United States
Environmental Protection
Agency
Office of the Administrator
Science Advisory Board
Washington DC 20460
SAB-EC-88-040B
September 1988
Final Report
Appendix B:
Strategies for Exposure
Assessment Research
Report of the Exposure
Assessment Subcommittee
Research Strategies Committee
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NOTICE
This report has b = rŧn 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 a balanced, expert assessment
of scientific matters related to problems facing the Agency.
This report has not been reviewed for approval by the Agency;
hence, the contents of this report do not necessarily
represent the views and policies of the Environmental Protection
Agency or of other Federal agencies. Any mention of trade
names or commercial products do not constitute endorsement or
recommendation for use.
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TABLE OF CONTENTS
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1.1 Overview
1.2 Recommendations
n TNTPODUCTTON . ; ... ...
2 . 1 Overview and Examples
2.2 Definition of Exposure
2 . 3 Goal Statement
2.4 Categories of Exposure Determinations
and their Limitations
0 RATIONALE FOR EXPOSURE ASSESSMENT
0 APPROACHES TO HUMAN EXPOSURE ASSESSMENT ....
4 . 1 Overview
4.2 Methodologies
4.2.1 Personal Monitoring
4.2.2 Modeling
4.2.3 Biomarkers
4.3 Intermedia Concerns
0 ELEMENTS OF EXPOSURE .
5 . 1 Overview
5 . 2 Components
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5.2.1 Selection of Representative Samples
5.2.2 Defining Sample Sizes
5.2.3 Sampling, Monitoring Methods, and
Averaging Times
5.2.4 Time-Activity Patterns
. 0 EXAMPLES OF EXPOSURE ASSESSMENT RESEARCH NEEDS .
6 . 1 Exposure Assessment - General
6.2 Acidic Aerosols and Gases
6.3 Exposures to Biological Aerosols
6 . 4 Environmental Tobacco Smoke
6.5 Pesticides
6.6 Volatile Organic Compounds
6.7 Time Activity Patterns and Behavior Factors
. 0 BIOMARKERS OF EXPOSURE
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9.0
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. 1 Assessing Environmental Exposure
8.1.1 Interfaces
8.1.2 Account ab i 1 i ty
8.1.3 Long Term Commitment
8.1.4 Other Federal Research
8.1.5 Educational Training
.2 Exposure Assessment Planning
8.2.1 Research in Exposure Assessment
8.2.2 Coordination and Technical Support
8.2.3 Development of Agency-wide Program
8.2.4 Outreach
MONITORING AND RISK ASSESSMENT
. 1 Importance
.2 Tools
. 3 What Can be Done Now
. 4 Research Needs
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U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
RESEARCH STRATEGIES COMMITTEE
Exposure Assessment Subcommittee
Chairman
Dr. Bernard Goldstein, Chairman, Department of Environmental and
Community Medicine, UMDNJ-Robert Wood Johnson Medical
School, Piscataway, New Jersey *
Members
Dr. Rolf Hartung, School of Public Health, University of
Michigan, Ann Arbor, Michigan
Dr. Brian Leaderer, Pierce Laboratory, Yale University, New
Haven, Connecticut
Dr. Morton Lippmann, Institute of Environmental Medicine, New
York University, Tuxedo, New York
Dr. Donald O'Connor, Civil Engineering, Manhattan College,
Mahwah, New Jersey
Dr. Jack Spengler, Harvard University, Boston, Massachusetts
Invited EPA Participants
Dr. Michael Callahan, Exposure Assessment Group, Office of
Research and Development, U.S. EPA, Washington, DC
Dr. Wayne Ott, Air and Toxic Radiations Monitoring Research
Staff, Office of Research and Development, U.S. EPA,
Washington, DC
Science Advisory Board Staff
Mr. A. Robert Flaak, Environmental Scientist and Executive
Secretary, Science Advisory Board (A-101F), U.S.
Environmental Protection Agency, Washington, DC 20460
Ms. Carolyn Osborne, Staff Secretary, Science Advisory Board
(A-101F), U.S. Environmental Protection Agency, Washington,
DC 20460
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1.0 EXECUTIVE SUMMARY
1.l Overview
Reducing uncertainty in environmental risk assessments is a major
problem facing the U.S. Environmental Protection Agency (EPA). A
critical factor in understanding those risks is the amount of
available information concerning the number of people exposed to
environmental pollutants and at what doses. Although there are,
efforts underway within EPA to develop such information, a
clearly defined research strategy is required to focus the
scarce resources available to the Agency.
Strategies for assessing environmental exposures should be based
on the need for exposure characterizations in quantitative risk
assessment. Such a strategic approach is essential for EPA to
effectively carry out its risk assessment functions. At a
minimum, the overall strategy should address: interfaces between
the three principal methods of exposure assessment (personal
monitoring, modeling, and biomarkers); accountability of specific
research efforts to overall needs; long-term research commitment;
closer ties with other Federal agencies doing similar research;
and educational efforts,
In this report, we identify examples of research needed to
support a strategic research effort in exposure assessment.
These include research on acidic aerosols and gases,, biological
aerosols, environmental tobacco smoke (ETS), pesticides, volatile
organic compounds (VOC), and time-activity patterns and behavior.
We also identify the development of biological markers as a
promising form of research into determining human exposure.
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1.2 Recommendations
The following recommendations represent the most critical issues
that we believe the EPA should consider in developing its
research strategy for exposure assessment.
1.2.1 Establishment of an Agency-wide research program to
provide a basis for improved capabilities for quantitative
exposure assessment. Research needs which should be addressed
include:
a) development of sampling and analytical instruments and
techniques,
b) exposure models and their validation,
c) selection criteria for human populatipns and other
target species for exposure evaluations,
d) protocols for quality assurance of exposure data, and
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f) systems for exposure data management and access to data
banks.
1.2.2 Development of methods to optimize and facilitate
utilization of indirect indices of exposure, such as
environmental monitoring data (e.g., ambient air, drinking water)
and effects data (e.g., biomarkers, impacts on ecosystems).
1.2.3 Establishment of methods to derive the uncertainties of
exposure estimates based on both direct and indirect indices.
1.2.4 Use of the concept of total exposure, recognizing all
exposure pathways. Therefore, research should incorporate three
principal methods of exposure assessment - personal monitoring,
modeling, and biomarkers.
1.2.5 Utilization and development of resources in the academic
community to facilitate technical innovation and more universal
application of developments in exposure technology.
1.2.6 Establishment of a data management resource on exposure
data and encouragement of contributions and utilization by
program offices, other governmental agencies, the academic
community, and other interested groups.
1.2.7 An increased commitment to extramural research including
targeted requests for proposals to increase efficiency, and
greater use of the EPA Centers of Excellence program, providing
greater support to those Centers which assist the Agency in
achieving the goals laid out in its Research Strategy.
2.0 INTRODUCTION
2.1 Overview and Examples
The development of a strategy for research on exposure assessment
requires the definition of goals, a recognition of constraints,
and the examination of options for achieving the goals. The
choice of options should allow for contingency plans which would
permit adjustments in the strategy as conditions change.
A good example of a long term research effort with significant
payoff for EPA is the.Total Exposure Assessment Methodology
(TEAM) study. The success of this study has been dependent upon
basic approaches to:
a) analytic methodology capable of measuring relatively
minute levels of air pollutants,
b) technical developments leading to personal samplers,
c) fundamental improvements in sampling strategy related to
assessing individual and community exposures, and
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d) the recognition that EPA's focus should be on an
individual's total exposure to environmental health hazards.
Successful TEAM products could have been achieved far earlier by
EPA scientists if there was a recognition of the importance of
long term funding in this area by other EPA offices and by the
Office of Management and Budget (OMB).
The relevance of TEAM study findings includes the ability to
measure actual human exposure to volatile organic compounds and
to assess the relative importance of indoor vs. outdoor
exposures; including the recognition that for most toxic air*
pollutants the home is the major source of exposure. It has
provided techniques permitting EPA and state agencies to be
responsive to questions concerning extent of exposures in local
communities. Much more support of long-term studies of this
nature is necessary.
Another example of successful long term research in the
development and effective use of tools for exposure assessment,
is the study of lead exposure. This has increased understanding
of the multiple routes of entry of a single source. EPA in
essence has conducted a natural experiment by lowering airborne
lead through markedly decreasing allowable gasoline lead content.
This has produced a clearcut decrease in lead inhaled directly
from automobile exhaust. The larger part of the reduction in
body burden was due to a reduction in lead in automobile exhaust
which settles as dust on the ground where it can be eaten by
children who lick their fingers, where it can be stirred up by
human activities and inhaled, and where it can enter the food.
chain through deposition on edible foliage and through soil from
which it is taken up by growing plants.
Finally, we note the recent completion by EPA staff of the draftx
of an extensive Strategic Plan for Research on Total Human
Exposure to Environmental. Pollution. While the document is
misnamed in that it is really not focused on the strategic level,
it contains a good road map which lays out important options for
the approach to short term and long term research needs and can
profitably serve as a blueprint for agency actions. We
understand that a revised draft of the strategic plan is under
preparation.
Although these are good examples of relevant long-term research
efforts, there have been many opportunities missed because of the
relative paucity of long-term research in the area of exposure,
an area which is so central to EPA's mission. The Agency has a
need to develop a clearly focused centralized program of long
term research aimed at improving exposure assessment. In part
because of the relative lack of past efforts, and in part because
of the many exciting new advances in basic science pertinent to
improved exposure assessment, we are highly confident that a long
term research program of this nature will lead to major advances
of great value to EPA's regulatory decision making.
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2.2 Definition of "Exposure"
The term "exposure" is often used without clear definition. For
the purposes of this strategy statement, exposure is defined as
the environmental concentration of a substance in immediate
contact with an organism. Exposure is not synonymous with
"absorbed dose". To convert exposure measurements into absorbed
dose could require additional information on bioavailability,
uptake, and the efficiency of absorption.
2.3 Goal Statement
5.
The Agency's goal for research in exposure assessment should be
to develop a system which will provide the most accurate
determinations of exposure possible for any given set of
constraints. Central to all aspects of research into exposure is
the definition and reduction of uncertainties of the
determination arising from th~e assumptions in the conceptual
framework for making the determinations.
2.4 Categoriesof Exposure Determinations and Their
Limitations
Exposure determinations are made up of qualitative and
quantitative components, as described in more detail below. The
exact methods selected have a significant impact on the list of
chemicals which will be included and excluded from analysis. The
Agency needs to develop an assessment system which differentiates
between the inital reconnaissance stage, where qualitative
analyses should receive emphasis, and the definitive stage where
quantitative analyses should receive primary attention.
Determinations of exposure may be made by measurements, by
reconstruction, or by the use of mathematical models. The
uncertainties associated with each of these approaches can differ
greatly, and in many instances they have not been appropriately
defined.
Measurements taken in the immediate proximity of an exposed
organism are subject to the variabilities of local
concentrations, as well as errors introduced as part of
measurement techniques. When measurements are no longer made in
the immediate proximity of the organism, then additional
uncertainty accrues. Thus, the concentrations measured at an
ambient air monitoring station may have only a remote connection
with actual human inhalation exposures, which are mostly due to
indoor air. Similarly, concentrations of contaminants at the
municipal potable water plant may be poor predictors of actual
exposures from ingested liquids. A further complication is that
contamination of one medium can lead to exposure through another
medium; thus, contamination of potable water by volatile
compounds can lead to inhalation exposures.
Exposures may be inferred on the basis of observed retention or
effects in humans, using concentrations of substances or their
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metabolites in body fluids or tissues, or using other biological
markers. .These approaches directly estimate absorbed dose, rather
than exposure. In addition, they are often unable to distinguish
between shorter exposures at higher concentrations and longer
exposures at lower concentrations.
Exposures may be reconstructed by duplicating chemical releases
and measuring the resulting concentrations, or by modeling their
transport and fate from source to receptor. Lastly, exposures
may be derived from transport and fate models which stipulate
source terms, environmental conditions and tne location of the
receptor organism. Source terms may be based upon measurements or
may be assumed.
Both the costs and the uncertainties associated with these
various exposure determinations can greatly differ. Important
constraints for exposure assessment include: available resources,
area and duration of exposure assessment, exposure assessment
methods applicable to a specific problem, uncertainties
associated with a specific approach, and the precision and
accuracy requirements of the user of the exposure assessments.
These constraints impose opposing forces on the selection of
specific protocols for exposure assessments. For instance, under
certain conditions the available resources may allow only the
application of a very simple mathematical model, with a resulting
uncertainty which would make the exposure assessment valueless
for a subsequent risk assessment.
3.0 RATIONALE FOR EXPOSURE ASSESSMENT
Exposure assessments are integral requirements for risk
assessment, they are required to identify populations and
ecosystems at risk, and they are necessary to determine
compliance with certain standards. They are also important
components in the development of regulatory strategies. The
accuracy and precision of the exposure assessments obviously has
a major influence on the reliability of decisions which depend
upon such exposure assessments.
During his second tenure as Administrator (1983-1985) , Mr.
Ruckelshaus promoted the use of uniform, agency-wide risk
assessment procedures in the exercise of its regulatory
responsibilities. This approach has been highly successful in
some areas, but much less so in others. It has frequently been
limited by the lack of reliable information on exposure to
targets and receptors, i.e., to people, vegetation, fish, etc.
Experience has demonstrated that exposure assessment techniques
are at a relatively less advanced state than are techniques for
toxicity assessment, and that a sustained research program will
be needed to facilitate and encourage their use in the EPA's risk
assessment program. A long-term commitment to research in this
area will have immediate as well as long-term benefits to EPA.
This is based upon our belief that much of the exposure
technology that has already been developed has not been utilized
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by EPA, but could be after review and evaluation. In the longer
term, newer techniques and approaches can be developed,
validated, and applied.
4.0 APPROACHES TO HUMAN EXPOSURE ASSESSMENT
4.1 Overview
Exposures to a variety of environmental contaminants have been
shown to be associated with adverse health and comfort responses
in humans. Assessing human exposures to a single environmental
contaminant or group of contaminants is necessary in utilizing a
risk-based environmental management approach directed toward
determining the cause(s) of human health risks and formulating
cost effective mitigation efforts to reduce or minimize those
risks. Efforts to assess total human exposure to environmental
contaminants, and to develop effective measures to reduce those
exposures need to be guided by a theoretical framework or
methodology..
Central to the design of a human exposure assessment effort is
the identification of the health or comfort effect under study,
the ascertainment of the individual contaminant or general
category of contaminants thought to be associated with that
effect, and specification of the contaminant exposure on a time
scale corresponding to the effect. The impact of exposure to
environmental contaminants should,- ideally, .be evaluated in terms
of the dose of the contaminant or its metabolites received. Dose
can be considered as the internal dose (amount of the contaminant
deposited or absorbed by the body) or biologically effective dose
(amount of the contaminant deposited or absorbed which
contributes to the dose"at the cells where the effect occurs).
The use of dose (particularly the biologically effective dose) in
assessing the impact -of exposure to environmental contaminant(s)
is, however, often not practical since it can seldom be measured
directly. Exposure is generally the only direct link available to
the effect of interest. In fact, for regulatory and control
strategies the relationship between exposure and concentration in
air, water, soil, and food is of primary interest.
4.2 Methodologies
Assessment , of total human exposures to environmental
contaminant(s) must consider concentrations that occur in one or
more of the possible media of exposure (air, water, food and
soil), or through rates of uptake via routes of exposure such as
skin, ingestion, or inhalation. This approach is much broader
than the traditional EPA approach which considers exposures from
only one route of exposure and typically from only one
microenvironment within that media (e.g. air exposures with
specific focus on ambient air). Human exposures across all
environmental media can be assessed by three complementary
methods: personal monitoring, exposure modeling, and biological
markers.
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4.2.1 Personal Monitoring
Personal monitoring provides a direct measure of total human
exposure to environmental contaminant(s) of interest. This
approach involves the direct measurement of the pollutant
concentrations reaching the individual or population through all
media (air, water, food, and soil) integrated over some time
period. The emphasis in this approach is to directly measure
total exposure at the target to contaminant(s) emitted from
multiple sources and traveling along multiple routes of exposure.
Personal exposures are monitored over the course of normal
activity for appropriate periods of time ranging from several*
hours to several days. Integration over inappropriate times can
obscure toxicologically significant excursions in exposure.
4.2.2 Modeling
This approach conceptually combines monitoring of contaminants in
the media they occur, activity time budgets or food or water
consumption patterns and questionnaries to estimate (model) the
average exposure of an individual or population as the sum of the
levels of contaminant (s) in each media weighted by time in an
environment or quantity of food or water consumed. When personal
monitoring or media concentrations are not available or possible,
it may be necessary to model personal exposure from statistical
and/or physical models based on sources, transport and
transformation of constituents. However, models are based on
mathematical representations of physical and chemical processes.
The more complex the system,-the greater the uncertainty of the
results of the predicted exposures.
Questionnaires provide information on the media in which the
exposure takes place (e.g. physical properties of indoor
environment - sources, source use, ventilation, etc.) as an input
to the predictive model. The development of a predictive exposure
model attempts to measure and understand the basic.relationships
between causative variables and resulting exposures. Such models,
once validated, can then be used to estimate population exposures
of a wide range of potential mitigation efforts to reduce or
minimize exposures. It is the modeling which provides the
essential link between the exposures, the microenvironments or
media in which the exposures take place, and the factors which
determine the contaminant levels in the media and micro-
environments.
Environmental contaminant levels are the result of a complex
interaction of several interrelated variables in each medium
(e.g. air pollutant concentrations are a function of sources,
source use, meteorology, chemical reaction processes in air,
etc.). It is essential that exposure models incorporate data on
the factor controlling the exposures, so that cost efficient and
effective mitigation (risk reduction) can be instituted.
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4.2.3 Biomarkers
The term "biomarker" includes a large array of measurable
molecular constituents in humans. Such markers include residues
of chemicals and their metabolites in body tissues and fluids,
products of molecular changes such as DNA adducts and chromosome
aberrations, changes in levels of endogenously produced
molecules, and genetically determined biochemical
susceptibilities that vary among individuals. Such markers can be
used as indices of exposure, current disease state or
susceptibility to disease.
Biomarkers of exposure can theoretically integrate total intake
to the body from multiple sources of exposure to environmental
contaminants. If they are stable over time they can be used to
indicate levels of steady-state exposure. They can be useful
tools in elucidating mechansims of disease, or for extrapolations
between internal doses, routes of exposure, species or tissues.
They do not, however, necessarily provide the direct link between
environmental exposure and disease. Biomarkers may be measures of
the contaminant or its metabolites that are directly related to
the specific contaminant associated with the effect outcome (e.g.
lead) or may only be a surrogate for exposure to a complex source
of environmental contaminants (e.g. cotinine). The sole use of
biomarkers to assess exposure to environmental contaminants, like
the sole use of personal monitoring, can provide only limited
guidance in the selection of effective mitigation measures to
reduce exposures since biomarkers do not provide information on
the factors controlling exposure to the contaminant(s) in the
physical environment.
It is important that the Agency develop a system that can
effectively respond to information needs for risk based decision
making. One part of such a general system would be a sub-system
concerned with exposure determinations. Research problems in
exposure determinations are strongly linked to scientific
problems in transport and fate, and research on effects and risk
assessments. Important linkages also extend to areas such as
pollution control research. These linkages result in an
interdependence, so that decisions made in one area can have
strong effects on other areas.
Dealing with these complex relationships, as well as the
constraints mentioned previously, requires a systems approach in
which exposure assessment is one aspect of the entire
environmental assessment and management structure. Within the
area of exposure assessment, it is important to develop an
optimization among resources, uncertainties, and utilities.
4.3 Intermed ia Concerns
An obvious and well-documented problem in EPA's approach to
environmental pollutants is the strong tendency toward looking at
a pollutant in one medium only. Sometimes this has led to
regulatory approaches which control a pollutant in one medium by
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releasing it into another.
The physicochemical characteristics of the overwhelming majority
of common pollutants permit them to distribute in all media -
air, water, soil and food. Work done at an EPA research center
readily allows the prediction that leaky underground storage
tanks leading to groundwater pollution may result in greater
human exposure by inhalation due to offgassing from water than by
contamination of drinking water. Any attempt to ascertain the
potential impact of an environmental chemical should include
assessment of the extent of exposure in all relevant media. This
supports development of a centralized integrated approach t6
exposure which can consider long term needs in exposure
assessment.
5.0 ELEMENTS OF EXPOSURE
5.1 Overview
The studies of human exposure provide information that can fill a
basic need in risk assessment and risk management. These studies
can identify:
a) relative importance of different exposure pathways.-
b) quantify sources and or activities that contribute to
exposures
c) identify populations at differential risk
This information is essential to the design of public health and
cost effective strategies. For instance, the risk may be
unequally distributed across the population due to the influence
of specific sources or activity patterns. A mitigation strategy
aimed at a nation-wide reduction of emissions may be ineffective.
for the highest risk groups.
5.2 Components
.In order that exposure studies be useful to future decisions,
some basic components must be adequately addressed. These
components will determine not only the general ability of results
but the specificity of possible subsequent actions. Included in
these elements are:
a) Selection of representative sample,
b) Defining sample size,
c) Sampling, monitoring methods, and averaging times, and
d) Defining time-activity patterns.
Obviously these items are interrelated. The percent of people
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conforming to the specifications of the sampling protocol is in
part dependent on the details and complexity of the studies.
5.2.1 Selection of Representative Sample
There are well established methodologies for survey research. The
Agency has used proven survey techniques in the VOC and carbon
monoxide (CO) exposure studies. However, the participation rate
in exposure monitoring studies has been only approximately 50%.
The issues of selection bias must be addressed in future studies.
Experience indicates that both upper and lower economic groups
are less likely to participate. Studies do not have to be
designed to represent the entire U.S. or urban population, but
should include a suitable representation from a broad
representative cross section of the population.
Depending on the contaminant and distribution of sources, target
groups may be selected. Nevertheless, even these exposure studies
should use established survey research methodologies. At this
time, the difficulty with sample selection is the lack of
knowledge about the distribution and use of contaminant sources.
Without some prior knowledge, investigators must speculate on how
to over-sample low frequency categories. Therefore, a variety of
survey studies will be necessary.
5.2.2 Defining Sample Sizes
Determination of the number of participants in an exposure study
is a critical component. Representativeness and cost are obvious
tradeoffs. ,
Microenvironmental models are useful in determining sample size
by calculating the uncertainty in representing exposures in ^the
mean as well as percentiles. Microenvironmental exposure and dose
models must be developed and tested. In some cases, targeted
studies might be needed to develop the input conditions.
Statistical methodologies should be improved in the current
microenvironmental models. For some contaminants, the
concentrations co-vary with activities and for source use. Air
pollution dose will vary with activity level and anatomical
structure of the respiratory tract . among other factors. These
relationships must be better understood to advance
microenvironmental models.
5.2.3 Sampling. Monitoring Methods, and Averaging Times
Conducting human exposure studies will require the development of
new equipment and methods. Currently, information or actual human
exposures is limited, in part, because appropriate equipment and
methods do not exist for many contaminants. The exposure times of
interest can vary from a single breath to multi-year averages. It
is not practical to develop instruments and methods to cover all
averaging times and still have them inexpensive, light-weight and
durable for personal monitoring studies. However, EPA's engineers
and chemists should interact more closely with health scientists
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to define instrument needs with the appropriate time resolution.
This does not imply that exposures studies could not continue. A
combination of personal measurements with portable equipment and
fixed location microenvironmental measurements can provide needed
exposure data.
5.2.4 Time-Activity Patterns
Our population is very mobile. More is known about the movements
of working adults than of other groups. The time-activity
patterns of youth, retired individuals or people in general
during different seasons, climates, and weather conditions are?
not well described. The interactions or co-location of people and
pollution sources also are not adequately known. These are more
than subtleties. Knowing the indoor/outdoor concentration of
pollutants such as ozone and acid particles, and knowing the
outdoor time patterns of people with their activity levels allows
the calculation of exposure and possible dose on time scales
consistent with clinical studies. For some physiological
responses, exposures with time frames of minutes to hours are
more relevant than either our current standards or long-term
averages.
In general, human exposure studies need more carefully defined
averaging times. Studies of indoor, outdoor, and personal
exposures can be misleading if careful attention to averaging
times are not considered. It may be true that indoor
concentrations are highly correlated to personal exposures when
considering 24-hour or longer integrations. However, short-term
concentrations may be more relevant to a particular physiologic
effect.
Formaldehyde in homes illustrate a similar point. A combination
of increased emissions (because of thermal heating) and decreased
ventilation may result in transient sensory irritation and odor.
Averaging formaldehyde over 24-hour or a week with the current
survey instruments may indicate low average concentrations, which
may suggest that problem concentrations do not exist. Time
variation in indoor radon concentrations presents a similar
monitoring problem. Short-term charcoal grab samples may
misclassify a home where the longer term integration would be
more appropriate.
6.0 EXAMPLES OF EXPOSURE ASSESSMENT RESEARCH NEEDS
6.1 Exposure Assessment - General
a) Develop better understanding of time use patterns in our
society, how people spend time indoors and outdoors, and activity
levels associated with microenvironments.
b) Develop better understanding of ingestion of food, water,
and soils by segments of society.
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c) Population exposure studies, e.g., for criteria
pollutants, drinking water, pesticides, to determine
relationships among control strategies and public health
benefits, and to develop new exposure reduction strategies.
d) Where sources are indoors - understand patterns of use,
repair, maintenance and how these factors affect exposures.
6.2 Acidic Aerosols and Gases
The primary means of exposure to acid aerosols and gases is
through inhalation of their concentrations in the ambient air.
Although research has been conducted in this area, information on
the following is not well known:
a) Distributions of Hydrogen ion (H+) concentrations across
the United States in aerosols and vapors.
b) Deposition velocities.
c) Importance ' of facial and nasal deposition to sensory
irritation.
6.3 Exposures to Biological Aerosols
Evidence indicates that inhalation of aeroallergens, and
aeropathogens may be important contributors to respiratory
symptoms and illnesses. Investigations might lead to:
a) Quantifying relationships among questionnaires and actual
indoor concentrations of spores and other antigenic materials.
b) Knowledge about the variations in species and
concentrations within homes, offices, etc. and between
structures.
6.4 Environmental Tobacco Smoke (ETS)
Evidence indicates that exposures to ETS may lead to increased
respiratory symptoms in children, decreased lung performance and
perhaps lung cancer in adults. Nevertheless, there are still many
unresolved exposure issues.
a) Distribution of population ETS exposures is not known. It
would be worth while identifying high exposure group in addition
to characterizing factors influencing exposures.
b) Relationship between ETS environmental concentrations and
the deposited dose is important. The lung retention in children
as a function of age and activity would be important.
6.5 Pesticides
Pesticides are widely used in commercial buildings and
residences. Yet, the exposure to people in these settings by
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inhalation, contact or ingestion is not well characterized.
6.6 Volatile Organic Compounds (VOC)
Investigations of VOC's, particularly EPA's TEAM studies, have
revealed that for many compounds, exposure is dominated by the
indoor air contribution.
a) Repeat measures are needed to determine within-structure
variation.
b) The influence of source use on personal exposure needs to*
be determined for many VOC's.
c) Transportation among other microenvironments needs to be
studied.
d) Compounds studied must be expanded to include irritants,
immuno-toxic and neurotoxic materials.
6.7 Time-Activity Patterns and Behavior Factors
Extrapolating from a relatively few time-activity studies the
average employed person spends their time in the following
manner: 28% at work, 63% at home, 6% in transit, 1% in other
indoor locations and only 2% outdoors. For women not working out
of the home, the total indoor time is 94.1% with 4.2% in transit
and only 1.7% outdoors. Obviously on any given day, individuals
will .deviate substantially from these, average numbers. However,
there are, substantial gaps in understanding the time-activity
patterns in our society.
Knowing these patterns and the potential exposures to sources
and/or harmful substances would benefit environmental management
and policy decision. Time-activity surveys should be designed to
resolve behavioral patterns relevant to discerning human
exposures to environmental contaminants.
Factors that should be considered include:
a) Cross-section of population by age, sex, income, job
classification
b) Ethnic differences
c) Regional differences by season
d) Temporal differences by weather conditions
e) Level of activity (metabolism, minute ventilation)
f) Physical condition
g) Intra-regional differences by degree of urbanization
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7.0 BIOMARKERS OF EXPOSURE
Biological markers of exposure and/or effects are one of the most
promising avenues of research. A National Academy of Sciences
(NAS) Committee is in the process of evaluating the use of
biological markers in environmental health research. They have
defined biological markers as indicators of variation in cellular
or biochemical components or processes, structure, or function
that are measurable in biological systems or samples.
Markers can be divided into those reflecting exposure, effect, or
susceptibility. There is a continuum between exposure and effect
extending to overt human disease. The goals of research into
biological markers are the prevention and early detection of
human disease. Markers of exposure are particularly valuable in
reflecting the earliest steps in the process by which
environmental agents lead to adverse effects. Perhaps the ideal
marker is one which accurately indicates both exposure and
effect. A reasonable example is the formation of
carboxyhemoglobin (COHb), which provides an integrated measure of
exposure to carbon monoxide and is also the mechanism which is
responsible for the toxic effect of this gas. A marker of this
nature appears to be particularly suitable for what is now being
called biochemial epidemiology or molecular epidemiology. In the
past, occupational and environmental epidemiological studies have
generally used surrogates for exposure, e.g. job description,
geographical proximity to superfund site. Marked improvement in
the precision and effectiveness of epidemiological studies can be
obtained through the use of molecular markers of . exposure in
conjunction with outcome variables, if there is a well defined
Association between actual exposure and the biological marker.
The availability and development of biological markers stems in
part from rapid advances in our understanding of biological
processes, particularly in the exciting field of molecular
biology. Such techniques as the use of monoclonal antibodies,
recombinant DNA technology or Potassium-32 post-labelling to
detect DNA or protein adducts open whole new approaches to
biological markers for exposure and effect. These new
developments appear to promise the ability to determine the
extent of exposure of individuals to relatively low levels of
environmental chemicals. For example, it would not be surprising
to find through the use of sensitive biomarkers of exposure 'that
the bulk of a population living in the vicinity _o_f a hazardous
waste site has no more evidence of exposure to chemicals at that
site than does a control population; yet a few individuals,
through their activities at the site, or an unexpected exposure
route, will be found to have markedly elevated exposure. Of
particular importance will be studies to validate any markers
used in human studies. Furthermore, ethical issues raised by the
use of biological markers of exposure must be carefully
addressed.
The importance to EPA of improvements in biomarkers of exposure
is evident. EPA has invested heavily in the process of risk
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assessment as a tool for environmental decisionmaking and for
priority setting within the Agency: While there is much focus on
uncertainties on the hazard side of the risk assessment equation,
the uncertainties concerning exposure can often be greater.
The failure to appropriately perform exposure assessment at EPA
has perhaps nowhere been more evident than in the Tacoma smelter
situation. In the summer of 1983, EPA was faced with a specific
decision concerning instituting control technology on a smelter
which produced a substantial burden of arsenic to the local
community. The smelter was a major employer with much of the
local economy dependent upon its operation. Owners of ther
smelter claimed that they would close it down if they were forced
to spend substantial sums for air pollution control. William
Ruckelshaus, who had only recently returned to head EPA, decided
in essence to make this situation into a test case for the policy
of carefully communicating risks to the community so that the
community could discuss these risks intelligently and participate
appropriately in the decision process. Risks as high as one in
100 were computed for the immediate vicinity of the smelter with
lower risks for surrounding communities depending upon their
distance and the wind patterns.
Unfortunately, the exposures were estimated by a model in which
arsenic emissions were based upon the performance of a similar
smelter in another state. A wind rose was placed around this
point source, with the public assumed to be standing at their
front door breathing this arsenic level for 70 years. Not only
were ambient measurements not made, no advantage was taken of the
fact that urinary arsenic levels are an- excellent indicator of
arsenic exposure and body burden. In fact, urinary arsenic, which
already had been obtained by local authorities, clearly
demonstrated that EPA's exposure assessment had overestimated the
local exposure by a factor of about 15. In other words, when
Administrator Ruckelshaus told local people that their risk was
one in 100, an appropriate exposure assessment based upon a
biological marker would have led him to clearly state this
upperbound risk as being one in 1500.
It should be emphasized that the exposure assessment in the
Tacoma case was performed by the Program Office, without any
input from the Office of Research and Development
(ORD). It reflects an Agency-wide problem in that much exposure
assessment is actually performed within the various program
offices, using disparate approaches and unvalidated and
unpublished models. The SAB has frequently been critical of such
efforts, including the exposure assessment which forms a central
portion of the Integrated Environmental Management Program (IEMP)
of the Office of Policy, Planning and Evaluation.
There are numerous long range research opportunities for EPA in
the biomarkers area. It is important that as research proceeds
rapidly in assessing biomarkers of effect, e.g. the value of DNA
adducts in predicting cancer, that concomitantly research is
performed to link adducts of interest to exposure. Such
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biomarkers would be of particular value in determining the slope
of the lower end of the dose response curve for the effect of
chemicals, such as carcinogens, for which epidemiology or
standard laboratory animal safety assessment studies are
inherently inadequate.
Obtaining improved biomarkers of exposure is dependent primarily
upon long-term relatively basic research providing the
mechanistic understanding of the process by which exogenous
agents produce adverse effects.
8.0 STRATEGIES
8.1 Assessing Environmental Exposure
Strategies for assessing environmental exposures to environmental
contaminants should be based, in part, upon the need for exposure
characterizatons in quantitative risk assessment. For an agency
with as broad a range of mandates, responsibilities, and
capabiities as EPA, a strategic approach to exposure assessment
is essential for the effective execution of its risk assessment
functions. Adoption of such an approach will have the further
advantage of improving and unifying program office applications
of such assessments. The overall strategy will need to address
the following major issues: interfaces, accountability, long-term
commitment, other Federally funded research, and education.
8.1.1. Interfaces
Efforts to assess exposures to environmental contaminant(s) need
to recognize the role of the three principal methods of exposure
assessment (personal monitoring, modeling and.' biomarkers) and
incorporate into their study design, where feasible and
practical, several of the methods in order to more accurately
assess exposure and estimate dose. Such studies need to determine
the factors in the physical environment responsible for the
environmental concentrations, the multimedia routes of exposure
(air, water, eĢ.c.) and the number of microenvironments in which
exposures take place so that efficient and effective mitigation
measures to reduce exposure can be identified and evaluated.
Exposure studies should explore the use' of nested designs for
exposure assessment which utilizes all three methods to a varying
degree. Such efforts will require a fundamental change in the
EPA's current compartmentalized approach to exposure assessment.
8.1.2. Accountability
Research efforts to develop:
a) new or improved monitoring methods;
b) physical/chemical models for exposure assessment, and
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c) biomarkers, should be evaluated within the context of
their usefulness in an overall exposure assessment.
*
Existing information on environmental contaminant exposures
should be integrated into the process of setting research
priorities for all environmental contaminants. Funding decisions
should be tied to such a review and evaluation.
8.1.3. Long-term Commitment
*
Long term research on instrumentation for characterizing the
particle size distribution and the variation of chemical'
composition with particle size at the University of Minnesota's
Particle Technology Laboratory, largely with extramural support
from EPA, led to a marked improvement in our understanding of
particulate matter source contributions, long-range transport and
transformation, human exposure, and the factors influencing
atmospheric visibility. The contribution of the atmospheric
concentration data base, made possible by the development of this
new instrumentation, was a key factor enabling the EPA to develop
a new and tetter index of particulate air pollution which has
been incorporated in the 1987 PM^g National Ambient Air Quality
Standards (NAAQS).
*
Research in biocentration provides another example of valuable
returns from a long-term committment. The U.S. EPA developed many
of the basic concepts for the prediction of the bioconcentration
of important classes of organic compounds by fish. This work
contributed significantly to exposure assessments for consumers
of fish.
8.1.4. Other Federally Supported Research
Research pertinent to exposure assessment is being performed at
or under the auspices of a number of different Federal agencies,
ranging from the U.S. Geological Survey to the National
Institutes of Health. It is imperative that EPA establish closer
communication with these agencies, so that each can assist the
others in incorporating state-of-the-art knowledge in exposure
assessment. EPA's scientists need to attend national meetings and
keep in close contact with scientists who are performing the
basic research pertinent to long term improvements in exposure
assessment.
8.1.5. Educational Training
A Research Strategy should consider the establishment of a policy
to address the gaps and lack of synthesis in present approaches
to various environmental issues. This proposal is directed to
the establishment of educational programs and/or re-organization
of existing research centers focussed on environmental
assessment; both within the Agency and in academia, to integrate
the knowledge of specific disciplines.
Given the multiple-faceted nature of problems in all phases of
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the environment (air, water and land) and the multiple effects on
both humans and the ecology, and the relatively specialized
character of academic programs in health, science and
engineering, we recommend that EPA sponsor an academic Center of
Excellence (Research Centers Program) to serve as a focus for
both research and academic training in exposure assessment. This
would provide an ideal setting for multidisciplinary input from
various departments and schools within one or more Universities.
8.2 Exposure Assessment Planning
Strategic planning for exposure assessment will occur only when
agency staff with appropriate skills are provided with clearl^
stated responsibilities and budgets commensurate with the
agency's needs. Considering the breadth and diversity of these
needs, and the relatively primitive state of the art, the program
should be located within the Office of Research and Development
and should include the following major components: research,
coordination and technical support, development of an Agency-wide
program, and an outreach program.
Ŧ
8.2.1. Research in Exposure Assessment
L
A laboratory based program is needed to investigate and develop:
a) equipment and techniques for sampling and analysis of
environmental toxicants,
b) models for environmental transport and transformation of
.chemicals, and procedures for periodic model validation,
c) selection criteria for human populations and other target
species in the environment whose exposures may need to be
defined,
d) models for determining total exposure of populations to
environmental concentrations,
e) protocols for qualify assurance of data from
environmental measurements and models, and
f) systems for data management and its accessability to
agency staff.
8.2.2. Coordination and Technical Support
A headquarters based program is needed to develop exposure
assessment skills in ORD, program office, and regional personnel
and to provide technical support for the performance of
quantitative exposure assessments.
8.2.3. Development of Agency-wide Program
A headquarters based program is needed which would:
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a) identify agency needs in exposure assessment not being
addressed, and recommend action programs to the Administrator,
b) identify use of exposure assessment techniques in agency
offices, and evaluate them for consistency and reliability, and
c) set up, maintain, and promote the utilization of agency-
wide data base on exposure.
8.2.4. Outreach *
A headquarters based program is needed to exchange information
on exposure assessment techniques with other federal agencies and
state and local agencies and groups with interests in exposure
assessment. This could include, but should not be limited to
sponsorship of symposia and workshops, publication and
distribution of a newsletter., and preparation of published
Guidelines.
9.0 MONITORING AND RISK ASSESSMENT
9.1 Importance
*
When exposure assessments for risk assessments are needed, they
can sometimes be based on available data such as concentrations
in ambient air, drinking water, food, etc. Unfortunately, data
on concentrations in environmental media relevant to the specific
population or target of interest are. seldom available, even for
chemicals with established concentration or tolerance limits. In
such cases, reliance is placed on less direct and reliable
indices of exposure, such as estimates of locations of employment
or residence, combined with estimates of inhated and ingested
amounts and patterns of activity. Indirect human exposure data
based on tissue burdens of samples collected at autopsy have been
of great value to exposure estimation for pesticides, PCBs, and
other lipid soluble chemicals. However, the recent decision to
terminate the adipose tissue surveillance network will greatly
diminish the ability of the Agency to detect trends in population
exposure to a variety of toxic chemicals, such as pesticides,
dioxins from increasing incineration, and/or new toxic chemicals
entering the environment, or to determine the efficacy of the
implementation of controls.
9.2 Tools
The tools of exposure assessment are quite varied. They include
personal and portable monitors and samplers, highly sensitive
analytical procedures for trace concentrations in air, water,
food, excreta, blood, tissue specimens, etc., time-activity and
dietary diaries, data on dietary habits, and models to relate
such information to total or integrated exposure.
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9.3 What Can Be Done Now
For some airborne chemicals there are relatively inexpensive and
reliable passive monitors which can be used to determine
cumulative exposure (nitrogen dioxide, formaldehyde, radon).
Continuous measurements of exposure can be made with larger, more
complex, and more expensive personal monitors, such as for carbon
monoxide. Battery powered personal samplers can collect
integrated samples for a broandrange of gases, vapors, and
aerosols. Personal and other portable samplers can collect air
samples in selected micro-environments representative of human
occupancy. Market-based survey techniques can be used to collect
samples on a statistically reliable basis to determine ingestiort
exposures to a variety of chemicals. What can be done now is
generally limited by the costs of carrying out the studies.
Exposure to ecologic systems and other receptors for welfare
effects can often be measured by conventional techniques for
sampling air, precipitation, surface waters, and sediments, and
these samples can be analyzed by conventional techniques for
trace analyses. Indirect indices'of exposure include pathogenic
changes in receptors such as leaves which are characteristic for
known exposures. '
Exposures producing both health and welfare effects which are not
readily measured involve short-lived reactive chemicals such as
sulfuric acid, nitric acid, hydroxy radicals, and photosensitive
organics which may be difficult to collect on sampling
substrates, or which react, evaporate, or sublimate - between
sampling and analysis.
Indirect measures of exposure, especially analyses of blood (e.g.
carboxyhemoglobin, lead) can be excellent indicators of human
personal exposure. Biomarkers utilizing new knowledge in
molecular biology are beginning to be useful in indicating
exposure to mutagens and may become very useful and sensitive
indices of exposure.
9-4 Research Needs /
Research is needed on sampling and monitoring techniques for
chemically unstable and reactive materials, and for materials
lost by volatilization between sample collection and analyses.'
Research is also needed on time-activity patterns, dietary
patterns, and behavioral factors which can strongly modify
exposures within human microenvironments. Finally, research is
needed on exposure models which can utilize a variety of
available data on concentrations within environmental media,
time-activity and dietary patterns and yield total exposures to
individuals and populations. Further research is also needed to
validate such models and to determine their residual
uncertainties in quantitative terms.
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