will provide important guidance in
designing, analyzing, and interpreting future epidemiologic studies. In this effort, it will be
desirable to explore further "classical" error and variance structures (dealing with individual
means) and "Berkson" error and variance structures (dealing with population means), and to
identify their appropriate applications in PM-related epidemiology. It will also be desirable to
characterize specific conditions under which exposure misclassification would, and would not,
bias results toward or away from the null.
The statistical implications of measurement-related error and bias should be characterized
and compared for individual PM size fractions and chemical constituents. In addressing these
issues, error and variability arising from the following sources should be assessed as feasible and
appropriate: measurement error due to inaccurate capture of PM by monitors or lack of precision
of collocated monitors, PM size- or composition-dependent differences in geographic
homogeneity of ambient concentration, PM size- or composition-dependent differences in
particle penetration from outdoors to indoors, differences in indoor rcsuspcnsion and airborne
63
-------
lifetime of ambient PM constituents, contribution of indoor-generated particles to total particle
exposure, and differences among individual subjects' indoor-outdoor activity patterns and
ventilation rates.
The variety of potential errors in PM exposure indices and the wide range of indicators
used to measure PM (TSP, PM10, PM2.5), the presence of covariates (various numbers of
meteorological variables, ambient levels of various copollutants), and, in some cases, how
variables were defined or aggregated (e.g., current day PM, 3-day average or lagged PM), make
it very difficult to compare or combine results from different studies. This is in contrast to
biomedical and pharmaceutical research, which have similar needs for research synthesis, but for
which proven statistical methods (viz., meta-analysis) are widely available. Clinical studies or
trials are typically "controlled", viz., experiments designed to investigate differences between
treatment and control groups with known precision and power. Synthesis is typically performed
on studies investigating the same endpoint (e.g., mortality), using meta-analytic methods to
produce combined estimates of overall significance (viz., a combined p-value) or standardized
differences in endpoints between treatments and controls (viz., a combined effect size).
Unfortunately, experimental controls for defining baseline conditions are usually not available in
environmental research, because they are difficult to define, identify, and enforce. A significant
gap in assessment science is the lack of a quantitative methodology for performing combined
analysis and producing combined estimates of exposure, effects and exposure-effects
relationships, and of uncertainties associated with these estimates. Synthesis of environmental
research studies requires an expanded meta-analytic paradigm, or entirely new paradigms and
methods. An important first step towards development of quantitative methods for
environmental research synthesis and an important contribution to understanding the
environmental effects of particulate matter would be the development of statistical methods for
combining PM-epidemiology studies.
Research Need 4.16—Further characterize measurement error and exposure
misclassification of both PM and co-pollutants, and assess their statistical implications in
cpidemiologic studies of ambient PM.
Research Need 4.17—New statistical techniques need to be developed to permit
comparison of PM cpidemiologic studies with a variety of different types of uncertainties.
64
-------
4.2.12 Biomedical Assessment of Origins, Stages, and Progression of
PM-Associated Disorders in Humans
Finally, further studies are needed to advance basic understanding of the epidemiology,
pathogenesis, and progression of PM-associated disorders, irrespective of environmental effects
on these disorders. Though such studies will often be sponsored and conducted by organizations
other than EPA, their results will be useful in forming and testing hypotheses in environmentally
targeted studies. For example, gaps in understanding of the epidemiology of mortality impede
formation and testing of hypotheses as to air pollution effects on mortality. The pathogenetic
mechanisms and natural history of asthma have not been fully elucidated. The extent to which
subclinical cardiac changes predict overt cardiac disorders, including arrhythmias, is not well
known. Improved understanding of these and other topics will improve the ability to identify the
points at which exposure to PM and other pollutants might maximally influence the frequency or
severity of disease. Such understanding will also assist in selecting incisive health-related
endpoints in environmentally targeted epidemiologic studies.
Research Need 4.18—Further characterize the epidemiology, pathogenesis, and
progression of PM-associated disorders.
5. TOXICOLOGY AND DOSIMETRY
5.1 BACKGROUND
Human and animal toxicology and dosimetry studies are important in characterizing the
exposure-dose-response relationship for PM. Dosimetry is defined as characterizing the
determining factors along the entire exposure-dose-response continuum. Thus, it involves
consideration of not only what fraction of ambient PM is inhaled and deposited, but also how the
deposited material is cleared (e.g., dissolution or mucociliary transport) and what the target cells
and effector relationships are that control damage and its repair. Susceptibility is viewed as
resulting from differences in the amount of deposition in the lungs (dose) for the same exposure
or as being caused by differences in response (sensitivity), or both. Understanding these factors
will contribute to more accurately characterizing acute and chronic health effect. Such
investigations include controlled exposures of humans and laboratory animals to PM and its
65
-------
various constituents, in vitro studies of the mechanisms of particle-cell interactions, and physical
and mathematical modeling of PM deposition, distribution, clearance, and retention. Such
studies are essential to determine mechanisms of action for the toxic components of PM on the
respiratory, cardiovascular, and other systems.
The size distribution of ambient aerosols is a critical factor influencing the extent to which
particles penetrate into the respiratory tract, how and where the particles deposit, and how and at
what rate the particles are cleared from the respiratory tract. The relative contribution of each
deposition mechanism (interception, impaction, sedimentation, diffusion, and electrostatic
precipitation) varies for each region of the respiratory tract (extrathoracic, tracheobronchial, and
alveolar). Subsequent clearance of the deposited particles depends on the initial deposition site,
physicochemical properties of the particles (e.g., solubility, propensity for aggregation, etc.),
translocation mechanisms such as mucociliary transport and endocytosis by macrophages or
epithelial cells, and on time since initial deposition. Retained particle burdens and ultimate
particle disposition are determined by the dynamic relationship between deposition and clearance
mechanisms.
This discussion separates research needs into investigation of factors influencing dose and
factors modifying response.
A major objective of human and laboratory animal studies is to understand the biological
mechanisms that underlie the epidemiologic observations. To achieve this objective, dosimetry
studies that identify the ambient PM components that cause certain effects (e.g.,
cardiopulmonary events), better define potential target cells and tissues, and identify attributes of
potentially susceptible populations (e.g., individuals with preexisting disease or other
compromising factors) will ultimately aid development of the data needed to better assess
individual lung dose and its variability.
Particle size, composition, and solubility factors influence the disposition of particles in the
cardiopulmonary system and target and effector cellular relationships. To understand the
metabolic changes of cells, as well as cell-particle interactions and the relationship of particles to
cells, specific anatomic sites must be examined. The population of cells making up specific
regions must also be considered given their differing functions and ability to respond to different
stimuli presented in the form of particles. Therefore, the cellular composition of various regions
66
-------
of the pulmonary and cardiovascular system must be understood to better define differences in
response to particle exposure.
Ambient PM can be broadly divided into coarse and fine modes based on size, formation
mechanisms, composition, and atmospheric removal processes. Fine particles can be further
classified as nuclei and accumulation mode particles. Fine-mode particles are typically formed
by combustion processes or atmospheric reactions involving SO2, NOX, and organic compounds.
In contrast, coarse mode particles are typically formed by mechanical abrasion, evaporation or
suspension processes and include soil dust and associated minerals. Although differences in size,
per se, may be associated with differences in toxicity, differences in composition between coarse
and fine modes due to differences in sources may also influence their inherent toxicity. The
components or characteristics of ambient PM that contribute to the adverse responses (morbidity
and mortality) observed in epidemiology studies must be identified. Understanding which
components, or interactions between components, are key to the toxicity of PM is basic to
designing health-protective and cost-effective control strategies.
In occupational settings and in controlled experiments with healthy humans and laboratory
animals, exposures at mass concentrations much higher than ambient rarely, if ever, lead to
sudden death. It is suspected that some unique factors regarding either the toxic properties of the
ambient aerosol or the susceptibility of the people who experience health effects related to PM
may be responsible. Studies with ambient particles, concentrated ambient particles that retain the
characteristics of ambient particles, or simulated ambient particles generated in smog chambers
are needed to determine if ambient particles are indeed more toxic than laboratory-generated
particles. Studies using laboratory animal models of human disease and using humans with lung
disease will be required to address the second factor. Studies that evaluate responses to PM in
young as well as in old animals are also needed to investigate susceptibility related to age.
Further characterization of the individuals in the population who are dying from PM exposure is
needed to aid in the design of controlled exposure studies.
67
-------
5.2 DETERMINANTS OF INHALED PARTICLE DOSE
Respiratory tract geometry, and its interaction with airflow and particle aerodynamics, is a
major determinant of inhaled particle dose. Available models of inhaled particle deposition rely
on limited experimental data obtained in small numbers of subjects (humans or laboratory
animals). This limited database does not permit characterization of the variability in inhaled
dose resulting from differences in respiratory tract geometry (e.g., differences in structure and
airflow related to species, sex, age, health status) or caused by different physicochemical
characteristics of aerosols (particle size, density, distribution, hygroscopicity). Data on basic
anatomic (dimensions) and physiologic (ventilation) parameters are required to construct
dosimetry models for populations with various attributes. Data on inhaled particle deposition for
different aerosols are required to validate these models. It will be necessary to develop better
data on the inhalability of particles in laboratory animals. Although PM]0 particles are largely
inhalable by humans, such is not the case for many laboratory animals, especially small rodents.
There are definite gaps in the database for deposition of particles in laboratory animals that
currently hamper the development of inhalability curves. Adjustments for inhalability are a
critical step in any dosimetric extrapolation of biologically effective dose. Recent work suggests
that increased deposition may occur in children in part because of their greater relative
ventilation. Another consideration is that people perform different levels of activity at different
times, which result in different ventilation patterns. For example, whether humans breathe
through their nose only or oronasally (mouth and nose) can have an important impact on
inhalability and deposition pattern. Factors that control or influence the oronasal breathing
transition are not well understood. These ventilation-time-activity patterns could be linked with
exposure data for microenvironments to construct a 24-h personal inhalation exposure and
thereby enhance the predictive capability of dosimetry models.
Research Need 5.1—Characterization of anatomic dimensions (e.g., length, diameter)
and data on differences in inhaled particle deposition (mass and distribution) as a function
of species, age (children, adults, elderly), sex, and health status (e.g., preexisting
cardiovascular or pulmonary disease).
Research Need 5.2—Characterization of inhaled particle deposition for monodispcrse
particles with different physicochemical characteristics, including particle aerodynamic
68
-------
diameter, and hygroscopicity. In addition, effects of particle density, size, distribution,
shape, and charge on deposition patterns require further evaluation.
Research Need 5.3—Improved characterization of human-ventilation activity
patterns for various cohorts (e.g., sex, age, and health status, recreational and occupational
activities) and improved data on factors affecting the oronasal breathing transition.
Research Need 5.4—Improved models that account for the deposition of particles of
different sizes and compositions as a function of species, age, sex, and health status.
A much better understanding of particle deposition in people with lung disease especially is
needed, including relationships between deposition, clearance, and degree of functional
impairment.
Research Need 5.5—Examine the relationship between particle deposition pattern
and location of airway injury or inflammation.
5.3 DETERMINANTS OF TOXICANT-TARGET INTERACTIONS AND
TISSUE RESPONSE
5.3.1 Clearance and Repair
"Dose" should be expressed in terms of particle mass, number, and/or surface area. Dose
should also be normalized in terms of tissue burden (e.g., per unit of regional respiratory tract
surface area, per number of ventilator/ units, per number of alveolar macrophages). In addition,
the time over which the dose is accumulated should be considered (e.g., dose rate, cumulative
dose, etc.). For specific mechanisms that are implicated in PM health effects, data should be
collected to aid in the construction of appropriate dose-response models (e.g., measure tissue
response to potentially causative constituents such as transition metals). In contrast to acute
effects, chronic effects may depend on the retained dose rather than the dose initially deposited.
Clearance involves both absorptive (i.e., dissolution) and nonabsorptive (i.e., transport of intact
particles) processes. Data to help characterize these processes (e.g., macrophage/epithelial cell
endocytosis rates and mucociliary translocation ) for particles of different sizes and
physicochemical properties (e.g., solubility, propensity to aggregate) are required. A major
research need concerns retention patterns for inhaled particles. Retention takes into account the
69
-------
net impact of deposition and clearance, and, as such, is a critical factor that must be related to
health outcomes. Most often, retention data are obtained by assessing deposition and clearance
processes. In characterizing exposure-dose-response relationships among species, lack of
knowledge about the retained dose at the target site is often the weak link when attempting to
extrapolate laboratory animal toxicological results to humans. Characterization of both acute and
chronic effects requires data on repair mechanisms and rates. Chronic effects could be due to
cycles of repeated acute damage and repair as well as chronic particle retention. Further basic
research on the relationship between acute damage and repair cycles and the development of
chronic lung disease are required to understand mechanisms of chronic effects from inhaled
materials.
Research Need 5.6—The following are required across species, age (children, adults,
elderly), sex, health status (e.g., preexisting cardiovascular or pulmonary disease), and
presence of smoking habit for different particle sizes and compositions:
• improved understanding of physicochemical properties that influence clearance and
retention (e.g., dissolution-absorption characteristics and propensity to aggregate or
disaggregate in respiratory tract fluid or cells);
• data on rates of clearance and other translocation processes (e.g., macrophage/cpithelial
cell endocytosis rates; mucociliary transport);
• data on rates of repair for different tissues and cells damaged by PM; and
• further development and testing of dosimetry (deposition and retention) models that
account for clearance and repair processes.
5.3.2 Host Susceptibility
Several components of ambient PM have been implicated as contributing to its toxicity
(e.g., transition metal content and solubility, acidity, organic acids, and biogenic materials).
A persisting issue however, is the disparity between exposure levels eliciting PM effects in
controlled toxicology studies and the remarkably lower ambient exposure levels associated with
increased mortality in epidemiologic studies. Healthy laboratory animals used in toxicology
studies may not be suitable models of humans susceptible to PM. Laboratory animal models of
human disease, reflective of humans responding adversely to ambient PM, must be further
70
-------
developed and validated. A better understanding of the physiological characteristics of
susceptible human subpopulations will be required. It is important to determine whether
components of ambient PM that are only weakly active or inactive in healthy laboratory animals
elicit significant effects in compromised laboratory animal models.
The working population, while not necessarily the most susceptible population, represents a
large group for exposure, presensitization, long-term acclimation and dosage to a wide variety of
substances. For example, farm workers in a dusty environment with exposure to airborne
fumigants, insecticides, and herbicides may be a geographically and ethnically diverse group that
could be appropriate for study of chronic PM effects. Chronic studies involving healthy
laboratory animals exposed to concentrated ambient particles provide an opportunity to
determine if PM is involved in the development of chronic pulmonary disease. Such studies may
provide a link to community epidemiologic studies suggesting that long term PM exposure is
associated with increased mortality.
Enhanced susceptibility may result from greater deposition and/or retention caused by
differences in lung physiology related to age (young or old) or result from disease and damage to
a part of the lung, (e.g., emphysema) or be caused by greater sensitivity to damage from
preexisting inflammation or damage from disease. Chronic PM exposure may result in repeated
lung injury that could lead to chronic respiratory changes, especially in individuals sensitized to
PM or its constituents. Therefore, characterizing the nature and pathogenesis of respiratory tract
injury caused by chronic inhalation of appropriate PM components would be extremely
important. It will be necessary to identify those factors affecting susceptibility, identify their
influence on dose-response functions, and determine the distribution of such factors in the
population.
Research Need 5.7—Determine, in the course of cpidcmiological and controlled
human exposures studies, the potential physiologic and pathophysiologic characteristics
(including age and health status) of the human population that may put certain individuals
at increased risk from inhaled PM.
Research Need 5.8—Further develop laboratory animal models of human disease
(including cardiovascular disease, per se, as well as cardiovascular disease with pulmonary
involvement, chronic obstructive pulmonary disease, allergy, and pulmonary hypertension)
71
-------
and determine the extent to which they mimic human disease characteristics in order to
evaluate the role of these diseases in exacerbating the response to inhaled PM. The effects
of nonuniform pulmonary ventilation and ainvay hyperreactivity on the responses to PM
also need to be investigated.
Research Need 5.9—In laboratory animal studies, exposure protocols should be used
that will facilitate the comparative evaluation of the potential toxicity by inhalation of
different components of PM, singly and in combination. Concentrated ambient PM used in
controlled exposure studies should include, in addition to collected and redispersed PM,
concentrated dispersed ambient particles that remain in equilibrium with gases present in
the ambient air. Techniques are needed for concentrating ambient particles in the
accumulation mode and in the nuclei mode (ultrafine particles). Both PM and gases should
be characterized. Laboratory animal models that best simulate sensitive human
subpopulations should be used.
Research Need 5.10—Transformation of healthy laboratory animals to susceptible
laboratory animals as a consequence of chronic PM exposure needs to be examined.
Because of the paucity of information regarding toxic constituents of PM, a well
characterized urban PM would be appropriate mixture would be appropriate for a chronic
PM exposure study because it would likely contain many of the toxic components.
Cytotoxicity, inflammation, oxidant stress, and altered lung cell function all have been
reported as aspects of the respiratory tract response to relatively high concentrations of ambient
PM components. Defining the critical in vivo targets (e.g., epithelial cells, macrophages, upper
or lower airways) and the nature of effects (e.g., oxidant production, cytokine release) is
important for developing more sensitive approaches and identifying biomarkers to assess the
adverse effects of PM in epidemiology, toxicology, and especially human clinical studies. The
responses to specific PM constituents or ambient PM mixes may differ considerably among
different types of lung cells. Although most studies of ambient PM toxicity have focused on
respiratory tract responses, increased attention should be given to characterizing responses
outside the lung (e.g., cardiovascular system, immune system, central nervous system, etc.).
These may represent important secondary targets of PM exposure, particularly in sensitive
individuals.
72
-------
Because PM morbidity and mortality are primarily associated with individuals with
pulmonary or cardiopulmonary disease, it would be most relevant to study the effects of PM in
such individuals. However, serious ethical constraints limit the extent to which severely
compromised subjects can be involved in controlled exposure studies. It is likely that only
individuals with mild to moderate forms of chronic obstructive pulmonary diseases (COPD),
heart disease, asthma, or respiratory infectious disease can be studied. More sensitive
biomarkers or physiological indicators would be especially useful for such studies.
Morbidity and mortality associated with particle exposure may be due to suppression of
pulmonary host defenses, or alterations in inflammatory responses resulting in exacerbation of
these diseases. Humans with infectious or allergic disease may be particularly sensitive to
particles. Alternatively, predisposing disease may enhance the toxicity of the particle, for
example, by delaying clearance.
Laboratory animal models exist for viral and bacterial respiratory infections and allergies.
Viral strains exist that have been used in some controlled human exposure studies. The effects of
particles on production of immune mediators by alveolar macrophages and epithelial cells,
in vitro, could be examined in combination with viruses or viral antigen. In addition, the
exacerbation of inflammation by microbial or antigenic substances may play a major role in the
response to subsequent inhalation of PM.
Research Need 5.11—Identify the most sensitive target sites including specific
macromolecules, cells, organs and systems affected by inhaled PM. The potential effects of
PM mixtures should be evaluated by coordinated inhalation studies with laboratory
animals and humans. In addition, in vitro tests (e.g., human lung cell cultures) also may be
useful to explore specific mechanisms. Immediate or secondary responses of tissues outside
the lung (especially cardiovascular and immune systems) should be studied. Specifically,
how might PM deposition in the lung lead to cardiac toxicity or secondary cardiac effects in
individuals with cardiac disease?
Research Need 5.12—Determine whether mild asthmatics, COPD patients with mild
bronchitis or emphysema, and patients with allergic and infectious diseases are more
responsive to PM than healthy adults. Effects of particle size as well as specific chemical
components will need to be studied separately. Possible markers of effects might include
73
-------
airway inflammatory responses, changes in specific and nonspecific airway reactivity,
increased retention of inhaled particles, impaired clearance of inhaled particles, and
changes in lung function (airway resistance, spirometry, diffusion). Additional studies are
required in laboratory animal models of infectious or allergic disease. It will be important
to distinguish mechanisms that are nonspecific such as irritation, mechanical disruption of
epithelium and increased permeability from mechanisms that activate specific immune
responses.
Toxicology and epidemiology would benefit greatly by identification, validation, and
application of markers of PM-mediated health effects. Markers of environmental PM exposure
also may prove useful. Such markers must be validated experimentally before they are applied in
epidemiologic studies. The sensitivity and specificity of candidate effects markers should be
determined against the appropriate health and physiologic outcomes. The sensitivity and
specificity of candidate exposure markers should be determined against actual environmental
levels of appropriate PM constituents. In these efforts, priority should be given to development
of markers that can be collected noninvasively.
Specific candidate PM effects markers include putative indices of cardiac pathophysiology,
immunologic activity (including pulmonary inflammation/edema), hypoxia, airways obstruction,
genotoxicity, and possibly cancer. Specific candidate PM exposure markers include levels of
some transition metals and organic compounds, or their metabolites, in respiratory secretions,
blood, urine, or stool, and counts and size distributions of ambient particles present in carefully
collected sputum samples.
The ultimate utility of chemical substances as markers of ambient PM exposure or effect
will depend largely on the degree to which the PM-specific contribution to body levels of those
substances (or their metabolites) can be detected against endogenous body stores of the same
substances. Thus, for example, it appears unlikely that useful markers of ambient iron, sulfate, or
acid exposure could be developed, because endogenous stores of these substances are already
high.
Research Need 5.13—Identify and validate physiologic, immunologic, and organic
chemical markers of adverse PM-mediatcd health effects and markers of environmental
PM exposure.
74
-------
5.3.3 Host Adaptation to PM-Induced Health Effects
Repeated exposures to air pollutants may result in an attenuation of certain health effects
associated with air pollutant exposure. This has been shown to occur for ozone where repeated
exposures to ozone has resulted in the attenuation of acute physiological and certain
inflammatory effects induced by this air pollutant. The mechanisms responsible for this host
adaptive response to ozone exposure are currently unknown. Adaptation to the adverse health
effects associated with air pollutant exposure may reflect a dynamic host response originating
from genetic, physiological, cellular and molecular processes. Adaptation could involve a
strengthening of defense mechanisms and so protect the organism. Adaptation could also result
ultimately in an exhausting of defense mechanisms leaving the organism more susceptible to
injury. Currently, it is not known whether host adaptive responses occur following repeated
exposure to ambient air particulate matter (PM). The ability of the host to adapt to PM exposure
may have an impact on the health effects associated with chronic PM exposure as well as PM
host susceptibility. Therefore, it is important for PM research to include studies to examine the
issue of host adaptation to PM-induced health effects by addressing the following research needs:
Research Need 5.14—Determine which biological and physiological responses may
undergo adaptation following repeated PM exposures and whether these PM-induced
adaptive responses have an impact on the health effects associated with chronic exposure to
PM;
Research Need 5.15—Determine dose-response relationships and cellular
mechanism(s) for PM-induced host adaptive responses;
Research Need 5.16—Examine the effects which pre-existing disease has on the ability
to adapt to the health effects associated with PM exposure;
Research Need 5.17—Determine whether other co-pollutants can influence the ability
to adapt to the health effects associated with PM exposure.
75
-------
5.4 PHYSICAL CHARACTERISTICS OF PARTICLES
Epidemiologic evidence suggests that fine-mode PM may be responsible for a substantial
portion of PM-health effects. The comparison of effects of fine versus coarse mode PM is
limited, but because of their different deposition patterns in the respiratory tract (as well as
differences in sources, composition, and number), effects are likely to vary between one segment
of the respiratory tract and another. Particle size (i.e., ultrafine, fine, coarse) is an important
factor in access to target cells within the lungs and to other organs via systemic routes. Particles
have a variety of target tissues that could potentially influence the outcome of exposure.
Deposition on epithelial surfaces, translocation to the interstitium and pulmonary capillaries,
movement to the lymph nodes and processing by immune effector cells (dendritic cells [antigen
presenting cells]) all could have different endpoints and corresponding responses.
It might be asked whether the most important issue is particle size, per se, or is particle
composition, especially surface chemistry, equally or more important than size. Studies should
focus on simple particles that can have their surface modified; more complex particles from
which components can be "stripped"; and well characterized particles collected from specific
urban or rural sites, preferably in conjunction with concurrent epidemiologic studies. A program
of in vitro particle toxicity testing might be appropriate for preliminary evaluation of the
differential toxicity of PM from different sites.
The contribution of ultrafine particles to ambient PM toxicity is unknown. Limited studies
have been performed using ultrafine PM in humans (diameter < 0.10 um). In toxicologic studies
conducted thus far, the ultrafine particles in addition to existing as singlet particles also form
agglomerates of 0.1 /j.m or larger. It is important to identify the factors that favor disaggregation
of these agglomerates in the lung. The mechanism of action of poorly soluble ultrafine aggregate
particles is unclear at present. Ultrafine particles are more rapidly transferred to the interstitium
than fine (0.3 //m) size particles of the same composition, and ultrafines exhibit a greater
accumulation in the regional lymph nodes and an increased retention time in the lung. Moreover,
studies on cell activation and inflammatory mediator release indicate that ultrafine aggregate
particles of low solubility are markedly more effective, in vivo, than larger particles of the same
composition in activating macrophages to release potent proinflammatory cytokines, resulting in
lung inflammation.
76
-------
Research Need 5.18—Evaluate responses to exposures of coarse, fine, and ultrafine
particles. Such studies are needed in humans and in laboratory animal models, as are
in vitro studies using isolated cell systems. Different durations of exposure (acute,
subchronic, and chronic) also should be evaluated.
Research Need 5.19—More information is required on human exposure to ultrafine
PM and on the response of pulmonary cells to ultrafine particles. Only limited data are
available for clearance and retention of ultrafine particles in humans; particularly useful
would be the role of chemical composition and solubility.
5.5 POTENTIAL CAUSATIVE AGENTS
5.5.1 Ambient Aerosol
Ambient particles are in equilibrium with a variety of gas-phase substances that can be
adsorbed on the particle surface or dissolved in the particle-bound water of hygroscopic particles.
Highly water-soluble and reactive gases will be largely removed in the nose and throat.
However, if dissolved in particle-bound water, they may be carried deep into the lung, depending
upon the particle size.
Research Need 5.20—Experimental laboratory studies of the health effects of
concentrated ambient aerosol in equilibrium with existing gas-phase pollutants are
required (in situ aerosol). The results of these studies should be compared with those of
studies using collected (and stored) particles that are subsequently redispersed for
exposure.
Research Need 5.21—The potential effects of pollutant mixtures should be evaluated
in susceptible humans and laboratory animal models of disease. Especially important
would be mixtures of actual ambient PM with other commonly co-occurring air pollutants,
specifically those identified as potential confoundcrs in epidemiology studies (e.g., O3, SO2,
CO, NO2). These studies should focus on cndpoints other than mechanical effects on the
lung (e.g., cardiac electrophysiologic effects, inflammation, hypoxia, host resistance).
77
-------
5.5.2 Transition Metals
Transition metals can promote the production of reactive oxygen species (ROS), free
radicals such as the hydroxyl radical (OH) or the hydroperoxy radical (HO2), in the presence of
endogenous hydrogen peroxide and an appropriate endogenous reducing agent. The potential
importance of the transition metals in PM-associated oxidative stress and toxicity has been
established in studies of fibrous (e.g., asbestos) and nonfibrous (e.g., crystalline silica) mineral
particles. Transition metals present in the ambient atmosphere and in human lung autopsy
specimens include iron and to a lesser extent vanadium, nickel, manganese, zinc, and copper.
Intratracheal instillation studies using residual oil fly ash and urban PM have demonstrated an
association between soluble transition metal content and the ability to elicit pulmonary
inflammation and airway hyperreactivity in rats.
Results from intratracheal instillation studies have demonstrated that PM-associated soluble
transition metals, in addition to generating ROS, also induce acute pulmonary inflammation and
alter airway reactivity. These effects could contribute to adverse responses in susceptible
individuals. Recent findings indicate a role for transition metals in cardiac electrophysiologic
effects. Concentration-response inhalation exposures using laboratory animal models of human
disease will be useful to establish minimally effective exposure levels and will help characterize
the role of transition metals in urban aerosols.
Research Need 5.22—There is highly suggestive evidence from intratracheal
instillation studies that PM containing transition metals and atmospheric PM constituents
that can complex transition metals may be implicated in mortality and morbidity effects of
PM. Specific identification of the mechanistic role of transition metals in pulmonary
interstitial and airway responses and cardiac responses needs to be further evaluated.
Factors that influence PM solubility, oxidation state, and bioavailability should be
explored. These efforts should be guided by the outcome of analyses of the soluble
transition metal content of ambient PM.
5.5.3 PM-Associated Acid
Acidic aerosols may consist of aqueous acid droplets or acid coating on less soluble
particles. Studies in laboratory animals have typically not demonstrated significant acid-induced
78
-------
alterations in pulmonary function at near-ambient exposure concentrations. However, subtle
changes in lung morphology (e.g., mucous cell hyperplasia) and host defenses (i.e., altered
mucociliary clearance, macrophage function) have been detected after acute or subchronic
exposure to sulfuric acid concentrations of 125 to 300 Mg/m3.
Recent studies indicate that acid particle size and acid coating of particles influence the
activity of acid-associated aerosols. Greater and more persistent reductions in the intracellular
pH (an important regulator of cell function) of lung macrophages have been demonstrated in
guinea pigs exposed to ultrafine (-0.04 /^m) versus fine (0.3 ^m) acidic particles. Although the
mechanisms underlying the greater effect of ultrafine acid particles on macrophage pH remain
uncertain, studies suggest the importance of both the number of acid (or acid coated) particles
interacting with cells and the total acid dose to a cell. Coating of metal oxide particles with
sulfuric acid results in decrements in lung function (i.e., total lung volume, vital capacity, carbon
monoxide diffusing capacity) and increases in airway hyperreactivity at acid concentrations of
20 to 30 /^g/m3; similar effects are not detected when the metal oxide or pure acid droplets are
given alone. To the extent possible, the effects of acid-coated aerosols should be examined in
controlled human exposures.
Lower exposure concentrations and use of carrier particles characteristic of ambient PM
would increase the relevance of studies of acid-particle interactions. It is also possible that
acid-coated particles may interact with other components of ambient air pollution to result in
enhanced toxicity. For example, exposure of guinea pigs to ozone plus acid-coated ultrafine
particles was reported to result in greater impairment of lung function than exposure to uncoated
particles and ozone, or to a similar dose of aqueous acid droplets and ozone.
Previous studies have demonstrated that an acid pH can promote mobilization of iron or
other transition metals from particles and increase iron-dependent oxidant generation. The
demonstrated ability of acid and acid-coated particles to decrease the internal pH of lung cells
suggests a testable hypothesis of how acid exposure could increase the toxicity of particle
associated metals (i.e., by enhancing dissolution or bioavailability of metal constituents of PM).
Because chemical reactions between materials on the surface of particles may be important to the
effects of PM components, a better understanding of these reactions, especially as they relate to
79,
-------
the formation of more toxic materials, as well as the interactions between particle surfaces and
host factors (cells, proteins, lipids) is needed.
A considerable body of research on effects of aqueous acid aerosols (as opposed to
acid-coated PM) in human subjects has revealed a limited number of physiological effects. High
concentrations of acid aerosol slowed mucociliary clearance in healthy subjects (and possibly
also in asthmatics), with the effects being attributed to hydrogen ions. There are limited effects
of acid aerosols on lung function in asthmatics, a subgroup who appear to be somewhat more
responsive, at low, near ambient, concentrations. Laboratory-generated acid aerosols do not
appear to cause inflammation or changes in airway reactivity. Aqueous aerosol size (within the
PMjQ range) thus far has not been identified to be a factor in human exposures.
Research Need 5.23—The potential effects of PM-associated acid should be further
evaluated once the various forms in which acidic particles exist in the ambient environment
are more completely characterized.
Research Need 5.24—Mechanistic studies to characterize what factors (size, titratable
acidity, sulfate content) enhance the bioavailability and toxicity of acidic PM constituents
to the respiratory tract and other tissues.
Research Need 5.25—Controlled human exposures to acid-coated particles. Effects of
exposure to such particles have not been examined in humans. Methods for generating
such particles suitable for human exposure and in sufficient volume for controlled human
exposure may need to be developed.
5.5.4 PM-Associated Organic Compounds
It has been demonstrated that many organic compounds extracted from ambient PM are
genotoxic. Compared to organic extracts of ambient or combustion source PM, less information
is available on the genotoxicity of intact PM particles. Combustion-derived particles as well as
particles without a significant organic fraction have been shown to cause lung tumors in rats but
only at extremely high concentrations relative to ambient PM levels. To date, a clear and
consistent association has not been made between ambient air pollution exposure and human
lung cancer risk, although a relationship between environmental tobacco smoke and human lung
cancer risk has been shown.
80
-------
Studies do suggest that some organic components in ambient PM may contribute to acute
toxicity through a direct inflammatory action or the ability to complex or interact with other
components of ambient PM, such as metals. Organic compounds may influence the activity of
PM by forming complexes with metals. Humic-like substances (HLS) are organic acids present
in terrestrial and aquatic environments which because of their acidic functional groups can
complex metal cations. It is possible that by forming complexes with transition metals in a
manner that allows cycling between two stable valence states, HLS may contribute to the
oxidant-generating activity of ambient PM. Significant amounts of HLS are found in
combustion products of coal, diesel, oil, and wood and in PM collected on PM10 filters.
A significant correlation was observed between the amount of HLS in PM and metal content,
suggesting that the two may be associated.
Organic compounds also may induce inflammatory and immune responses. Both diesel
exhaust particles and organic extracts of diesel exhaust particles may enhance allergic antibody
(IgE) expression in vitro.
Research Need 5.26—In-vivo and in-vitro screening methods are needed to evaluate
the toxicity of PM-associatcd organic substances, which should be confirmed by laboratory
animal inhalation studies.
5.5.5 Bioaerosols
Bioaerosols consist of biological entities such as bacteria, viruses, fungal spores, pollens,
and plant and insect fragments, as well as compounds derived from diverse sources in the
ambient environment. These materials, which include endotoxins, proteins, condensed tannins,
proteases, glucans, and mycotoxins, can have potent effects on human health. Many bioaerosols
have a seasonal cycle, however, because of resuspension they may be present in the air
throughout the year. Endotoxins, a constituent of Gram-negative bacteria, are ubiquitous in
bioaerosols. Potential sources of bacterial endotoxin in the ambient air include tilled fields,
waste water treatment plants, grain dusts, cotton dusts, and wood dusts. Endotoxin primarily
activates macrophages, releasing a cascade of chemotactic factors, and brings about an invasion
of neutrophils into the respiratory tract. Treating ambient PM to inactivate endotoxin blocks its
in vitro macrophage activating effects. In vitro exposure of alveolar macrophages to diesel soot
81
-------
that did not contain endotoxin did not activate cytokine production. Endotoxins, a potent
inflammatory agent in the respiratory tract at levels of 10 to 50 ng/m3, have been implicated in
adverse human pulmonary responses to a variety of organic dusts in an occupational setting.
Although ambient levels of endotoxin are typically well below the nanograms per cubic meter
range, it is possible that sensitive individuals may respond to these low concentrations.
Condensed tannins are widely distributed in the stems and leaves of woody plants and are a
major component of the organic dust generated during commercial wood processing. Inhalation
of tannin-containing dust results in an acute pulmonary inflammatory response characterized by
the influx of neutrophils into the airways. Inhalation exposure to proteases, enzymes that
hydrolyze proteins and peptides, that usually are derived from industrial processes (e.g.,
detergent manufacture), can result in pulmonary irritation, inflammation, and, possibly,
emphysema. The induction of such effects is concentration-dependent and likely to be related to
the capacity to degrade proteins and to promote inflammatory processes. Glucans, constituents
of the cell walls of plants and microorganisms, are produced by many fungi (e.g., Actinomyces
and Streptomyces) and may facilitate the action of endotoxin and infective agents. Glucans may
exert their effects via specific glucan receptors or through the release of various cytokines.
Mycotoxins are metabolic products of fungi that can have important health effects in animals and
humans (e.g., on pulmonary macrophage phagocytic capacity). Mycotoxins have been shown to
be present in bioaerosols associated with grain and wood dusts.
Research Need 5.27—Measure the concentration of bioaerosols in ambient air and
their associations with PM-related morbidity and mortality (e.g., What is the
organic/inorganic ratio of ambient PM?). The potential health effects of biological
materials found in ambient air should be evaluated, alone, and in combination with various
other nonbiological PM constituents, in controlled inhalation exposure studies of
laboratory animals and humans.
5.6 METHODOLOGICAL ISSUES
There are a number of methodological issues which pertain to many of the toxicology
research needs.
82
-------
Instillation and Inhalation. Instillation studies are useful for generation of hypotheses
regarding biological mechanisms, active agents, and indicators (markers) of biological damage.
However, it is essential to include inhalation studies for dose-response assessments that can
provide information suitable for risk assessment. Further work is needed to understand the
implications of findings in instillation studies, where precise dose and deposition site information
can be obtained, with comparable inhalation studies, which mimic the realistic ambient
exposures. Intratracheal instillation studies often lead to inflammatory responses that may be
important confounders. The deposition of PM by instillation is typically less well dispersed than
in inhalation studies although localized dose can be well characterized. Difficulties in meeting
the needs of inhalation studies include finding enough material that is environmentally relevant,
the diversity of the materials that are present in the environment, generation of ambient particles
under controlled experimental conditions, resuspension of particles collected from the
environment, and resuspended particles may lose their original properties.
Animal Models. Further work is needed to explore the development of animal models that
more closely reflect the aged human with chronic cardiopulmonary disease and the extent to
which exposure contributes to cardiovascular and pulmonary damage. Animal models are
necessary for a number of toxicological and dosimetric studies of PM health effects. Further
basic research will be necessary to determine the extent to which these animal models of human
disease actually mimic the disease as it occurs in humans. Examples of such models which
require evaluation include monocrotyline-induced pulmonary hypertension as a model of
cor pulmonale, cardiomyopathy hamster as a model for congestive heart disease, elastase-
induced emphysema, sulfur dioxide-induced emphysema, various models of host resistance, and
aged animal models. To demonstrate sudden death risk to human populations with heart disease
but without chronic obstructive pulmonary disease (COPD), additional studies will be necessary
to determine the potential for an impact of PM exposure on cardiac function in animal models of
ischemic heart disease.
Controlled Laboratory Animal and Human Exposures. Exposure-dose-response
studies to ambient PM will require extensive chemical and biological, as well as physical,
characterization of the exposure atmosphere. For example, to what extent are the toxic properties
of the "live aerosol" retained when a virtual impactor-type particle concentrator is used? Can
83
-------
similar toxicologic effects be obtained when collected ambient particles are resuspended under
controlled exposure conditions. If collected particles are resuspended for controlled exposure
studies, how long does the aerosol need to be "aged" and under what conditions is the
resuspension most relevant to the ambient exposure. Comparisons of different types of particle
concentrators (e.g., virtual impactor, centrifugal) should be made.
Smog Chamber Generation of Simulated Ambient Aerosol. By operating a smog
chamber in a flow reactor mode, it is possible to generate an atmosphere of constant and
specified pollution at a flow rate adequate for animal or human exposure for periods of over a
week. The type and amount of gaseous and particulate pollution can be varied and controlled.
Sulfate particles can be generated in the presence or absence of nitrate particles. Organic
particulate may be present or absent. Ozone, sulfur dioxide, nitrogen oxides, and carbon
monoxide may be present at specified concentrations or removed. Primary particles of various
composition may be introduced from combustion processes or other sources. Particles formed
will be in equilibrium with gas-phase pollutants and will be present in size distributions
comparable to those found in the atmosphere. The operation of the generation system can be
varied to give different ratios of accumulation and nuclei-mode (ultrafine) particles. This
technique has been developed at EPA and used for mutagenicity testing and for the study of
pollutant damage to materials. For animal and human exposure studies, particle-concentrators
may be used to obtain the desired concentration level.
6. MEASUREMENT, CHARACTERIZATION, AND EXPOSURE
6.1 PARTICULATE MATTER RESEARCH PROGRAM WORKSHOP
During the PM Research Program Workshop held in November 1997, the exposure
break-out group (EG) discussed the research needs given in the exposure section (Section 6) of
the November 1,1997, draft of this document and began the process of converting research needs
into tasks and programs to address those needs. The EG felt that some of the needs in Section 6
were not true exposure needs but were related to other aspects of PM research. In response to
their concerns, the title of this section has been changed to indicate that it covers exposure
84
-------
research and other related research areas. The proceeding of the PM Health Research Program
Workshop are available as EPA/600/R-98/007.
This section has been reorganized with the first four sub-sections addressing the four key
questions identified by the EG. In response to the EG discussion, some new needs have also
been added and other needs statements have been modified.
6.1.1 Definitions and Conceptual Framework
Prior to setting and prioritizing research needs, the Exposure Group (EG) felt that it was
important to define exposure, to define PM and the PM components of interest, to place exposure
into a conceptual framework for addressing the overall research needs for PM, and to emphasize
the importance of sensitive populations.
6.1.1.1 Exposure
Exposure was defined as the concentration and time of contact between PM/gases and the
individual. In the case of PM, the point of contact was defined as the breathing zone.
Referencing exposure to the individual was considered essential, since it is the individual who
experiences the adverse health effects associated with elevated PM concentrations in air.
6.1.1.2 PM/Gases
PM/gases were defined as particles, criteria pollutants, and other gases in the air. Thus
exposure research related to PM/gases should address both particles and any gases that could be
confounders for adverse health effects. Particles were considered to include all possible
subclasses of particles. The EG also agreed with the discussion in Section 3.5.6 (i.e., personal
exposure to particles should be considered as the sum of exposure to ambient particles outdoors,
ambient particles that have penetrated indoors, indoor-generated particles, and particles
associated with personal activities).
6.1.1.3 Framework
Exposure research for PM/gases may be placed in the same framework as has been defined
for risk assessment and risk management within EPA. This workshop was directed toward
85
-------
exposure, dose (toxicology), and response (toxicology, epidemiology). Exposure research should
provide information on the concentrations, time frame, and components of PM exposure. These
data can then be linked to research in toxicology and epidemiology to develop risk assessments.
In turn, exposure data should also provide inputs for source and fate research including the
atmospheric measurement and modeling activities that will be conducted, by NARSTO. The EG
felt that this must be an iterative process with research in each area drawing on results from the
other areas, as well as providing important information to those areas.
6.1.1.4 Sensitive Populations
As a final point, the EG felt that it was important for PM exposure research to focus on
sensitive populations. These populations may have different activity patterns that could result in
substantially different exposures to PM/gases than the rest of the population. In addition,
sensitive populations include those individuals who will be adversely affected by exposure to
PM/gases.
6.1.2 Research Questions
In order to provide additional structure to the process of developing and addressing
research priorities, the EG framed four key exposure questions. Short- or long-term research
objectives were discussed for each question.
(1) What is the relationship of stationary monitors to ambient outdoor/ambient indoor/
indoor/personal exposure to PM/gases focusing on susceptible subpopulations? This
was considered a short-term research objective. As shown below, a study could be designed
to address this question and to provide critical information for developing hypothesis and
study designs for answering long-term questions?
(2) What are the physical/chemical characteristics of ambient/indoor/outdoor/personal
exposures to PM/gases? This was considered a critical question, especially as it relates to
identifying those PM/gas components of health importance. This should include iterative
86
-------
research with toxicology and epidemiology. Work to address this question should be started
in the short-term but it is expected to continue into the long-term.
(3) What is the population distribution of exposure to PM/gases of health importance as
iterated with toxicology and epidemiology having a focus on susceptible
subpopulations? This is the central exposure question with the highest priority. It is a
long-term research question. Hypotheses and study designs to address this question must be
developed with knowledge gained from the testing conducted as part of questions 1 and 2.
(4) What methodological improvements are needed to enable measurements of personal
exposure to PM/gases? Development/refinement of methods for PM/gases should be used
to reduce the uncertainty of measured exposure to PM , subclasses of PM and associated
gases. Method development should be prioritized to address those measurements that have
the greatest uncertainty. This was considered both a short- and long-term research question.
6.2 PERSONAL EXPOSURE: CONCENTRATION/EXPOSURE
RELATIONSHIPS
Key Question: What are the relationships between ambient concentrations of PM and
pollutant gases measured at stationary community (outdoor) monitors and (1) concentrations of
ambient PM/gases indoors and (2) personal exposure to PM/gases of ambient origin, focusing on
susceptible populations?
Studies are needed to characterize the extent to which ambient particles infiltrate into
various indoor microenvironments including homes, cars, office buildings, etc. Information
collected must be adequate to differentiate between indoor-generated particles and
outdoor-generated (ambient) particles. Ambient particles that infiltrate indoors may change:
acid particles may be neutralized by indoor ammonia, hygroscopic particles may change size if
the relative humidity changes, and semivolatile particles may evaporate if the vapor components
are readily adsorbed on indoor surfaces. Parameters must be identified and measured that will
permit separate estimation of personal exposure to ambient particles and to indoor-generated
87
-------
particles. These values may be modeled using measurements of ambient concentrations,
microenvironment concentrations, and estimates of the time spent outdoors and in various
microenvironments.
To the extent that susceptible populations can be identified, their exposure to ambient
particles (and perhaps to indoor-generated and personal activity particles) warrants emphasis.
However, it is not known exactly what factors cause people to be susceptible. It is also not clear
at -what stage in life exposure to particles may cause damage that will eventually show up as an
observable health effect. Therefore, an over emphasis on population groups currently thought to
be susceptible may be too limited.
Research Need 6.1—Ambient/indoor/personal exposure studies are needed that
differentiate ambient pollutants, including ambient pollutants that have penetrated
indoors, from indoor-generated pollutants and pollutants due to personal activities;
measure penetration and removal parameters; and develop quantitative indoor/outdoor
relationships that can be used to estimate personal exposure to ambient pollutants. Such
studies are needed for coarse-, fine-, and nuclei-mode particles; for components such as strong
acidity and nitrates; for SVOC's; and for gaseous pollutants such as ozone, carbon monoxide,
nitrogen dioxide, and sulfur dioxide.
Research Need 6.2—Personal exposure studies should be conducted that follow
selected subjects for extended time periods. Such serial studies will be more useful in
establishing correlations between ambient concentrations and personal exposure on a community
basis than studies of many people for one or a few days. Most useful, however, will be serial
studies that partition personal exposure to ambient pollutants from personal exposure to indoor-
generated pollutants and include both gaseous and paniculate pollutants.
Research Need 6.3—More comprehensive personal exposure studies are needed to
provide information across subpopulations, environments, seasons, and geographic areas.
Personal exposure assessment studies (that differentiate between ambient and indoor-generated
particles and between fine-mode and coarse-mode particles) are needed for different
subpopulations (healthy versus susceptible, smokers versus nonsmokers, young versus elderly,
work-at-home versus work outside the home, etc.); in a variety of environments (urban,
suburban, and rural); during different seasons and weather conditions (winter, spring, summer,
88
-------
and fall; humid and dry); and in different parts of the country (varying use of heating and air
conditioning and varying particle characteristics).
Research Need 6.4—Studies similar to those discussed in Research Need 6.1 are
needed to provide information on exposure to nitrates, semivolatile organic compounds,
and other PM components such as PMj and ultrafine particles that are not measured by
the Federal Reference Methods for PM2.s or PM10.
6.3 CHARACTERIZATION
Key Question: What are the physical and chemical characteristics of particulate matter and
pollutant gases found in ambient and indoor air and as experienced in personal exposures?
6.3.1 Measurement/Monitoring Programs
Research Need 6.5—The measurement techniques, developed in response to the needs
described in 6.5, need to be applied to characterize the composition and distribution of PM
for ambient air, indoor air, and personal exposure.
6.3.2 Size Distribution
A major problem in determining the best size cut for separating fine- particles from
coarse-mode particles is the apparent lack of agreement between size distributions measured by
impactors and those measured by in situ techniques that count individual particles such as light
scattering (optical diameter), time of flight (aerodynamic diameter), or electrical mobility
(mobility diameter). This lack of agreement may be caused by particle-bounce in the impactor
resulting in displacement of particles to smaller sizes. It also may be caused by size changes
resulting from small shifts in relative humidity as particles undergo heating or cooling during
sampling either in impactors or single-particle counters. Size-distribution data can also be
analyzed to provide more information on the correlation of particle number with volume and of
ultrafine or nuclei-mode mass with fine-mode mass.
Research Need 6.6—Measurements of size distribution, using co-located impactors
and particle count instruments of modern design, need to be conducted for several weeks in
89
-------
the summer and the winter in a variety of air pollution situations. Both types of size
distribution techniques should be equipped with devices that permit both increasing and
reducing the relative humidity.
6.3.3 Ultrafine Particles
To the extent possible, measurements of size distribution or measurements of total particle
number (condensation nuclei counts) should be added to the temporal and spatial variability
studies and the ambient/indoor/personal exposure studies discussed previously.
Research Need 6.7—Measurements of ultrafine or nuclei mode particles should be
conducted to determine their spatial and temporal variability; their correlation with
PM-fine; their penetration indoors; and their coagulation, growth, transformation, and
removal in indoor environments.
6.3.4 Indoor PM
Although indoor sources of PM are not of direct importance to the PM NAAQS, the
contribution of indoor air particles to total PM exposure needs to be understood to better
quantitate ambient PM exposure. The size distribution and composition of particles resuspended
by cleaning, walking, and other indoor activities need to be measured. Significant amounts of
indoor-generated particles are thought to come from biological sources including mold spores,
insect debris, etc. The size, sources, concentration, and potential health effects of such
indoor-generated particles, whether resuspended outdoor coarse particles that have infiltrated and
deposited indoors, suspended soil particles tracked into the house, or biotic or abiotic particles
generated within the home, need to be determined. The indoor sources of fine particles, other
than smoking, also need to be characterized. Research Need 6.8—Studies are needed to
improve characterization of the indoor sources of PM and the composition of indoor-
generated PM.
6.3.5 Reactions of Dissolved Substances in Particles
Chemical transformations occurring in ambient particles also may have implications for
mechanisms producing observed health effects. For instance, several recent studies have
90
-------
documented the potential toxicity of dissolved transition metals. Their solubility is determined
by their oxidation state, which in turn may be determined by photochemical reactions. The
photochemical oxidation of a large number of organic compounds (e.g., PAHs) also can produce
a wide variety of oxygenated products whose toxicologic properties are unknown. In addition, a
number of recent studies have suggested that chemical reactions occurring in or on atmospheric
particles (e.g., involving sulfates, nitrates, marine aerosols, yellow dust from the Gobi desert) can
exert substantial effects on the oxidizing capacity of the atmosphere. Current understanding of
such reactions is limited. Laboratory and field studies, along with integrative model studies, are
required to assess the importance of these reactions, in particular those involving organic
compounds, transition elements, and free radicals.
Research Needs 6.9—(1) Model and measurement studies to provide guidance in the
choice of particle mixtures for toxicologic research. (2) Models and measurements
designed to assess the significance of chemical reactions occurring in or on particles for the
chemistry' of the atmosphere.
6.3.6 Collection and Characterization of Particulate Matter for Toxicological
Studies
Toxicologists need samples of collected ambient particles for use in instillation studies,
human clinical and laboratory animal exposure studies with resuspended particles, and in vitro
studies. These particles need to be well characterized as to chemical composition. Since there is
a need to characterize the ambient particles and gases used in experiments with concentrated
accumulation mode particles, collection of large amounts of PM in conjunction with concentrator
studies might also be an effective approach.
Research Need 6.10—Large quantities of well characterized particulate matter are
needed for toxicological studies.
91
-------
documented the potential toxicity of dissolved transition metals. Their solubility is determined
by their oxidation state, which in turn may be determined by photochemical reactions. The
photochemical oxidation of a large number of organic compounds (e.g., PAHs) also can produce
a wide variety of oxygenated products whose toxicologic properties are unknown. In addition, a
number of recent studies have suggested that chemical reactions occurring in or on atmospheric
particles (e.g., involving sulfates, nitrates, marine aerosols, yellow dust from the Gobi desert) can
exert substantial effects on the oxidizing capacity of the atmosphere. Current understanding of
such reactions is limited. Laboratory and field studies, along with integrative model studies, are
required to assess the importance of these reactions, in particular those involving organic
compounds, transition elements, and free radicals.
Research Needs 6.9—(1) Model and measurement studies to provide guidance in the
choice of particle mixtures for toxicologic research. (2) Models and measurements
designed to assess the significance of chemical reactions occurring in or on particles for the
chemistry of the atmosphere.
6.3.6 Collection and Characterization of Particulate Matter for Toxicological
Studies
Toxicologists need samples of collected ambient particles for use in instillation studies,
human clinical and laboratory animal exposure studies with resuspended particles, and in vitro
studies. These particles need to be well characterized as to chemical composition. Since there is
a need to characterize the ambient particles and gases used in experiments with concentrated
accumulation mode particles, collection of large amounts of PM in conjunction with concentrator
studies might also be an effective approach.
Research Need 6.10—Large quantities of well characterized particulate matter are
needed for toxicological studies.
91
-------
6.4.1 Exposure Models
Research Need 6.11—The extensive personal exposure studies described in Research
Need 6.3, that relate ambient concentrations to personal exposure to ambient PM/gases
need to be augmented with exposure activity patterns, from experimental measurements
and surveys, and used to develop exposure models for various situations, populations, and
sub-population groups, including susceptible sub-population groups.
6.4.2 Concentration Measurements
Research Need 6.12—An extensive monitoring program is needed to provide the
ambient concentration data needed to use with exposure models to estimate the distribution
of population exposure. Also see Research Need 6.17.
6.4.3 Population Exposure Studies
Research Need 6.13—An extensive field study of personal exposure is needed to
evaluate the distribution of personal exposure to ambient PM (including its hazardous
subcomponents). These results should be compared with predictions from personal
exposure models to evaluate the ability of models to predict the variation in personal
exposure to ambient PM and its components.
6.4.4 Estimation of Concentration and Exposure Parameters for
Epidemiologic Studies
6.4.4.1 Temporal Variability in Concentration
Statistical associations between PM and health outcomes would be much easier to
determine if a pollution episode of one or several days duration were followed by several days of
relatively clean air. This would make it possible to separate health outcomes from one episode,
some of which have a 3 to 5 day lag, from health outcomes due to the previous episode.
Information on episodicity is needed from a number of major cities to determine to what extent
such situations exist. If a major city with high episodicity could be identified, it would be a
candidate for extensive exposure assessment to support epidemiology. Visibility data has been
used to demonstrate a geographic variation in episodicity of visibility and presumably of fine
93
-------
particle concentration and could be used as a screening tool in the site selection process, followed
by direct monitoring of various PM parameters, including, at a minimum, fine- and coarse-mode
PM. It also would be useful to find cities where some episodes are dominated by fine-mode PM
and others by coarse-mode PM.
Research Need 6.14—Conduct a study of temporal variation in fine- and coarse-mode
PM and other PM components or parameters to identify candidate cities for future PM
time-series epidemiologic studies.
6.4.4.2 Spatial Variability
In time series epidemiology done to date, the exposure in each time unit has been treated as
though it were equal within the community under study. Some information is available to
indicate that PM2 5 and sulfate, especially in the summer in the northeastern United States, are
reasonably uniform within large cities and even over regional areas on the order of hundreds of
miles. Less information is available on coarser fractions of PM, on components other than
sulfate and acidity, for seasons other than summer, and in cities outside the Northeast. Year-
round monitoring may not be required to determine spatial variability. Daily measurements over
at least a month several times a year should be adequate.
Research Need 6.15—Monitoring studies, supported by modeling, need to be
undertaken, with enough measurement sites to characterize the degree of spatial
homogeneity within communities or larger regions, in several areas in different parts of the
United States, to identify candidate cities for future PM time-series and cross-sectional
studies.
6.4.4.3 Long-Duration Measurements
As stated above, the knowledge of the variability in aerosol size distribution and
composition, and the spatial and temporal variability are so poorly characterized that even
short-term studies will provide useful data. However, to capture the full range of variance, it
would be desirable to conduct longer term studies, especially in key locations being used in
epidemiologic studies.
94
-------
Research Need 6.16—Long-term monitoring studies to determine the full range of
variance of size-distribution and composition and spatial and temporal variation.
6.4.5 Integration of Regulatory and Research Monitoring Programs
Many of the existing epidemiology studies have relied on compliance monitoring networks
run by local control agencies for their exposure assessment data. Policies and procedures need to
be developed to make better use of facilities and personnel in local control agencies. Such
agencies should be able to collect monitoring data that will satisfy regulatory needs and also
provide concentration data adequate for use in determining exposure and in the development and
setting of standards. Integration of research monitoring with local agency compliance
monitoring, especially by cooperation with universities or contractors that would use the data in
research programs, would be of mutual benefit in providing additional funds to local agencies,
giving local agencies access to state7of-the-art instrumentation and techniques, reducing costs,
and increasing the reliability of monitoring networks.
The Office of Air and Ratiation (OAR) through the Office of Air Quality Planning and
Standards (OAQPS), plans an extensive expansion of the regulatory monitoring program
including PM2 5 monitoring at up to 1500 sites and chemical characterization of several PM
component species at 50-300 sites. OAR also expects to support intensive studies beyond
routine monitoring, including size distributions and more detail on chemical species.
Research Need 6.17—Research scientists interested in PM exposure, epidemiology
and toxicology' should interact with OAQPS staff planning the regulatory monitoring
network and influence decisions on location of regular, speciation, and super sites and on
the PM parameters and components to be measured at each type of site. In some cases it
may be desirable to augment compliance monitoring networks run by local control
agencies to provide concentration and composition data suitable for exposure assessment
and other research studies.
95
-------
6.5 MEASUREMENT/MONITORING TECHNIQUES
Key Question: What improvements in measurement technology are needed in order to
conduct better exposure and other measurement/monitoring programs?
6.5.1 Measurement of Fine-Mode Particles and Coarse-Mode Particles as
Separate Pollutants
Techniques are needed that cleanly separate fine- and coarse-mode particles and collect
them independently. To determine the most appropriate cut-point size for a national network,
measurements of particle size distributions need to be made in various parts of the country.
Fine-particle components tend to be more hygroscopic than those of coarse particles, so, as
relative humidity increases, fine particles increase in size. Studies using impactors find that at
very high relative humidity, the overlap between fine and coarse particles is greater. These
observations need to be confirmed by studies in which size distributions measured by impactor
techniques are compared with size distributions determined by techniques that provide for in situ
counting of individual particles. These studies need to include measurements of the variation of
particle size as a function of relative humidity. Treatment techniques, prior to separation by
particle size, that reduce relative humidity by removing particle-bound water, but without
removing other semivolatile components, provide a possible mechanism for reducing the overlap
of fine and coarse particles. Once the appropriate size cut has been established, inlet and
impactor systems to collect the specified sizes will need to be developed.
Research Need 6.18—The cut-point size and separation techniques that best separate
fine-mode PM from coarse-mode PM need to be established and standardized.
6.5.2 New Measurement Techniques for Particulate Matter Parameters for
Which Existing Measurement Techniques Are Inadequate
Neither routine monitoring, nor well-developed research techniques are available for
measurement of the following important PM components or characteristics.
(1) "Suspended" Mass, (i.e., mass of PM suspended in the air, including the mass of condensed
phase components in equilibrium with gas-phase components [e.g., semivolatile organic
compounds and ammonium nitrate] but excluding the mass of particle-bound water). EPA
96
-------
has funded three grants with the goal of developing such techniques. However, no methods
have yet been proven to be satisfactory. "Dried" particle mass can be measured with high
precision (CV < 10%). However, drying treatments which involve equilibration at low
relative humidity (Federal Reference Method for PM10 and PM2 5) or heating particles on
the filter to higher than ambient temperature (TEOM® and some beta-gauge techniques) to
remove particle-bound water also may cause loss of some semivolatile PM. Semivolatile
PM is also lost from the filter during the sampling process, both due to pressure drop across
the filter and concentration changes during sampling. Samples from the eastern U.S. appear
to retain some particle-bound water (perhaps associated with H2SO4), whereas samples
from all locations retain some, but not all, semivolatile organics and ammonium nitrate.
(2) Cleaner Separation of Fine- and Coarse-Mode PM. Fine- and coarse-mode PM overlap in
the region 1.0 to 3.0 um aerodynamic diameter. In general, coarse particles can be smaller
in very dry areas. Fine particles can grow to larger sizes when the relative humidity is very
high. PM2 5 will capture almost all fine mode PM, even at very high relative humidity.
Hence PM2 5 is considered by EPA to be an appropriate fine particle indicator for
compliance monitoring. (It is also the only fine mode indicator for which significant
amounts of data exists.) However, PM2 5 may not be ideal for epidemiologic studies or
source-category apportionment. Potassium may be from soil (coarse) or from wood burning
(fine), iron may be biologically active iron from combustion sources (fine) or less
biologically active iron from soil (coarse). Unless fine- and coarse-mode mass are highly
correlated, the combination of both in PM2 5 and the removal from PM/10_2 5) of that portion
of coarse-mode mass that has the highest deposition in the lung will reduce the ability of
epidemiological studies to find statistical correlations of PM2 5 and PM(10_2 5) with health
outcomes and to differentiate between the health effects of fine and coarse particles.
(3) Ultrafme particles. Ultrafine is used to refer to particles in the nuclei mode in the
atmosphere or to any distribution of particles with a mass mean diameter below 0.1 um.
Total number of particles (which is usually dominated by particles below 0.1 um diameter)
or the number of particles in any given size range can be measured. However, for
toxicological purposes, it would be desirable to have information on the chemical
97
-------
composition of ultrafme particles and to measure soluble and insoluble ultrafine particles
separately.
(4) "In-situ aerosol". Ambient particles, in equilibrium with the pollutants in ambient air,
contain a variety of potentially toxic gases dissolved in particle-bound water, the liquid
water associated with the particle. Such particles are called "in-situ aerosol" to differentiate
them from particles generated from laboratory chemicals or particles collected from the
ambient air, dried and redispersed (laboratory particles). The chemical composition and
morphology of in situ aerosol particles need to be studied. A variety of species may be
dissolved in the particle-bound water including hydrogen peroxide, formaldehyde, formic
acid, organic peroxides, and ozonides. Some of these species may be biologically,
chemically, or photochemically active. The dissolved species, if present in the gas phase,
would be largely removed by deposition to wet surfaces in the upper respiratory system.
However, when dissolved in particles, they can be carried deep into the lung. The structure
of such particles, which may include an insoluble core and an organic outer film, need study.
Methods will also be needed to measure the quality of particle-bound water.
(5) Primary Biological Aerosol Particles (PBAP). PBAP refers to airborne particles that are, or
were derived from, living organisms, including microorganisms and fragments of all
varieties of living things (e.g. bacteria, viruses, pollen, mold spores, and fragments of insects
and plants). PBAP are known to cause immunologic responses and to be present in particles
greater than 2.5 um diameter. Recent studies, however, suggest that significant amounts of
PBAP may be found in the size range below 2.Sum diameter and even below 1 .Oum
diameter. Techniques need to be developed and applied to determine the concentration,
sources, and biological properties of PBAP. Information is needed for both ambient and
indoor PBAP in the size range below lOum diameter and especially in the size range below
2.Sum and l.Oum diameter.
(6) Organic Fraction. The atmospheric aerosol contains a complex mixture of nonvolatile and
semivolatile organic compounds. Only a small fraction (10 to 20%) of the organic aerosol
has been identified and quantified. Many organic compounds, particularly polar organic
compounds, which are more oxygenated and more likely to be bioavailable, have yet to be
identified. More complete characterization of the organic aerosol is needed. Methods are
98
-------
needed to analyze the organic fraction by compound class in a way that is chemically or
toxicologically meaningful. Such information would provide a framework for
epidemiologic and toxicological studies of organic constituents.
(7) Dissolution and Bioavailability. The dissolution and bioavailability characteristics of PM
for various origins, components, and sizes are important for determining the rate at which
material is available for reaction in respiratory tract fluids and the retention time in the
respiratory tract. As a first step, a technique for determining the in vitro dissolution rate of
PM and PM components would be useful. This important aspect of the physical/chemical
evaluation of PM would be useful in modeling the accumulation patterns and magnitude of
respiratory tract burdens of PM from chronic exposure.
(8) Ammonium Nitrate. Ammonium nitrate concentrations are known to make a significant
contribution to aerosol mass in the western and central United States. However, except for
the IMPROVE visibility network and measurements made with annular denuders, most
measurements significantly underestimate the concentration of ammonium nitrate.
Therefore, information is needed on the concentrations and spatial and temporal variability
of ammonium nitrate. Nitric acid, formed in the atmosphere from NOX emissions, will form
particulate ammonium nitrate when there is an excess of ammonia over that needed to form
ammonium sulfate from sulfuric acid formed from SO2 emissions. Because SO2 emissions
in the eastern United States are scheduled for continued reductions, the concentration of
ammonium nitrate in the eastern United States may increase in the future.
Research Need 6.19—Better techniques need to be developed for characterizing the
composition and distribution of selected important ambient PM components or
characteristics for which adequate measurement techniques have not yet been developed:
"suspended" mass, fine- and coarse-mode mass, ultrafme particles, "in situ aerosol",
PBAP, the organic fraction, dissolution and bioavailability characteristics of PM, and
ammonium nitrate.
6.5.3 Measurement of the Semivolatile Components of Particulate Matter
Particulate matter is defined by the current FRM as the material left on a filter after
equilibration for 24 h at a temperature of 15 to 30 °C and a relative humidity of 25 to 40%.
99
-------
There are no specifications as to the temperature of the filter (and the PM on it) during collection
or between collection and equilibration. The main purpose of the equilibration process is to
remove water absorbed by the filter material and particle-bound water. The equilibration process
results in the loss of most of the absorbed and particle-bound water, although it is likely that not
all particle-bound water is removed from acidic PM. The process also results in the loss by
evaporation of a significant but an indeterminate fraction of ammonium nitrate, some
components of woodsmoke, and other semivolatile material.
The FRM for the new PM2 5 standard has tighter specifications for equilibration conditions
and will limit the allowable temperature increase above ambient during and after collection. This
may improve the precision of the method but will not remove the uncertainty in mass due to
partial loss of semivolatile components.
Semivolatile materials such as ammonium nitrate, woodsmoke components, and
semivolatile organic compounds are important in terms of their contributions to both particle
mass and potential health effects. Therefore, information on such materials is needed for future
epidemiological and toxicological studies and also needs to be available for consideration in the
next revision of the PM standard. A key problem is the development of a PM collection
technique that provides for the removal of particle-bound water without the loss of semivolatile
organic components such as components of woodsmoke or semivolatile inorganic compounds
such as ammonium nitrate.
Research Need 6.20—Development of sampling, collection, and storage techniques
that will permit collection of PM with removal of particle-bound water but without loss of
SVC, both for mass determination and for subsequent chemical analysis.
6.5.4 Continuous and Long-Time-Interval Samplers Need To Be Developed
for Particulate Matter Parameters for Which Existing Measurement
Techniques Are Adequate
Routine monitoring or well-developed research techniques are available for the following
components.
(1) "Dried mass": mass remaining after particles are collected on a filter and dried by various
techniques that remove both particle-bound water and other semivolatile components.
(2) Particle number (research techniques).
100
-------
(3) Particle size distribution (research techniques).
(4) Major components of mass: sulfate, nitrate, hydrogen, and ammonium ions; elemental and
organic carbon; and crustal and trace elements. A significant amount of information on
spatial and temporal distribution is available for sulfate and crustal elements only.
(5) Specific components for which biological effects hypotheses have been advanced: hydrogen
ion and transition elements.
(6) Gases that are possible confounders or cofactors: ozone, carbon monoxide, sulfur dioxide,
and nitrogen oxides.
Research Need 6.21—Development of techniques for continuous measurement and for
collection of weekly to monthly samples for the above parameters. Determination of their
spatial and temporal distributions.
6.5.5 Time Resolution of Particulate Matter Measurements
Acute and chronic PM epidemiology have different analytical-techniques requirements for
exposure assessment. Three levels of time resolution are needed for research studies: (1) long-
term integrated measurements (weeks to months) are needed for epidemiologic studies that
compare life expectancy or chronic health effects in different cities; (2) 24-h average
measurements are needed because most acute health outcomes are measured on a daily basis; and
(3) continuous measurements are needed to determine if peak concentrations, 24-h integrated
concentrations, or concentrations integrated over shorter time intervals are related more closely
to acute health effects.
Research Need 6.22—The various continuous monitoring techniques need to be
intercompared with each other and with 24-h, integrated collection techniques in various
parts of the country with different types of PM. Similarly, long-term monitors, which
integrate a sample over several weeks, need to be compared with 24-h integrated
measurements under the same range of conditions. Standard operating procedures and
quality control protocols need to be established for both types of monitors.
101
-------
6.5.6 Monitoring/Measurement Situations
The measurement techniques discussed above need to be developed or adapted so that they
apply to a variety of monitoring/measurement situations.
Research Need 6.23—Methods need to be developed, for the PM parameters and
components discussed earlier, that can be applied to personal exposure and indoor air
characterization as well as to central site monitoring and compliance monitoring.
6.5.7 Precision of Measurement Techniques
When statistical techniques are used to model the association of health outcomes with
a series of pollutant measurements, the effects of the less precisely measured species may be
attributed to the more precisely measured species if the two are correlated. Effects cannot be
reliably attributed to species measured with poor precision in statistical associations using
several variables. This can be very important in decisions as to which components to regulate.
Research Need 6.24—Precision must be carefully determined for measurement
techniques used to collect exposure data for epidemiologic studic:. In order to ensure the
maximum possible precision and to maintain high precision throughout a long
measurement program, SOP and quality assurance and control protocols will need to be
developed and followed.
6.5.8 Measurement of PM2>5 for Determining Compliance Status
A new Federal Reference Sampler and Procedure, for determining compliance with the new
PM2.5 standard, including SOP and QA/QC protocols has been developed. Local pollution
control agencies will need to use this method to initiate monitoring programs to determine if they
are in compliance with the new PM2 5 standard.
Research Need 6.25—Field studies in several parts of the country arc needed to
determine the precision of the new Federal Reference Method and to intercompare it with
other 24-h samplers and with weekly and continuous monitors.
102
-------
6.6 AMBIENT CHARACTERIZATION AND MODELING
6.6.1 Air Quality Models for Aerosols
Models can be useful tools for characterizing the spatial and temporal variability of
ambient aerosol concentrations, size distribution, and composition for use with exposure models
for estimating exposure to various aerosol components in a given airshed. These
characterizations of the variability of aerosol components could be used in the planning of
epidemiologic studies, and in the analysis of results from past studies. Future epidemiologic
studies may examine the health effects of individual chemical species (e.g., sulfate, nitrate) or
groups of covarying species (e.g, transition metals, crustal elements, organic carbon) constituting
PM. Alternatively, future studies may examine the health effects of constituents with widely
dispersed regional-scale sources compared to those generated on more localized scales. Models
can be used to help select communities with epidemiologically appropriate mixes of PM arising
from remote and local sources. They can also be used to assist in the identification of specific
communities for studies intended to characterize and compare health effects of PM produced by
different local sources, as well as aiding in monitoring site selection. In addition, models can be
used to evaluate ecologic exposure data in past epidemiologic studies by characterizing the
degree of homogeneity in community wide exposures to PM components, and by characterizing
the long-term temporal stability of patterns of exposure to PM components. Models might also
be used to increase the number of usable time units in past or future studies by providing
modeled PM exposures for time units, during which those exposures were not measured.
There are a number of factors that have limited the development of accurate aerosol
models. A number of important chemical and physical processes have not been adequately
characterized experimentally or were not incorporated into available models. Emissions from
major sources of primary PM or from major sources of gaseous precursors to secondary PM
formation have not been well documented in many cases. Indeed, many major sources are not
even identified. Meteorological processes often have not been accurately modeled and
incorporated into numerical codes. Because of computational demands, it is often too expensive
and time consuming to incorporate detailed chemistry and aerosol microphysics modules into
chemical tracer models. Instead, only versions incorporating parameterizations of complex
103
-------
processes can be used. This is often the only feasible way to assess the effects of atmospheric
transformation processes on the composition of emissions from various sources.
However, these parameterizations should be based on well-defined physical and chemical
processes and should contain sufficient detail for comparisons to field measurements and for
precise predictions of size-dependent aerosol properties. The aerosol modules should be flexible
enough to be used in a number of applications including the three-dimensional modeling of the
urban and regional scale distribution of fine and coarse aerosol components and their precursors
and in much smaller scale models to determine the exposure characteristics of particles emitted
from local sources. The larger scale models can be used to determine the day-to-day variability
in components with widespread regional sources (e.g., sulfate) in urban airsheds. The smaller
scale models can be used to determine the short-term evolution of the size distribution and
composition of the aerosol emitted by local sources (e.g., motor vehicle exhaust) and the
infiltration of the ambient aerosol to indoor environments. All these improvements in the
formulation and computational efficacy of PM models will require the careful design,
implementation, and analysis of laboratory and field experiments. These experiments should be
designed in concert with model developers and experimentalists.
Research Needs 6.26—Models capable of calculating the urban- and regional-scale
distribution of major PM components and their precursors, along with methods to evaluate
their performance, need to be developed. Aerosol microphysics and chemistry modules
suitable for calculating the evolution of the size distribution of aerosols in chemical tracer
models need to be developed. Parameterizations for the condensation and volatilization of
vapors and the coagulation and sedimentation of particles along with the chemical
transformations occurring within particles should be included. Computationally
inexpensive, user-friendly three-dimensional trajectory models, which can incorporate
varying degrees of complexity of basic aerosol chemistry and microphysical processes, need
to be developed. Models capable of calculating exposures to highly variable emissions from
localized sources also need to be developed and evaluated. Much more refined treatments
of transport processes in urban boundary layers are needed before this can be done.
Comprehensive urban/regional field studies arc needed that can be used to evaluate the
performance of existing and future PM air quality models.
104
-------
6.6.2 Emission Inventories
Emission inventories are required for air quality models of gas and aerosols. The
uncertainty in emissions inventories for PM components from both natural and anthropogenic
sources needs to be reduced. Emissions of SO2, NOX, and most gaseous hydrocarbons are
covered in other programs and will not be addressed in this document.
Emission rates of fugitive dust are highly uncertain. In situ and remote sensing techniques
for improving estimates of emissions raised by either natural or anthropogenic processes need to
be developed. Questions about the size distribution of the aerosol suspended by a number of
dust-raising processes remain. A number of studies in the past have been carried out with
impactors that may be subject to particle bounce, resulting in the intrusion of coarse-mode
particles into finer fractions and an overestimation of the fine fraction. With the advent of a
PM2 5 standard it will become very important to accurately determine the amount of fine PM in
fugitive dust. Measurements with particle counting and sizing devices that avoid the
uncertainties of impactor measurements will be required. Additional studies are needed using
techniques that count individual particles by size and avoid particle-bounce problems. The
extrapolation of results from studies conducted at specific sites to larger spatial scales is also of
concern. The accuracy of available data may also be tested by performing regional-scale model
simulations of dust concentrations.
Elemental carbon and organic carbon emissions from in-use motor vehicles are uncertain.
A high degree of variability in emissions of these species is expected across the motor vehicle
fleet. Remote sensing of total aerosol emissions from motor vehicles may be a useful approach
for reducing uncertainties in mobile source emission inventories. Emissions factors and
inventories for sources of carbonaceous species do not yet include inputs for a number of sources
(e.g., cooking).
Several aspects of emission inventories currently are not well characterized or understood.
Biogenic emissions, which lead to secondary organic carbon formation are also uncertain.
Marine aerosols and aerosol precursors are also important contributors to aerosol concentration
in coastal areas, but information about their sources is either completely lacking or poorly
defined. Emissions of ammonia are also highly uncertain.
105
-------
Research Needs 6.27
(1) Developing and evaluating emissions inventories for primary PM components, for
example:
• fugitive dust (industrial, mining, agriculture, and paved and unpaved road dust),
• elemental carbon and organic carbon particles (gasoline- and diesel-fueled vehicles
and biomass burning), and
• metals (from high temperature and other sources).
(2) Modeling dust resuspension processes and developing techniques for evaluating dust
emissions estimates.
(3) Developing and evaluating emissions inventories for secondary PM components, for
example:
• NH3,
• natural and anthropogenic organic compounds that form particles on
photooxidation, and
• marine aerosols and aerosol precursor gases.
(4) Developing and evaluating techniques for measuring particulate emissions from motor
vehicles operating under real-world conditions.
(5) Inverse modeling techniques also should be applied to the evaluation of emission
inventories.
6.6.3 Source Apportionment of Ambient Particulate Matter
Chemistry and transport models are based on a prognostic approach for calculating aerosol
concentrations. In contrast, receptor models adopt a diagnostic approach by which contributions
to ambient aerosol samples from different source categories are inferred. Inverse modeling
techniques, which rely on winds and chemical transformation rates from chemistry and transport
models to infer source contributions, may see expanded use in the future. Both receptor and
chemistry and transport models are used most frequently to determine the best control techniques
to meet standards. However, source apportionment could be used for a different purpose.
It would be possible to develop a time series of daily contributions of various source categories
to ambient PM concentrations and exposures for use in acute epidemiologic studies (or source
106
-------
contribution in different cities for chronic studies). Such analyses might provide information on
the relative health effects of various PM sources.
6.6.3.1 Source Apportionment Techniques
Most receptor modeling methods have been developed for apportioning sources of primary
PM components with the notable exception of PBAPs. Much less work has been done in
deriving methods for apportioning secondary species (species formed from chemical reactions of
gaseous precursors in the atmosphere (e.g., SO4=, NO3~, NH4+, organic carbon), which can
constitute the major fraction of fine particulate mass in many locations. In addition, source
apportionment analyses are typically performed across a broad range of particle sizes (e.g., on the
PM2 5 or on the PM10 size fractions). Little work has been done on subsets of these broad classes
such as the ultrafine size fraction.
Single particle analyses, based on scanning electron microscopy (SEM), can provide useful
data concerning the nature of individual particles. SEM analyses can be used to design
toxicologic studies based on the morphology and chemistry of single particles. SEM analyses
also can be used to discriminate between particle sources when there are collinearities in source
composition that cannot be resolved by receptor modeling methods applied to bulk analyses of
filter samples.
Research Needs 6.28—(1) Methods to identify PBAP in ambient samples and to
incorporate them into source apportionment analyses. (2) Measurements of profiles of
sources of secondary PM components. (3) Further development of modeling techniques for
apportioning secondary species such as SO4=, NO3", NH4+, and secondary organic carbon.
(4) Size resolved source apportionment analyses of ambient particle samples. (5) Methods
to characterize the composition and morphology of individual particles.
6.6.3.2 Composition of Primary Emissions
The chemical composition of emissions from many major sources of primary PM is poorly
known. As an example, the composition of motor vehicle emissions is still characterized too
poorly to be used to determine motor vehicle contributions to PM2 5 concentrations in source
apportionment analyses. Organic compounds, which might be used to distinguish between
107
-------
gasoline and diesel exhaust, or between motor vehicle exhaust and other sources of elemental and
organic carbon (e.g., vegetation and fuelwood burning, cooking), are not used widely in source
apportionment studies. Instead, emissions from these sources are often lumped into ill-defined
categories such as organic carbon.
Research Need 6.29—Techniques for speciating emissions of organic compounds
suitable for use in source apportionment analyses are needed. The systematic compilation
of chemically speciated data from a wide variety of primary PM sources is also needed.
6.6.3.3 Time Series of Source Category Contributions
A number of studies suggest that specific PM components may be responsible for reported
associations between ambient particulate levels and health effects. Many studies have
investigated the toxic effects of specific substances. Alternatively, the effects of toxic agents
emitted by specific sources can be examined. The latter approach involves the construction of
daily time series of source contributions to ambient particles based on analysis of long time
series of daily filter samples. The daily time series of source contributions to ambient PM can
then be compared with epidemiologic time series of various health endpoints.
Research Needs 6.30—(1) Techniques for providing daily time scries of specific source
contributions for use in acute epidemiologic studies. (2) Methods for relating source
contributions to ambient PM with time series of mortality.
6.6.4 Secondary Organic Particulate Matter Formation
Because a large fraction of fine mode mass is secondary, distant sources can have a large
potential for contributing to local ambient PM concentrations. A number of physical and
chemical processes occur during transport from sources to receptor sites that determine the
composition and size distribution of the transported aerosol. These processes result in the
formation of secondary particulate matter, and also can influence the toxicologic properties of the
aerosol. Formulations for many chemical processes involved in these transformations are still at
an inadequate stage of development for incorporation into urban and regional scale models.
Chemical processes resulting in the formation of secondary organic aerosol products are
especially uncertain. Smog chamber studies of the fractional yield of secondary organic carbon
108
-------
produced by the oxidation of a number of anthropogenic and natural hydrocarbons have been
performed. However, fractional yields of carbon transformed into secondary organic aerosol
measured in these studies are highly variable and results from individual studies are not always
consistent. Secondary organic particulate compounds can be formed either from the
condensation of an organic gas that has reached its saturation vapor pressure, from the absorption
of a soluble organic compound into a liquid-coated particle, or from the adsorption of an organic
gas on the surface of a particle. The composition of aerosol products has not been determined in
many studies, hindering the development of chemical mechanisms that could be used to interpret
the experimental results.
Research Need 6.31—A more detailed understanding of aerosol microphysical and
chemical processes, which govern secondary aerosol size distribution and composition
needs to be developed through laboratory, field, and modeling studies. Better data are
needed to describe the fractional yield of secondary organic aerosol formation from the
oxidation of natural and anthropogenic hydrocarbon precursors. Data also are needed to
elucidate the mechanisms that lead to the formation of secondary organic PM (i.e., vapor
saturation, absorption, adsorption). This will require both laboratory and field
investigations of the nonvolatile and semivolatile fractions of the organic component of
aerosols as well as the development of methods to analyze the composition of reaction
products. Experimental and theoretical studies of the absorption of water-soluble organic
compounds are also needed.
6.7 BACKGROUND CONTRIBUTIONS TO PARTICULATE MATTER
CONCENTRATIONS
A knowledge of background sources of PM and corresponding concentrations is required
for regulatory purposes and for performing risk analyses. There are a number of ways to define
background levels. The two chosen as most relevant in the recently completed PM AQCD and
Staff Paper include contributions from uncontrollable sources that can affect PM levels in the
United States. The first definition includes anthropogenic and natural sources outside North
America and natural sources within North America, and the second includes only natural sources
109
-------
within and outside North America. Methods are needed to estimate the highest annual 24-h
average background value and the annual average background value for different regions of the
United States. Annual average background levels were used to correct ambient concentrations in
the calculations assessing risk of mortality due to PM exposure. It is also necessary to know
background levels on days when 24-h standards may be exceeded. Background values should be
constructed for different aerosol components (ammonium, nitrates, sulfates, organic carbon,
elemental carbon, and dust).
Although anthropogenic SO2 and NOX emissions are relatively well known, information
concerning the strengths of natural sources of these gases (e.g., dimethyl sulfide and SO2 from
natural sources and NO from soils and vegetation burning) is relatively sparse. Emissions of
these species constitute a natural source of precursors of secondary PM. Episodic natural sources
either within or outside the United States often contribute to elevated ambient PM levels. These
sources include the long-range transport of dust from North Africa and the transport of dust from
one region of the United States to another during dust storms. Forest fires represent another
highly episodic source of PM. However, it is still not clear to what extent these sources result
either directly or indirectly from anthropogenic activities.
Research Needs 6.32
(1) Emissions inventories for uncontrollable sources of fine- and coarse-mode PM and
PM components within and outside North America.
(2) Emissions inventories for uncontrollable sources of gaseous precursors to secondary
PM formation within and outside North America.
(3) Chemical tracer models capable of providing estimates of the background levels
defined above.
(4) Field studies designed to determine regional background PM levels. Modeling studies
should be pursued in conjunction with the field studies to infer anthropogenic
contributions to observed PM levels.
(5) Methods to use historical visibility and turbidity observations, or other data, going
back to the mid-20th century to determine the evolution of fine PM pollution to
current levels.
(6) Methods to determine the extent of human influences on episodic PM sources.
110
-------
6.8 INDIRECT HEALTH EFFECTS RELATED TO CHANGES IN
PARTICULATE MATTER LEVELS
In addition to the research described above in this document, some effort should be devoted
to examining changes in atmospheric properties, which may result from changes in ambient PM
levels, and the effects they might have on human health. As an example, the transmission of
solar UV-B radiation is controlled by the overhead column abundance of ozone in the
stratosphere, tropospheric components such as cloud droplets and aerosol particles, and ozone.
Solar UV-B radiation reaching the surface has been linked to skin cancer, cataract formation and
immunosuppression. In addition, solar UV-B radiation is linked to ecological effects and to the
photochemical formation of ozone and secondary PM. As another example, particles mainly
reflect solar radiation back to space. The effect of particles on the climate system has been
estimated to be large enough to offset the warming effect of the so-called greenhouse gases
(e.g., CO2, CH4, chlorofluorocarbons) on a globally averaged basis. However, the aerosol effects
are localized and vary significantly with time and location, whereas the effects of the greenhouse
gases are more uniform around the globe. Research into the climatic effects resulting from
changing emissions of aerosols and greenhouse gases and into the health effects of climate
change (e.g., through altered ranges of infectious diseases, direct thermal effects) will probably
be carried out at federal agencies other than EPA.
Changes in fine particle concentrations also may affect the size distribution of the
remaining aerosol, especially in the ultrafine size mode. The abundance of ultrafme particles is
determined primarily by the rate of generation. However, removal of ultrafme particles is
controlled by coagulation with particles in the accumulation mode. Hence, for the same
generation rate, changes in the total surface area of accumulation mode particles may result in
changes in the number of ultrafine particles.
Research Needs 6.33
(1) The effects of particles and gas phase pollutants on the transmission of UV-B radiation
through the atmospheric boundary layers over major urban areas in the United States
compared to those over rural areas needs to be determined.
(2) The effects of particles on photolysis rates and formation rates of ozone and secondary
PM need to be determined.
Ill
-------
(3) Effects of changes in fine PM levels on the overall aerosol size distribution need to be
determined.
6.9 GENERAL PRINCIPLES
(1) New PM measurement techniques will be needed to provide exposure indices for
epidemiologic studies and to determine personal and community exposure to ambient
particles. During the next 5 years, compliance monitoring will feature extensive
measurements using the new Federal Reference Method (FRM) for PM2 5. The new FRM
for PM2 5, like the current FRM for PM10, will require equilibration at a fixed temperature
and a low relative humidity in order to remove most of the particle-bound water. However,
the sampling and equilibration process causes the loss of an unknown, but probably
variable and significant, fraction of semivolatile material (SVM) such as ammonium
nitrate, components of woodsmoke, and other soluble and condensible organic compounds.
Therefore, new PM measurement techniques need to be developed that include SVM as
part of PM mass and that collect SVM in order to better characterize this poorly understood
component of ambient PM. Attention should be given to precision, accuracy, ease of use,
and cost. New techniques need to be designed for outdoor, indoor, and personal monitors.
Cost of monitors and sample analysis is important because of the large number of sites and
measurements that will be needed. Precision may be determined by intercomparison of
identical, collocated monitors. However, no absolute determination of the accuracy of PM
measurements is possible because there is no standard for dispersed, ambient PM.
Qualitative information about accuracy can be obtained by comparison of different,
collocated measurement techniques. Techniques, which are acceptable to the broad
scientific community, with standard operating procedures (SOPs) and quality
assurance/quality control (QA/QC) protocols, are needed to separate fine mode and coarse
mode particles as cleanly as possible and to determine particle mass and a variety of
particle parameters and components.
(2) New exposure assessment studies should measure fine-mode PM and coarse-mode PM
as separate pollutants. Up to now, scientific and regulatory concern has focused on
112
-------
PM2 5. However, current understanding suggests that the need is not so much for
separation at a specific size but for separation of fine mode PM from coarse mode PM
based on the different composition and sources of the two modes. It may be that a smaller
size cut, perhaps proceeded by a dehumidification process, would give a better separation
of fine and coarse PM.
(3) Planning for major, new epidemiologic and exposure assessment studies should be
coordinated with the development of improved measurement technologies for the
measurement of fine- and coarse-mode particles, including semivolatile components.
Thus, improved methods, samplers, etc., which have been characterized, intercompared,
and demonstrated to provide reliable data, will be available for new studies. Measurements
of specific PM components, including PM, 0, PM2 5, PM,0_2.5, sulfate, acid, etc., in
addition to PM)0 or TSP only, will be useful for determining the suitability of communities
for epidemiologic studies in terms of spatial and temporal gradients. Ongoing studies that
measure indicators of fine mode particles should be completed and existing data bases
containing PM2 5 should be analyzed. However, it is important that improved exposure
indices, which include fine- and coarse-mode particles, specific constituents of PM and
information on the relationships between ambient concentration and personal exposure to
particles of ambient origin, be used in new epidemiologic studies.
(4) Exposure assessment studies should support and be coordinated with epidemiologic
studies or other health studies, or with source apportionment, model evaluation, or
physical or chemical process studies. If health effects are understood and a concentration
level that requires action can be specified, exposure studies independent of health studies
can be useful. However, whenever possible, exposure and health studies should be
coordinated. Exposure studies, independent of health studies, are appropriate in some
instances. However, such exceptions should be analyzed to determine if they could be
coordinated with health risk assessment studies.
(5) More consideration needs to be given to the relationship between concentration and
exposure. The relationship between ambient concentrations and personal or community
exposures is complex and controversial. Community-level, acute epidemiologic studies,
which relate daily variations in health outcomes to daily variations in ambient
113
-------
concentrations in the community, usually use daily concentrations given by a central
monitor to represent a daily concentration that is the same everywhere in the community.
It is also possible to average several monitors and assume that this represents the average
community concentration. However, if the variation in concentration across the
community is too great or if the concentrations at different sites in the community are
poorly correlated, the health effects may be averaged out as well as the concentration, and
any relationship between PM and health outcomes will be difficult to characterize.
Also, total exposure is the combination of exposure to particles in ambient air while
outdoors, to ambient air particles that have penetrated indoors, and to particles that have
been generated indoors, and to particles related to personal activities. Therefore, exposure,
whether personal or community, and whether to total or to ambient pollutants, will depend
on the amount of time spent indoors or in other microenvironments. This dependence
occurs because the concentration of ambient pollution is generally less indoors than
outdoors and depends on the type of pollutant and the particle size. Sensitive populations,
such as infants, active children, asthmatic children, elderly individuals, COPD patients,
persons with cardiovascular problems, etc., may have different activity patterns and
microenvironmental exposures than normal adults. Special exposure studies may be
needed to determine the relationship between ambient concentration and total exposure to
ambient particles for these or other potentially susceptible subpopulations.
(6) Both ambient particles and particles generated in microenvironments need to be
characterized. Community epidemiologic studies provide information on the association
between health effects and ambient pollution concentrations but probably not on any
possible association of health effects with exposure to indoor-generated or personal-activity
particles, or particles generated in other microenvironments (e.g., homes, cars, stores,
offices, schools, hospitals, etc.). However, there is concern that exposures to such particles
may influence health effects, including long-term health effects such as altered
susceptibility. Therefore, it will be important to characterize the sources, composition and
health effects of particles generated indoors and in other microenviroments as well as
ambient particles.
114
-------
(7) Personal exposure, indoor/outdoor, and ambient/microenvironment studies should
obtain adequate information to differentiate between PM from ambient sources,
including ambient PM that has penetrated indoors or into microenvironments, and
indoor-generated and personal-activity-generated PM. Two approaches have been used
to associate personal exposure with ambient concentrations. The cross-sectional approach,
used most frequently, compares the ambient concentration versus the personal exposure for
many people, but only covers a few days per person. Most such studies yield very low
correlations between ambient and personal because personal exposure varies greatly from
person to person. The only exceptions are a few studies of people with low PM
contributions from indoor sources. The serial approach follows the same person for a
longer period of time and obtains a correlation between ambient concentrations and
personal exposure for that person. Much higher correlations are found with the serial
approach. This would be expected if the day-to-day variations in the indoor concentrations
and concentrations resulting from personal activities (personal cloud) for a specific person
were less than the variations between different persons.
Because the variations in indoor sources and personal-activity sources would not be
expected to correlate well with each other, health effects of indoor and personal activity
sources probably would not show up in statistical associations between health effects and
community concentrations. Because of the lack of correlation between ambient
concentration and indoor plus personal-activity concentrations, the latter should not be a
confounder of the former in epidemiologic studies using ambient community
concentrations as the exposure index. Therefore, total personal exposure is not the best
index for health studies. Personal exposure to PM needs to be partitioned into exposure
due to indoor-sources, exposure resulting from personal activity, and exposure to PM of
ambient origin. PM from ambient sources is not only found outdoors; it penetrates into
indoor spaces and makes a substantial contribution to indoor PM. This partitioning is
needed to identify sources, to relate personal exposure to ambient concentrations, and to
partition health effects to ambient or indoor PM by epidemiology or toxicology.
Although control or mitigation of indoor-generated PM is of concern, that is not the
focus of this report. If indoor-generated PM is a health hazard, EPA may educate the
115
-------
public to the hazard, but EPA has no authority to regulate or control indoor air. However,
certain health effects, especially asthma and allergy, are likely influenced by indoor-
generated particles, especially biological particles. Therefore, more knowledge is needed
about the sources and toxicity of indoor-generated particles. Studies that investigate the
role of ambient pollution (particles and gases) in potentiating the effects of indoor-
generated pollutants on immune responses would be useful.
116
-------
Appendix A
Summary of Key Uncertainties and
Research Recommendations
Section VII-E, Staff Conclusions and
Recommendations on Primary NAAQS
Review of the National Air Quality Standards
for Particulate Matter:
Policy Assessment of Scientific and
Technical Information
OAQPS Staff Paper
EPA-452/R-96-013, July 1996
A-l
-------
SUMMARY OF KEY UNCERTAINTIES AND RESEARCH
RECOMMENDATIONS
Staff believes it is important to emphasize the unusually large uncertainties associated with
establishing standards for PM relative to other single component pollutants for which NAAQS
have been set. The AQCD and this staff paper note throughout a number of unanswered
questions and uncertainties that remain in the scientific evidence and analyses as well as the
importance of ongoing research to address these issues. Prior to summarizing staff
recommendations on the primary PM NAAQS in the next section, this section summarizes key
uncertainties and related staff research recommendations.
(1) One of the most notable aspects of the available information on PM is the lack of
demonstrated mechanisms that would explain the mortality and morbidity effects associated
with PM at ambient levels reported in the epidemiological literature. The absence of such
mechanistic information limits judgments about causality of effects and appropriate
concentration-response models to apply in quantitatively estimating risks. Building on
promising preliminary findings from ongoing research involving more representative animal
models and particle mixes and levels, staff believes there is an urgent need to expand
ongoing research on the mechanisms by which PM, alone and in combination with other air
pollutants, may cause health effects at levels below the current NAAQS.
(2) Uncertainties and possible biases introduced by measurement error in the outdoor monitors,
including both the error in the measurements themselves and the error introduced by using
central monitors to estimate population exposure, contributes to difficulties in interpreting
the epidemiological evidence. To address these concerns, additional research into improved
continuous sampling and analyses methods, together with the use of a research-oriented
ambient monitoring network and personal monitors to better characterize relationships
between personal exposure and outdoor/indoor air quality, is needed for PM components as
well as for other criteria pollutants. For example, monitoring techniques that allow new
epidemiological studies to address not only size fractionation and improved measurements
of semivolatile particles but also particle number and surface area will be important to
isolate key components of fine- and coarse-fraction particles. Further, examination of
potential exposure to ultrafine particles near highways and other possible sources, for
A-2
-------
example, is important to determine the extent to which these materials persist long enough to
present significant exposure to sensitive population groups.
(3) Inherent in epidemiological studies such as those cited in this review is the question as to
whether or to what extent the observed effects attributed to PM exposures are confounded by
other pollutants commonly occurring in community air, such as sulfur dioxide, ozone,
nitrogen dioxide, and CO. In particular, a number of authors conducting reanalyses of
mortality studies within a given city, most notably for Philadelphia, have demonstrated that
it may not be possible to separate individual effects of multiple pollutants when those
pollutants are highly correlated within a given area. Based on its assessment of available
information regarding potential confounding within and across a number of areas with
differing combinations of pollutants, as recommended in the HEI reanalysis report, the CD
concludes that, in general, the reported PM effects associations are valid and not likely to be
seriously confounded by copollutants. Nevertheless, additional research and analyses are
important to better characterize the extent to which PM-related effects may be modified by
the presence of other copollutants in the ambient air.
(4) Although staff has concluded that it is more likely than not that fine fraction particles play
a significant role in the reported health effects associations, identification of specific
components and physical properties of fine particles that are associated with the reported
effects is very important for both future reviews of the standards and in development of
efficient and effective control strategies for reducing health risks. Epidemiological and
toxicological research is needed to isolate key components (e.g., nitrates, sulfates, organics,
metals, ultrafine particles) and characteristics of fine particles, as well as to identify the
nature and extent of subpopulations most susceptible to the adverse effects associated with
such components and characteristics. Such research is critical in addressing uncertainties in
estimating risk reductions likely to be achieved by alternative fine particle standards and
new implementation strategies.
(5) Uncertainties in the shape of concentration-response relationships, most specifically whether
linear or threshold models are more appropriate, significantly affects the confidence with
which risks and risk reductions can be estimated. Mechanistic and epidemiological research
highlighted above likely would help reduce such uncertainties.
A-3
-------
(6) Unaddressed confounders and methodological uncertainties inherent in epidemiological
studies of long-term PM exposures limit interpretations and conclusions that can be drawn
with regard to associations between PM and chronic health effects. Additional research and
analysis are needed to reduce the uncertainties related to the appropriate exposure periods
and historical air quality to consider in evaluating such studies and to better address life-
style and other potentially important cofactors.
(7) An important aspect in characterizing the nature of the mortality risk associated with short-
and long-term exposures to PM, from a public health perspective, is the extent to which
lifespans are being shortened. Available epidemiological evidence provides a very limited
basis for testing hypotheses as to whether and to what extent lifespans are shortened by only
a few days or by years. More research is needed to quantitatively characterize the degree of
prematurity of deaths associated with exposures to PM.
(8) The characterization of annual and daily background concentrations likely to occur across
the United States contains significant uncertainties. Additional air quality monitoring and
analyses that improve these background characterizations would help to reduce the
uncertainties in estimating health risks relevant to standard setting (i.e., those risks
associated with exposures to PM in excess of background levels).
(9) Despite long-standing staff recommendations for a comprehensive examination of the effects
associated with exposures to coarse-fraction particles, there continues to be a lack of animal,
clinical, and community studies in this area. Such research potentially would provide both
qualitative and quantitative information that could allow for the establishment of a coarse-
fraction particle standard rather than continued reliance on a PMJO standard as the means to
control exposures to coarse-fraction particles.
A-4
-------
Appendix B
U.S. Environmental Protection Agency
Particulate Matter Research Needs Workshop
B-l
-------
THE PARTICULATE MATTER RESEARCH NEEDS WORKSHOP
The EPA-sponsored PM Research Needs Workshop, held September 4 through 6, 1996,
in Research Triangle Park, NC, was attended by 45 EPA staff members and 50 non-EPA
representatives (attendees names and affiliations appear at the end of this appendix). Non-EPA
representatives, from the United States and abroad, represented academia, industry,
environmental organizations, other U.S. federal and state government agencies, and international
organizations and foreign governments. The workshop opened with introductory presentations
explaining the purpose and structure of the workshop. Then, in a series of parallel,
interdisciplinary breakout sessions, the participants discussed research needs under three broadly
defined areas: (1) epidemiology, (2) toxicology/dosimetry, and (3) exposure. To ensure a
desirable mix of interdisciplinary expertise, invited participants were assigned to one or another
breakout groups to discuss the following breakout topics.
Session 1. Epidemiology: PM exposure issues for epidemiology; Toxicology:
PM dosimetry (laboratory animal and human); and Exposure: atmospheric science,
sources, and modeling
Session 2. Epidemiology: health outcomes and sensitive populations; Toxicology:
PM composition; Exposure: background and personal exposure—Indoor/Outdoor
Session 3. Epidemiology: design and analysis; Toxicology: mechanisms of susceptibility
to PM; Exposure: measurement methods and networks
Almost every breakout group emphasized the need for continuing interdisciplinary
interaction to solve the many problems and questions identified during the discussion.
Planning Research Need—Expand the interdisciplinary discussion (involving
epidemiology, toxicology/dosimetry, and exposure) conducted at this workshop in
order to better define and prioritize the research needs and especially to identify
multidisciplinary approaches and programs to address the research needs.
Key points and recommendations emerging from the interdisciplinary discussions were
discussed during the final breakout sessions on epidemiology, toxicology/dosimetry, and
exposure. During these sessions, possible revisions to those sections of the draft EPA PM
research needs document were considered. Next, in plenary, rapporteurs reported on outcomes
from the prior breakout sessions, and participants discussed approaches and techniques for
B-2
-------
setting priorities for PM research. The plenary session was followed by breakout sessions during
which efforts were made to identify the most important questions, issues, and related research
needs and to determine their relative priority. The workshop concluded with concise summary
overviews of research strategies and plans of participating government and nongovernmental
organizations, followed by general discussion of research strategies, plans, and priorities.
As a result of the workshop discussions and written reviews provided by participants, some
new research needs were added and others modified or expanded. The workshop did not reach
final, overall consensus regarding prioritization, although much progress was made in identifying
top-priority questions, issues, and needs. However, subsequent to the workshop, EPA staff,
based on the workshop discussions and written reviews from participants, were able to articulate
10 high-priority questions, which provide a useful context for consideration of prioritization of
research needs. These questions are summarized in the prioritization chapter and presented in
full below.
PARTICULATE MATTER RESEARCH NEEDS: KEY QUESTIONS
The following key questions, not in order of priority, were developed by NCEA staff, based on
discussions at the September 1996 PM Research Needs Workshop and written review from
workshop participants.
(1) What steps can be taken to evaluate more definitively the strength (and weaknesses),
consistency, coherence, and shape of exposure-dose-response relationships between short-
term PM exposure parameters and various acute health outcomes? For example, would
acute PM-health effects associations, as evaluated by time-series analyses, be strengthened
(or possibly weakened) by
(a) using more precise and meaningful measurements of PM and other pollutant exposure
parameters (e.g., continuous measurements, cleaner separation of fine mode from
coarse PM, inclusion of ammonium nitrate and semivolatile organics, particle counts,
etc.)?
(b) using more sensitive and specific biological indicators of PM or of adverse health
effects (e.g., continuous measures of physiologic and immunologic function)?
B-3
-------
(c) using cohorts of sensitive subjects (e.g., panel studies of children, asthmatics,
cardiopulmonary patients)?
(d) using measurements and models to reduce error in estimated personal or community
exposure to ambient PM (e.g., using indoor/outdoor time patterns to better quantify
day-of-week and seasonal variations in concentration/exposure relationships, and
consideration of dose as a function of activity levels)?
(2) Can the amount of chronic morbidity and life shortening caused by long-term (chronic) PM
exposure be better quantified and applicable dose-response relationships elucidated by
(a) additional cross-sectional studies (e.g., with careful selection of cities that provide
necessary PM exposure contrasts, varying copollutant concentrations, and permit
corrections for other potential confounders)?
(b) using de novo cohorts or cohorts from other long-term health studies (e.g., coupling
retrospective or prospective PM exposure estimates to health information from other
ongoing health surveillance studies)?
(c) developing and using better techniques to quantify historical PM and copollutant
exposures or other historical experiences of study subjects (e.g., residential history,
indoor/outdoor time, and activity patterns, etc.)?
(3) Who is being affected, and what are important factors putting them at risk? What sensitive
subpopulations are most affected by short- and long-term PM exposures? Can critical host
risk factors be delineated, for example, with regard to
(a) health status (preexisting cardiovascular disease, acute respiratory infection, COPD,
asthma, etc.)?
(b) age (children and elderly)?
(c) genetic factors (predisposition to emphysema, deficient lung defense mechanisms,
cancer, etc.)?
(d) life style (smoking, nutrition, access to health care, activity patterns or levels, etc.)?
(e) differential respiratory tract dosimetry (regional deposition, retention), as influenced by
one or more of the above other factors?
(f) prior occupational or other nonambient PM exposures (hobbies, indoor cooking/
cleaning, etc.)?
B-4
-------
(4) What is the spectrum of acute and chronic health outcomes of PM exposure and by which
biological mechanisms do specific chemical components or size fractions of PM cause or
promote specific health effects?
(a) What are the acute effects of exposure to concentrated "real-world" (ambient) particles
in laboratory animal models of human disease? How can results of concentrated
particle exposures be extrapolated to equivalent human exposures and respiratory tract
doses? Concentrators in use now do not concentrate very small particles (< 0.1 um).
Are concentrators for ultrafine particles needed?
(b) Can in vivo and in vitro "screening" studies be used to compare and contrast effects of
exposure to real-world ambient particles from various geographic locations with
varying particle and copollutant mixes?
(c) What are differences in toxicity between particles produced in the laboratory, either
from pure chemicals or from ambient particles that have been collected, dried, and
resuspended ("laboratory" particles) and particles in ambient air or generated in smog
chambers that are in equilibrium with water vapor, gaseous pollutants and dissolved
components (in situ aerosol)?
(d) What are the relative toxicologic potencies of varying specific PM constituents by size
(ultrafine, fine, coarse) and chemical composition (transition metals, elemental carbon,
sulfate, nitrate, acidity, primary biological materials, organics, soil and other crustal
materials, etc.)?
(e) How does chronic PM exposure influence the pathogenesis and progression of chronic
cardiopulmonary diseases (chronic bronchitis, emphysema, asthma, chronic obstructive
lung disease and related cardiovascular complications, etc.)?
(f) What are the responses of susceptible human subpopulations to controlled exposure to
real-world PM, as well as to specific components?
(g) Can findings from in vitro and instillation studies be confirmed by inhalation exposure
in healthy laboratory animals and humans and in laboratory animal models of human
disease?
B-5
-------
(h) How do age, sex, and other potential host modifying factors influence human and
animal model responses to exposures to concentrated real-world particles and specific
PM subcomponents (as listed above)?
(i) Can epidemiologic and biostatistical methods further differentiate the effects of
individual PM components or of specific sources of PM from the entire ambient PM
complex or the entire air pollution complex (including gases and particles)?
(j) What are potential mechanisms by which particle-induced effects could occur outside
the respiratory tract? For example, cardiac, vascular, and hematologic responses;
immunological responses; neurological responses; and release of various blood-borne
mediators.
(5) How can dosimetry models be improved to contribute to evaluation of findings in
epidemiology, controlled human exposure studies, and laboratory animal studies and to
improve insight on potential mechanisms of action? What data are needed to enhance the
ability of dosimetry models to describe various factors, including both physicochemical
attributes of ambient PM as well as host factors, that influence inhaled dose, clearance,
retention, and response? What data are required to construct the different internal dose
metrics that may correspond to various plausible mechanisms of action? Can the variability
in different dose metrics, both within humans and across species, be better characterized?
(a) What is the relationship between exposure, inhalability, and internally deposited
regional dose for PM aerosols of different sizes (ultrafine to coarse), distributions
(monodisperse and polydisperse), and composition (hygroscopicity, density, and
shape)? Especially needed are data for persons with respiratory disease and more
information on ultrafine particles.
(b) What is the relationship between exposure, inhalability, and internally deposited
regional dose for different PM aerosols (as described in item A above) across age
(children, adults, and the elderly), sex, and health status (e.g., preexisting
cardiovascular disease, asthma, COPD) in humans and across species tested in
bioassays? How do these relationships depend on differences in anatomic dimensions
(e.g., airway length, diameter, number) and airflow (ventilation patterns) across these
same categories?
B-6
-------
(c) What particle factors govern clearance and retention? How do particle size and
composition influence dissolution rates, mucociliary transport, macrophage/epithelial
cell endocytosis rates, and bioavailability?
(d) What are the clearance processes and rates for different PM aerosols (as described in
item A above) across age (children, adults, and the elderly), sex, and health status (e.g.,
preexisting cardiovascular disease, asthma, COPD) in humans and across species?
(e) What are the mechanisms and rates of repair for the tissues and cells of the different
respiratory tract regions across age, sex, and health status in humans and across
species?
(f) Do host factors such as age, sex, and health status influence the number or types of
target cells and their relationship to toxicity and detoxification of PM?
(g) How can laboratory animal models be further developed or refined to serve as analogs
of the human population at risk in terms of host factors and mechanisms of action?
(6) What are characteristics of ambient particulate matter in different U.S. regions in terms of
(a) chemical composition (transition metals; sulfate, nitrate, hydrogen, and ammonium
ions; elemental and organic carbon; water; and crustal and trace elements)?
(b) size distribution (almost no data on ultrafines in cities)?
(c) variability (spatial variation across a given city on a daily basis and from city to city on
a regional basis; temporal variability over diurnal cycles, day-to-day, and seasonally,
yearly)?
(d) sources (both natural and anthropogenic)?
(e) development and deployment of improved methods, by which poorly understood
specific PM components can be better characterized, for example
- in situ aerosol versus laboratory particles? Particles dispersed in ambient air and in
equilibrium with water vapor and gaseous pollutants (in situ aerosol) differ from
particles collected on filters and dried (laboratory particles). The structure of in situ
aerosol particles need to be investigated in terms of the insoluble core; the
biologically, chemically, and photochemically reactive species dissolved in the
aqueous layer; and the outer skin.
B-7
-------
- primary biological aerosol particles (PBAP)? PBAP are airborne particles (dead or
alive) that are or were derived from living organisms, including microorganisms and
fragments of living things (e.g., bacteria, viruses, pollen, mold spores, fragments of
insects and plants).
- organic compounds, both nonvolatile and semivolatile?
- ammonium nitrate? Most measurement techniques for PM mass lose a significant
fraction of ammonium nitrate. Therefore, more reliable measurement techniques are
needed to determine the concentrations and the spatial and temporal variability of
ammonium nitrate.
(f) dissolution rate in body fluids and bioavailability by size and composition?
(7) What is the relationship between ambient PM concentration and personal exposure to PM?
(a) What are the concentrations and health effects of the "personal cloud" (PM associated
with presence and activity of a person) and of PM generated in various
microenvironments (homes, cars, offices, hospitals, etc)?
(b) How do the composition, concentration and health effects of these types of PM differ
from those of PM of ambient origin?
(c) What is the relationship between total personal exposure and personal exposure to PM
of ambient origin?
(d) What is the relationship between ambient PM concentrations outdoors (as measured by
central monitors) and concentrations of ambient PM indoors?
(e) What is the relationship between host characteristics (health status, age, and life style)
and exposure to ambient and personal PM?
(8) How can a standardized, cost-effective, widespread, research-grade ambient PM monitoring
network best be achieved to provide improved air quality data for PM exposure and
epidemiologic studies?
(a) Augmentation of existing local compliance monitoring networks in selected cities?
(b) De novo establishment of a research-grade national ambient monitoring network?
(c) Use of expanded measurements of specific physical and chemical parameters and
appropriate sampling frequency to better reflect continuous, daily, and seasonal
variations in PM?
B-8
-------
(9) Can the spatial and temporal variability in exposure be better characterized by
(a) developing and validating improved air quality models to relate emissions to ambient
concentrations of PM components?
(b) developing a better understanding of the factors that relate personal and community
exposure to concentrations measured at a central site?
(c) developing techniques to characterize changes in the aerosol size distribution and
composition from sources to receptor sites?
(d) developing and validating improved apportionment models to describe PM in terms of
contributions of a specific source or source categories?
(10) Can the nonanthropogenic background and other noncontrollable background concentrations
to be used in risk assessments be estimated by
(a) large-scale chemistry and transport models, using emission inventories for biological
sources and sources outside the area of concern?
(b) measurements, using multilevel trajectory models or other meteorological tools to
identify periods when measurement sites are dominated by background contributions?
B-9
-------
REGISTRANTS AT THE PARTICULATE MATTER RESEARCH NEEDS
WORKSHOP
Non-EPA Attendees
Paula Anderson
Pulmonary and Critical Care Medicine
University of Arkansas Medical School
Little Rock, AR
James Ball
Science Research Lab
Ford Motor Company
Dearborn, MI
William Bennett
Center for Environmental Medicine
and Lung Biology
University of North Carolina
Chapel Hill, NC
Henk Bloemen
RIVM
Bilthoven, The Netherlands
Philippe Bourdeau, Director
Directorate General for Scientific
Research and Development ULB,
Brussels, Belgium
William Bunn
Navistar International Engine Manu. Assoc.
Chicago, IL
Richard Burnett
Environmental Health Center
Health and Welfare Canada
Ottawa, Ontario, Canada
Steven Cadle
GM Research and Development Center
Warren, MI
Bingheng Chen
Assessment of Risk and Methodologies
International Programme on Chemical
Safety
World Health Organization
Geneva, Switzerland
Noreen Clancy
NAPAP
Washington, DC
Aaron Cohen
Health Effects Institute
Cambridge, MA
Steve Colome
Irvine, CA
John Core
WESTAR Council
Portland, OR
Maria Costantini
Health Effects Institute
Cambridge, MA
Robert Drew
American Petroleum Institute
Washington, DC
Kevin Driscoll
Procter and Gamble
Cincinnati, OH
Sylvia Edgerton
U.S. Department of Energy
Germantown, MD
B-10
-------
Lynne Edwards
European Commission
Brussels, Belgium
Mark Frampton
Pulmonary Disease
University of Rochester Medical Center
Rochester, NY
Sheldon Friedlander
UCLA
Department of Chemical Engineering
Los Angeles, CA
Ian Gilmour
Durham, NC
Helger Hauck
Institute Umwelthygiene,
Vienna, Austria
John Holmes
State of California
Air Resources Board
Sacramento, CA
Ruprecht Jaenicke
Institute for Physics of the
Atmosphere
University Mainz, Germany
Michael Kleinman
Department of Community and
Environmental Medicine
University of California-Irvine
Irvine, CA
Brian Leaderer
John B. Pierce Lab
New Haven, CT
Eric Lebret
RIVM
Bilthoven, The Netherlands
Benjamin Liu
Department of Mechanical Engineering
Institute of Technology
University of Minnesota
Minneapolis, MN
George Malindzak
NIEHS
Research Triangle Park, NC
David Mannino
CDC
Air Pollution Branch
Atlanta, GA
Roger McClellan
President, CUT
Research Triangle Park, NC
Fred Miller
CUT
Research Triangle Park, NC
Suresh Moolgavkar
Fred Hutchinson Cancer
Research Center
Seattle, WA
Lucas Neas
Harvard School of Public Health
Boston, MA
Karin Ann Pacheco
National Jewish Center for Immunology
and Respiratory Medicine
Denver, CO
B-ll
-------
Joyce Penner
Atmospheric Oceanic Space Sciences
Ann Arbor, MI
Kent Pinkerton
Department of Anatomy, Physiology,
and Cell Biology
University of California, Davis
Davis, CA
Roy Richards
School of Molecular and Medical
Biosciences
University of Wales College of Cardiff
Cardiff, United Kingdom
Peter Rombout
Department for Inhalation Toxicology
RIVM
Bilthoven, The Netherlands
Ragnar Rylander
Department of Environmental Medicine
University of Gothenburg
Goteborg, Sweden
K.C. Shaw
Geneva Steel
Provo, UT
Quinlan Shea
National Mining Association
Washington, DC
Deborah Shprentz
Natural Resources Defense Council
Washington, DC
Carl M. Shy
Department of Epidemiology
School of Public Health
University of North Carolina
Chapel Hill, NC
Burt Snipes
Inhalation Toxicology Research Institute
Lovelace Biomedical and Environmental
Research Institute, Inc.
Albuquerque, NM
Robert Statnick
National Mining Association
Pittsburgh, PA
Ira Tager
University of California-Berkeley
Berkeley, CA
George Thurston
Institute of Environmental Medicine
New York University Medical Center
Tuxedo, NY
Richard Turco
Department of Atmospheric Sciences
UCLA
Los Angeles, CA
Barbara Turpin
Rutgers University
Environmental Sciences
New Brunswick, NJ
Michael Uhart
NAPAP
Washington, DC
Jaroslav J. Vostal
EHACInt.
Bloomfield Hills, MI
Ron White
American Lung Association
Washington, DC
Ronald Wyzga
Electric Power Research Institute
Palo Alto, CA
B-12
-------
EPA Attendees
John Bachmann
OAQPS
Research Triangle Park, NC
Susanne Becker
NHEERL-RTP
Research Triangle Park, NC
Frank Binkowski
NERL-RTP
Research Triangle Park, NC
Jane Caldwell
OAQPS
Research Triangle Park, NC
Robert Chapman
NCEA-RTP
Research Triangle Park, NC
Jason Ching
NERL-RTP
Research Triangle Park, NC
Beverly Comfort
NCEA-RTP
Research Triangle Park, NC
Dan Costa
NHEERL-RTP
Research Triangle Park, NC
Kevin Dreher
NHEERL-RTP
Research Triangle Park, NC
Ed Edney
NERL-RTP
Research Triangle Park, NC
William Ewald
NCEA-RTP
Research Triangle Park, NC
Bob Fegley
ORSI
Washington, DC
Larry Folinsbee
NCEA-RTP
Research Triangle Park, NC
Neil Frank
OAQPS
Research Triangle Park, NC
Stephen Gavett
NHEERL-RTP
Research Triangle Park, NC
Andrew Ohio
NHEERL-RTP
Research Triangle Park, NC
Judy Graham
NERL-RTP
Research Triangle Park, NC
Les Grant
NCEA-RTP
Research Triangle Park, NC
John Haines
OAQPS
Research Triangle Park, NC
Gary Hatch
NHEERL-RTP
Research Triangle Park, NC
B-13
-------
Annie Jarabek
NCEA-RTP
Research Triangle Park, NC
Chong Kim
NHEERL-RTP
Research Triangle Park, NC
Trish Koman
OAQPS
Research Triangle Park, NC
Dennis Kotchmar
NCEA-RTP
Research Triangle Park, NC
Joellen Lewtas
NHEERL-RTP
Research Triangle Park, NC
Dave Mage
NERL-RTP
Research Triangle Park, NC
Allan Marcus
NCEA-RTP
Research Triangle Park, NC
Frank McElroy
NERL-RTP
Research Triangle Park, NC
David McKee
OAQPS
Research Triangle Park, NC
Doug McKinney
NRMRL-RTP
Research Triangle Park, NC
Caroline Miller
OAQPS
Research Triangle Park, NC
Deran Pashayan
ESRD-DC
Washington, DC
Gerain Perry
ORMA
Washington, DC
Joe Pinto
NCEA-RTP
Research Triangle Park, NC
Larry Purdue
NERL-RTP
Research Triangle Park, NC
Harvey Richmond
OAQPS
Research Triangle Park, NC
Mary Jane Selgrade
NHEERL-RTP
Research Triangle Park, NC
Chon Shoaf
NCEA-RTP
Research Triangle Park, NC
Robert Stevens
NERL-RTP
Research Triangle Park, NC
Susan Stone
OAQPS
Research Triangle Park, NC
Kevin Teichman
OSPRI
Washington, DC
Gene Tucker
NRMRL-RTP
Research Triangle Park, NC
B-14
-------
John Vandenberg William Wilson
NHEERL-RTP NCEA-RTP
Research Triangle Park, NC Research Triangle Park, NC
Jim Vickery Roy Zweidinger
NERL-RTP NERL-RTP
Research Triangle Park, NC Research Triangle Park, NC
Russ Wiener
NERL-RTP
Research Triangle Park, NC
B-15
-------
Appendix C
U.S. Environmental Protection Agency
Science Advisory Board
Clean Air Scientific Advisory Committee
Panel for Review of Particulate Matter Research Needs
for Health Risk Assessment
September 1996
C-l
-------
Members
Dr. Joe L. Mauderly (Acting Chair)
Inhalation Toxicology Research Institute
Lovelace Biomedical and Environmental
Research Institute
Albuquerque, NM
Dr. George T. Wolff (Immediate Post Chair)
Environmental and Energy Staff
General Motors
Detroit, MI
Dr. Stephen M. Ayres
Virginia Commonwealth University
Medical College of Virgina
Richmond, VA
Dr. Phil Hopke
Clarkson University
Pottsdam, NY
Consultants
Dr. Jay S. Jacobson
Boyce Thompson Institute
Cornell .University
Ithaca, NY
Dr. James H. Price, Jr.
Texas Natural Resource Conservation
Commission
Austin, TX
Dr. Warren White
Washington University
St. Louis, MO
Dr. Petros Koutrakis
Harvard School of Public Health
Boston, MA
Dr. Kinley Larntz
University of Minnesota
St. Paul, MN
Dr. Timonthy Larson
Environmental Science and
Environmental Program
St. Paul, MN
Dr. Allan Legge
Biosphere Solutions
Calgary, Alberta, Canada
Dr. Morton Lippman
Institute of Environmental Medicine
New York University
Tuxedo, NY
Dr. Roger O. McClellan
Chemical Industry Institute of Toxicology
Research Triangle Park, NC
Dr. Daniel Menzel
University of California, Irvine
Department of Community and
Environmental Medicine
Irvine, CA
Dr. Paulette Middleton
Science and Policy Associates
Boulder, CO
C-2
-------
Dr. William R. Pierson
Desert Research Institute
Energy and Environmental Engineering
Center
Reno, NV
Dr. Jonathan Samet
Johns Hopkins University
School of Hygiene and Public Health
Department of Epidemiology
Baltimore, MD
Dr. Christian Seigneur
Atmospheric and Environmental
Research, Inc.
San Ramon, CA
Dr. Carl M. Shy
University of North Carolina
Department of Epidemiology
School of Public Health
Chapel Hill, NC
Dr. Frank Speizer
Harvard Medical School
Channing Laboratory
Boston, MA
Dr. Jan Stolwijk
Yale University
Epidemiology and Public Health
New Haven, CT
Dr. Mark Utell
University of Rochester Medical Center
Pulmonary Disease Unit
Rochester, NY
C-3
-------
Appendix D
Clean Air Scientific Advisory Committee Evaluation
of Research Needs for the Particulate Matter
National Ambient Air Quality Standards
D-l
-------
NOTICE
This report has been written as a part of the activities of the Science Advisory Board,
a public advisory group providing extramural scientific information and advice to the
Administrator and other officials of the Environmental Protection Agency. The Board is
structured to provide balanced expert assessment of scientific matters related to problems faced
by the Agency. This report has not been reviewed for approval by the Agency; and hence, the
contents of this report do not necessarily represent the views and policies of the Environmental
Protection Agency or other agencies in the Federal government. Mention of trade names or
commercial products does not constitute a recommendation for use.
D-2
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
March 12, 1997
OFFICE OF THE ADMINISTRATOR
SCIENCE ADVISORY BOARD
EPA-SAB-CASAC-LTR-97-004
Honorable Carol M. Browner
Administrator
U.S. Environmental Protection Agency
401 M Street SW
Washington, DC 20460
Subject: Evaluation of Research Needs for the Particulate Matter National Ambient Air
Quality Standards (NAAQS)
Dear Ms. Browner:
The Clean Air Scientific Advisory Committee (CAS AC) of EPA's Science Advisory
Board (SAB), supplemented by a number of expert consultants (together referred to as the
"Panel"), reviewed the two draft documents, Particulate Matter Research Needs for Human
Health Risk Assessment (EPA, 1996a) and Particulate Matter Research Program Strategy (EPA,
1996b) at a public meeting in Chapel Hill, NC on November 18 and 19, 1996. At that meeting
and in subsequent written comments that were provided to EPA staff (hereafter referred to as the
"Staff), the Panel made numerous recommendations for improving the documents. This letter is
a summary of the Panel's key comments and conclusions. Staff is referred to the transcript of the
meeting and to individual members' comments for details and issues beyond this summary.
The Panel commends the Staff for developing these important documents, and notes that
the review drafts represent significant steps toward setting the stage for the research that is
critical to resolving present uncertainties about the health impacts of paniculate matter (PM).
In its past reviews of the Particulate Matter Criteria Document and Staff Paper, the Panel
repeatedly asserted its strong recommendation that critical PM research be identified and a
strategy for its accomplishment be developed. With revision, these documents will set forth a
framework from which more detailed plans can be developed by EPA and other stakeholder
organizations.
D-3
-------
1. Particulate Matter Research Needs for Human Health Risk Assessment
The document is of sufficient length and complexity that it would benefit from addition
of an Executive Summary and a final section in which Staff presents its summary and
conclusions, as well as reorganization to give greater recognition to phased needs and goals.
The comprehensiveness of this document is both a strength and weakness. In its present
form, it is an encyclopedic compilation of PM research needs. The document's utility suffers
from its failure to clearly place PM research needs in the context of the present large
uncertainties in assessing the health risks from inhaled PM, and thus in setting the form and level
of PM NAAQS. Beginning with a risk assessment framework would resolve many of the
specific criticisms raised in individual Panel members' comments. A useful approach would be
to begin with a framework consisting of the key steps in health risk assessment and standard
setting. The key uncertainties presently limiting accomplishment of each step could then be
listed in summary form and then summary statements of the information needed to reduce the
key uncertainties could be listed. With this structure as a prologue, the most important research
and the research approaches likely to be most productive could be described. This risk-based
framework should look forward to the next review of the PM NAAQS; however, a commitment
to research over a longer period (e.g., 10-15 years) is also needed. The likelihood of having a
significant impact on the regulatory decision in 2002 is a useful criterion for prioritizing much of
the proposed research. The document would be much improved by summarizing the above
information in tabular or figure form.
Critical to the above process is an accurate portrayal of the nature and magnitude of
present uncertainties. Several Panel members expressed concern that the present draft does not
reflect present uncertainties accurately. The Panel noted that the present draft conveys the notion
that the direct causality of PM, and especially PM2 5, in the health effects observed by
epidemiology is established. While the Panel agrees that present evidence warrants concern and
most members support implementation of a fine particle standard, the Panel urges that it be
explicitly stated that the causality of PM2 5 has not been clearly established. In this and previous
meetings, the Panel has noted a range of important uncertainties. For example, in its CAS AC
noted uncertainties concerning the relationship between area monitoring data and personal
exposure, and concerning the suitability of PM2 5 as the best surrogate for the causative agents(s).
CAS AC also noted that some reviews of the epidemiological database indicated that the health
effects could not be unambiguously associated with PM. In its June 13,1996 letter addressing
the PM Staff Paper (SAB, 1996b), CASAC offered a range of views about the justification for,
and most appropriate level of, a PM2 5 standard, and listed numerous specific uncertainties that
need to be resolved.
This review of research needs requires greater consideration of the magnitude of funding
required to fill the most critical information gaps. Much of the proposed research is feasible, but
cannot be conducted within the level of funding directed toward PM research in the present or
recent fiscal years. The continued failure to fund PM research at a level commensurate with its
importance is a critical gap in EPA's research strategy. The document does not portray the cost
D-4
-------
of research costs and time lines would place PM research needs in a budget context and could
facilitate discussion of sharing of costs among agencies and other sponsors.
The review of research needs would also benefit from more consideration of the technical
practicality and time requirements of conducting the proposed research. As noted in individual
members' comments, some of the research suggested is not presently feasible for technological
reasons. The time required to fill critical information gaps is not portrayed. The document
would benefit from the placement of research in a time context with the next review of the
PM NAAQS as a focal point. Although work on many issues must continue beyond that point,
this benchmark would engender a realistic expectation of the work that could be accomplished by
then, and as noted earlier, would heal with prioritization.
There should be greater emphasis on resolving uncertainties about the long-term effects
of PM. Additional attention should be focused on long-term effects, such as life shortening or
progressive disease. Accompanying data are needed on long-term PM levels, trends, and
characteristics, as well as levels of other pollutants. The Panel felt that there was little need for
documenting additional examples of associations between short-term increases in PM and health
effects using the same approaches as in the past. There is a need for new data sets providing
improved understandings of the individuals incurring short-term effects and the physical-
chemical nature of the PM to which there were exposed, and for alternate data analysis
techniques.
The Panel noted a lack of emphasis on retrospective research to determine the
effectiveness with which reductions in PM and other pollutants reduce adverse health effects.
Many of the data cited as demonstrating the health effects of current concern were collected
10-15 years ago. The downward trend in ambient PM should provide opportunities to
demonstrate an associated health benefit, and it might also be possible to follow implementation
of specific source controls in some locations with studies to detect improvements in health
indices thought to be associated with PM. The Panel appreciated the difficulty, pointed out by
Staff, of detecting reductions in risk associated with reductions of PM in view of their probable
small magnitude and numerous confounding factors. The Panel, however, would also remind the
Agency that it is precisely these health risks in the presence of confounding influences and other
uncertainties that give rise to the proposed change in the PM standard. Demonstration of an
association between reductions of PM and adverse health outcomes would support causality.
The need for cross-disciplinary and international interactions is not adequately
emphasized. The efforts of atmospheric scientists, laboratory researchers, clinical researchers,
and epidemiologists will be required to resolve several of the uncertainties, and consideration
should be given to providing a framework for integrating these efforts. There should be mention
of the need for research training with a focus on cross-disciplinary perspectives and
collaborations. Collaboration of EPA and its supported researchers in international efforts, for
example with the "Air Pollution and Health: European Project", should also be emphasized.
In his October 28, 1996 letter (EPA, 1996c), Dr. Lester Grant charged the Panel with
providing feedback on three issues (identified as a), b), and c) below). In aggregate, the above
D-5
-------
comments and the comments of individual Panel members, submitted to Staff, address those
issues. We provide the additional following comments.
a) Are the key questions/issues identified as needing to be addressed on the mark? Has too
much or too little emphasis been placed on one or another of the key questions? Do other
key questions/issues need to be added?
(1) Several Panel members noted that the section containing key questions could be
improved by stating the key questions in summary form and eliminating, or
summarizing more succinctly, the "subquestions".
(2) Less emphasis should be given to short-term epidemiology and greater emphasis
should be given to long-term epidemiology and associated exposure characterization.
(3) In question 4.C and elsewhere, eliminate the "live" and "dead" particle terminology.1
(4) Question 8 is framed more as an operational issue than a research need. It is
probably best stated as a subquestion under questions 7 and 9.
b) Are the research needs identified subsequently in the document appropriate and
adequately characterized? Are there others that need to be added?
There was no consensus that major research needs were overlooked. Some members
noted the need for an improved understanding of PM concentrations that might be
considered "background", or representative of broader rural and semirural areas than
present monitoring sites allow. The individual comments contain numerous additional
suggestions for improving the scope and description of the needs. Although few of the
comments of individuals were mutually exclusive, their diverse nature makes it
impractical to summarize them in this letter.
c) Can the Committee assist EPA in terms of helping to prioritize the stated research needs?
Within given categories (e.g., exposure, health, etc.) and/or across categories?
An exhaustive prioritization of the needs listed in this document was not undertaken by
the Panel; priorities were addressed in greater detail in review of the Research Strategy
document. While Staff is encouraged to consider comments of individual Panel members
on priorities within different research topics, the following topics were generally
considered to be of high priority:
1 "Dead" particles are either laboratory particles or collected, dried and resuspended ambient PM. "Live" particles
are ambient air or generated in smog chambers that are in equilibrium with water vapor, gaseous pollutants and
dissolved components. (Editors note: "live" has been replaced by suspended or in situ and "dead" by dried in the
research needs document.
D-6
-------
(1) Effects of long-term exposures and relative contributions of short-term spikes and
cumulative exposures to long-term health outcomes.
(2) Mechanisms by which PM could contribute to life shortening, daily mortality and
morbidity.
(3) Linkages between PM data from area monitors and personal exposures
(4) PM classes and physical-chemical characteristics associated with different health
effects, and
(5) extent to which PM causes health effects independently of other pollutants.
2. Particulate Matter Research Program Strategy
a) Review and comment on the research questions and issues EPA has selected to focus on
and the approached EPA is planning to use to address those questions/issues.
b) Comments and recommendations regarding relative priorities for the various stated
research areas/directions.
The following comments address these and other issues in areas for which opinion could
be generalized. Staff is encouraged to review the wide range of additional comments contained
in the written comments of individual Panel members, which have been submitted to Staff.
This document is presented as a statement of EPA strategy for PM research, but it failed
short of defining and defending a strategic action plan. Like the Research Needs document, this
draft does not provide an adequate risk assessment framework for identifying and prioritizing
research and for allocating resources to the effort. The strategy should flow from the Research
Needs document by beginning with an expression of key research needs arising from present
uncertainties in setting the PM NAAQS, and should be targeted toward improving the Agency's
position at the next review. This structure would help resolve the inadequate explanation in the
present draft of the basis for ranking. It is not clear which group, or by what process, the present
ranking and strategy were developed. The present draft does not place its strategy in the context
of research under way or proposed in other offices within the Agency, in other Agencies and
organizations, or in other countries. It is not clear, for example, if this is an Agency-wide
strategy or just a strategy for ORD.
The critical issues of the allocation of resources to PM research and the progress likely to
result from those expenditures are missing from the discussion of strategy. Oral presentations by
Staff indicated that a total of $20 million annually was projected for EPA PM research, and that
represents approximately 0.3% of EPA's budget. Moreover, it appears that only approximately
5% of EPA's research staff is focused on PM issues. The Panel was unanimous in expressing its
strong concern that this level of funding and staffing falls far short of the resources needed to
make progress commensurate with the health and economic implications of estimated PM effects
D-7
-------
and costs of controls. At this rate, support over even the five-year period between PM NAAQS
reviews would fall below annual expenditures by EPA and other Agencies in issues having lesser
estimated health and economic impacts. As a related issue, EPA needs to highlight linkages to
other programs within the Agency and to efforts in other agencies that, in aggregate, constitute
the nation's effort to understand PM and its effects.
This document shares with the Research Needs document the characteristic of overstating
the certainty of the causality of PM in the health effects observed by epidemiology, and
especially the level of certainty concerning the causality of PM2 5 in the adverse effects. Indeed,
because the magnitude of this uncertainty underlies and supports the priority of many of the
strategic research goals, the uncertainty should be emphasized rather than minimized.
Because the human health research priorities should flow from the information needs
described in the Research Needs document, health effects issues that are not listed in that
document should not be raised anew in this one. Examples of new issues, such as the mention of
altitude as a variable of concern, are contained in individual Panel members' comments.
The key questions beginning on page 14 should be portrayed more clearly. They should
be organized around the framework of risk assessment, should be stated more succinctly, and
should be followed by a succinct statement of the basis for their importance. If they are to be
retained, the subheadings under each key question should be prioritized.
Several Panel members commented that the structure of the ranking criteria beginning on
page 19 was not sufficiently focused. An example of a more focused approach might be:
a) likely impact on reducing uncertainties key to consideration of the PM NAAQS; b) probability
of success within technology and resources available; and c) likelihood of creating knowledge
also useful in other areas.
The core issue of the document is the prioritization of research topics. As might be
expected from a Panel consisting largely of senior researchers from different disciplines, a range
of diverse and sometimes conflicting opinions was offered regarding research priorities. This
summary does not attempt to portray fully this range of opinion; Staff is encouraged to examine
the written comments of individual Panel members.
There was consensus that epidemiological research on links between long-term exposure
to PM and life shortening and other long-term health effects was among the highest priorities.
Research on short-term effects should focus on refining our understanding of exposure-dose-
effects relationships. Priority should be given to epidemiological studies of either type which
provide the ability to examine linkages between health effects and personal exposures to
physical-chemical subclasses of PM. When known, the nature and dose-response relationship of
the effects of individual compounds in pure form might provide a point of reference useful for
judging the plausibility of effects estimated for those compounds encountered as constituents of
PM.
D-8
-------
There was also consensus that laboratory and clinical research exploring potential
mechanisms of response to PM was among the highest priorities. Greatest value was placed on
research exploring associations between physical-chemical PM characteristics and response
pathways and potency. High value was also placed on studies exploring the existence and nature
of responses at environmentally-relevant doses of PM.
Research providing a better understanding of personal exposure, and especially of
individuals thought to be most susceptible, was given high priority.
Beyond the above priorities, opinion was mixed and defied straightforward summary.
There was mixed enthusiasm for atmospheric modeling and characterization of source emissions.
Studies of the dosimetry of inhaled particles in normal subjects was not given strong support,
although it was agreed that present dosimetry models could benefit from a better understanding
of particle deposition and clearance in abnormal lungs. There were mixed views regarding the
priority of developing tools for market-based control approaches. Some members favored
conducting research to improve market-based approaches. Others warned that not all PM2 5
species are equipotent and that such approaches must be informed by an understanding of the
relative contributions of different physical-chemical classes of PM within size ranges. Staff is
advised to weigh these issues in view of individual members' comments.
3. Summary
The Panel commends Staff for initiating the strategic planning which resulted in these
draft documents, and encourages Staff to undertake the revisions necessary for the documents to
serve as a solid foundation for EPA's PM research program. These documents can play a critical
role in EPA's ability to fulfill its mission to protect the public health from airborne pollutants.
The Panel recognized that some of the recommended changes will require significant effort and
additional resources, but believes that the effort will be well-placed in improving EPA's PM
research program and the benefits attributable to the program's findings. In view of the
importance that Panel attached to the PM research program and thus the proposed revisions, the
Panel looks forward to the opportunity to review the revised documents. The Panel appreciated
the opportunity to provide comments on these documents, and looks forward to completion of
this important effort. We look forward to your response to our advice.
Sincerely,
Dr. Joseph L. Mauderly, Chair
Clean Air Scientific Advisory Committee
Dr. George T. Wolff, Immediate Past Chair
Clean Air Scientific Advisory Committee
D-9
-------
References Cited
EPA. 1996a. Particulate Matter Research Needs for Human Health Risk Assessment. External
Review Draft. NCEA-R-0973. U.S. Environmental Protection Agency, National Center
for Environmental Assessment (NCEA), Office of Research and Development, Research
Triangle Park, NC. October 25, 1996.
EPA. 1996b. Particulate Matter Research Program Strategy, External Review Draft. NHEERL
MS-97-019. U.S. Environmental Protection Agency, office of Research and
Development, Research Triangle Park, NC October 1996.
EPA. 1996c. Letter transmitting review materials and the charge to CASAC from Dr. Lester
Grant, Director, NCEA, to Dr. George Wolff, Chair, CASAC. October 28, 1996.
SAB. 1996a. Closure by the Clean Air Scientific Advisory Committee (CASAC) on the draft
, . Air Quality Criteria for Particulate Matter. Clean Air Scientific Advisory Committee,
Science Advisory Board, U.S. Environmental Protection Agency, Washington, DC.
EPA-SAB-CASAC-LTR-96-005. March 15, 1996.
SAB. 1996b. Closure by the Clean Air Scientific Advisory Committee (CASAC) on the Staff
Paper for Particulate Matter. Clean Air Scientific Advisory Committee, Science
Advisory Board, U.S. Environmental Protection Agency, Washington, DC.
EPA-SAB-CASAC-LTR-96-008. June 13, 1996.
D-10
-------
|