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xvEPA
United States
Environmental Protection
Agency
Human Health
RESEARCH CONTRIBUTIONS REPORT
U.S. Environmental Protection Agency
Office of Research and Development
Washington, DC 20460
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Notice
This report has been reviewed and approved by the U.S. Environmental Protection Agency,
Office of Research and Development. Approval does not signify that the contents necessarily reflect
the views and policies of the Agency, nor does mention of trade names or commercial products
constitute endorsement or recommendation for use.
Acknowledgments
This document was prepared by Hugh Tilson, Director, Human Health Research Program,
Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park,
NC 27711, with contributions from research and communication staff.
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Contents
PageS
Introduction
Page 5
Overview of the Human Health Research Program
Page 9
Research Contributions
Page 21
Summary of Progress
Page 25
Future Directions
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Introduction
The mission of the U.S. Environmental Protection Agency (EPA) is clear—to protect human health and the
environment. Since its formation in 1970, EPA has made great progress in making the environment cleaner
and safer. However, today's remaining environmental issues are much more complicated than those 20-30
years ago. Scientific advances and technological developments, as well as a better understanding of factors
that pose risks to humans, have generated new concerns about environmental hazards and how best to protect
human health. More than ever, there is a need to look to the future, anticipate potential threats to human
health, and establish scientifically defensible approaches for addressing them.
Sound science is needed for EPA to determine and assess environmental problems that are the most
threatening to human health and our quality of life. In that regard, EPA's Office of Research and Development
(ORD) maintains several problem-driven research programs that address specific, short-term research gaps
identified by EPA's Program and Regional Offices (e.g., research on drinking water, water quality, global
change, air, and safe pesticides/safe products). EPA also supports two research programs, the Human Health
Research Program (HHRP) and the Ecological Research Program, that provide relevant research to support
problem-driven research efforts. HHRP provides an understanding of fundamental processes which underlie
environmentally related health problems and develops principles that are broadly applicable to a variety of
real-world environmental problems. The ultimate objective of the HHRP is to provide the scientific foundation
for regulatory decision-making.
This Research Contributions Report is intended to provide general background material about the HHRP and
to document significant milestones accomplished by the program over the last five years. The Overview section
describes the HHRP in the context of the overall research effort in ORD and delineates the four main themes
covered by the HHRP—research on biological mechanisms, cumulative risk, susceptible subpopulations,
and tools for evaluating risk management decisions. The Research Contributions section describes 11 major
accomplishments of the program. This research consists of multi-disciplinary, integrated efforts to address
significant research gaps facing EPA risk assessors and risk managers. The Summary of Progress section that
follows describes other accomplishments that represent important products produced by the HHRP. The Future
Directions section of this document builds on the program's accomplishments and describes the projected
direction of the research program for the next five years.
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Overview of the Human Health Research Program
EPA's Human Health Research Program (HHRP) in the Office of Research and Development (ORD) uniquely
integrates many environmental science disciplines to build a strong foundation for risk assessment and
improve understanding of toxic chemical exposure and health effects. The multidisciplinary program
coordinates fundamental research to fill gaps in scientific knowledge that will ultimately improve assessment
of public health risks and solve environmental problems.
The program is organized around four main themes to
address areas of research needed to advance risk assessment
capabilities. They are:
• BIOLOGICAL (MECHANISTIC) RESEARCH: To understand
underlying biological processes triggered when people are
exposed to environmental contaminants
• CUMULATIVE RISK RESEARCH: To evaluate what happens
when we are exposed to the many chemical mixtures in
our environment
• SUSCEPTIBLE SUBPOPULATION RESEARCH: To protect the
aging population, children, and those with chronic diseases
by providing new insights into how pollutants may affect
their health
• TOOLS FOR EVALUATING RISK MANAGEMENT DECISIONS:
To develop measurement tools and biological indicators
needed to assess the impact of regulatory decisions
on public health
We contribute to other research areas and programs in ORD
by providing broad and generic information that will help to
improve understanding of many environmental problems now
and in the future. For example, in order to develop approaches
to conduct risk assessments of mixtures of pesticides based on
mode of action, as required by the Food Quality Protection Act, it
is necessary to have some knowledge of the mode of action, i.e.,
how a contaminant interacts with the body. Our research makes
significant contributions to the pesticide research program by
providing fundamental knowledge about potential modes of
action that can be used for studying cumulative risk.
Our research focuses on developing a more systematic
understanding of the physical, chemical, or biological
processes that underlie how humans can be affected by
environmental agents. We develop broadly applicable research
tools for analyzing and using information in science-based
decision making. Thus we can generate data that can be used
to support EPA's risk assessments. The research is strategically
organized and planned to provide the methods, tools, and data
for addressing risk assessment needs.
For example, to prioritize pesticides and drinking water
contaminants for screening and testing, it is necessary to identify
the chemicals of greatest concern to public health. Human health
researchers have contributed in a strategic way to this hazard
identification effort. They have identified biological effects or
end points that can be incorporated into computational models for
predicting hazards, and they have identified key toxicity pathways
for use in physiologically based pharmacodynamic models that
can be used to predict adverse human health effects.
Projects are based on ORD's annual planning process, which
involves input and prioritization of research by the Agency's
Program and Regional Office risk assessors, risk managers and
other stakeholders. A multi-year plan for human health research
charts the course for the program over the next seven years to
provide significant outputs needed by EPA to make decisions
on protecting the public health. The multi-year plan for fiscal
years 2006-2013 is responsive to the needs identified by EPA to
advance risk assessment and address environmental problems.
www.epa.gov/osp/myp/HH%20MYP%20Final.pdf
The research program is evaluated through extensive independent
expert review by EPA's Board of Scientific Counselors (BOSC).
This evaluation assesses the development and application of
new human health research knowledge, as well as the relevance,
quality, and scientific leadership of the program. In 2005, the
BOSC Subcommittee for Human Health found that the Human
Health Research Program is of high quality, appropriately focused,
multidisciplinary, displayed good stakeholder participation,
informed risk assessments, and achieved the goal of reducing
uncertainty (www.epa.gov/osp/bosc). The BOSC Subcommittee
recommended greater involvement of stakeholders in the planning
and prioritization process, better articulation of the overall goals
of the program, and development of a framework for research
on tools for evaluating risk management decisions. We have
successfully integrated these practices into our research program.
To fulfill the mandate to protect human health, EPA uses a
process known as risk assessment to identify and characterize
environmentally related health problems. This process is an
integral component of environmental decision making under
regulatory statutes such as the Clear Air Act (1970), the Toxic
Substances Control Act (1976), the Safe Drinking Water Act
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There are many uncertainties associated with the
assessment of human health risk due to data limitations
and the complex relationship between source, exposure,
and biological response to environmental agents.
(1996), the Federal Insecticide, Fungicide and Rodenticide
Act (1996), and the Food Quality Protection Act (1996).
HHRP is designed to strengthen and advance this risk
assessment process.
Biological Research
There are many uncertainties associated with the assessment
of human health risk due to data limitations and the complex
relationship between source, exposure, and biological
response to environmental agents. Specific knowledge gaps
have been articulated by the scientific community (NRC,
1994; SAB, 1995; Presidential/Congressional Commission on
Risk Assessment and Risk Management, 1997) and EPA risk
assessors and risk managers (U.S. EPA, 2005).
For example, data on the biological response to environmental
agents is often gathered from laboratory animals under entirely
different sets of exposure conditions than humans may
experience. Therefore, extrapolating from laboratory animals
or cell culture systems to humans in assessing risk can be
uncertain. In the case of atrazine, a widely used herbicide,
HHRP science addressed this uncertainty, improving the risk
assessment. The research demonstrated that carcinogenic
effects in animals are not relevant to humans and that humans
are more likely to experience non-carcinogenic effects such as
developmental and reproductive dysfunction because of the
mode of action of atrazine.
Data available to risk assessors may be based on studies
that used moderate-to-high concentrations. Because most
real-world exposures occur at lower concentrations, risk
assessors must extrapolate from these higher-dose studies
to lower doses "real-world" exposure scenarios, which
can be problematic. Risk assessors and managers need
to understand better the linkages between environmental
exposures and how the chemicals are handled once they get
into the body, as well as how chemicals act on a target site
and the subsequent health effects. For example, in the risk
assessment for arsenic, dose-response information from ORD
was used to support the default risk assessment model (linear
model) for carcinogenic agents.
Cumulative Risk Research
In the past, evaluation of human health risk has focused
on a single chemical or single exposure pathway, e.g., by
inhalation only. However, most humans are exposed to many
environmental contaminants via multiple pathways and routes.
Such combinations could result in unexpected aggregate or
cumulative effects. The combined risk from such exposures
may be greater or less than what would typically be predicted
from data on individual chemicals with single routes of exposure
(U.S. EPA, 2000). Furthermore, it is now clear that people are
exposed to many stressors— chemical and non-chemical—and
risk assessors and risk managers often are confronted with
assessing risks in populations residing in specific geographical
locations. HHRP research established a common mode
of action for the chlorotriazine class of pesticides, and this
information was used to support the default assumption of
additivity—the interaction of chemicals with one another—in
the cumulative risk assessment for this class of compounds.
Susceptible Subpopulation Research
Human variability in exposure and response to environmental
agents is a key uncertainty in assessing human health risk.
The Safe Drinking Water Act (1996) requires EPA to consider
risks to groups within the general population that are identified
as being at greater risk of adverse health effects, including
children and older adults. Similarly, the Food Quality Protection
Act (1996) contains special provisions for the consideration
of risks of pesticide exposure in children. Risk assessors and
risk managers need to know the scientific basis for identifying
and protecting susceptible subpopulations in the evaluation of
environmental agents for potential human health risk. HHRP
research with laboratory animals found an increased sensitivity
of younger animals to the toxic effects of chlorpyrifos, and this
information was used to help support the application of a safety
factor to protect children's health.
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Tools for Evaluating Risk Management
Decisions
Ensuring that pollution control programs produce measurable
benefits in human health is fundamental to the mission of EPA
to protect human health and the environment (U.S. EPA, 2003).
It is increasingly important to assess the effectiveness of EPA's
tools, approaches, and indicators to demonstrate the success of
its risk management decisions. However, current health status
trends in the U.S. and tools to determine the impact of regulatory
decisions on exposures to environmental stressors that lead to
adverse health outcomes are not widely understood.
ORD has started to focus much of its research effort on the
issue of evaluating risk management decisions. The objectives of
research in this area are to develop and validate environmental
public health tools, approaches, and indicators that can be used
to reflect the actual impact of environmental decision making
on public health and to help clarify the health benefits and
financial costs associated with further incremental environmental
improvements. EPA is supporting two demonstration projects
designed to develop principles to verify the protective benefit
of environmental decisions. One is assessing reductions in
waterborne illness from Safe Drinking Water Act regulations and
the other is evaluating the impact of a "Clean Air Initiative" on
environmental indicators in children and the elderly.
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Research Contributions
BIOLOGICAL (MECHANISTIC) RESEARCH
Research Leading the Way in
Understanding Dioxin Risks Standards
ISSUE:
Dioxins are a byproduct of routine combustion processes such
as the burning of household trash, commercial or industrial
incineration, volcanic eruptions, and forest fires. They tend to
accumulate in the fatty tissue of the animals we eat. Numerous
studies have shown that human exposure to high levels of
dioxins can produce serious adverse health effects. Even
extremely small exposures may be problematic.
chemicals that are structurally related, act in the same way,
and cause the same effect. And finally, while there is some
debate among scientists as to whether humans are as sensitive
to dioxins as are other animals, HHRP's work has added to
the evidence that people are indeed very sensitive to
dioxin exposures.
In the United States, the potential human health risks associated
with dioxin contamination has led to voluntary industry practices
limiting the levels in certain consumer products. Major sources
from 20 years ago have been largely eliminated.
SCIENCE OBJECTIVE:
Researchers in the U.S. Environmental Protection Agency's
Office of Research and Development are contributing to the
assessment of dioxin contamination in several significant
ways. First, they have introduced the concept of using what is
known as steady state body burden as the primary measure of
exposure. Traditionally, scientists might simply look at how much
of a chemical was ingested or came into contact with someone's
skin -what's called a daily dose. But because dioxins are so
persistent, remaining in the environment and in the body for
years, it is important to know what was eaten yesterday, last
month, and even ten years ago, to produce the total amount
that's in the body - the steady state body burden.
Human health research also supports a method of assessing
exposure to mixtures of dioxins that is called the toxic
equivalency (TEQ) approach. Essentially, this approach takes
an integrative measure of the potency of each compound (the
Toxic Equivalency Factor, or TEF) and multiplies it by the total
exposure amount to assess risk. This method underscores the
concept that risk assessment of chemicals not only involves a
measurement of how much but also how dangerous.
Finally, the Agency has introduced the concept of human
relevance in the study of dioxin contamination. This concept
considers that the effects of dioxins are not unique to a particular
species; they cause similar effects in most every species.
APPLICATION AND IMPACT:
Research is helping to guide the world's ability to assess dioxin
contamination and reduce the potential for human exposure.
For example, the method used to determine steady state
body burden is now the widely accepted standard method
for measuring dioxin contamination as well as all persistent
chemicals. Similarly, the toxic equivalency factor approach is the
international standard for assessing exposure to combinations of
dioxins and is the accepted method for measuring all persistent
REFERENCES:
DeVito M.J.; Birnbaum L.S.; Farland W.H.; Gasiewicz T.A. Comparisons of
estimated human body burdens of dioxinlike chemicals and TCDD body
burdens in experimentally exposed animals. Environ Health Perspect,
1995 Sep; 103(9):820-31.
Birnbaum L.S.; Tuomisto J. Non-carcinogenic effects of TCDD in animals.
Food Addit Contam. 2000 Apr;17(4):275-88.
Contact. Linda S. Birnbaum, Ph.D., D.A.B.T., EPA's Office of Research
and Development, 919-541-2655, Birnbaum.Linda@epa.gov
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Research Addresses Potential Risks of
Atrazine and Related Pesticides
ISSUE:
Atrazine is an agricultural herbicide used worldwide since
1958. In the United States, approximately 75 million pounds of
atrazine are applied each year, making it the most widely used
agricultural herbicide. In states where atrazine is heavily used,
the chemical has been found in both surface and groundwater.
Consequently, scientists with the U.S. Environmental Protection
Agency's Office of Research and Development are studying
atrazine to understand if the herbicide has human health
implications.
SCIENCE OBJECTIVE:
Atrazine and other chlorotriazines are being reviewed by EPA
because they are widely used and have been reported to cause
adverse health effects in the aging female rat. Ongoing research
to identify the range of biological effects and the mode and
mechanism of action through which atrazine has its primary
effect on endocrine function is important in understanding how
the herbicide impacts laboratory animals and potentially
human health.
APPLICATION AND IMPACT:
Research on atrazine demonstrated that effects in animals of
initial concern (mammary cancer) were not likely to be relevant to
humans. The mode of action for atrazine suggests that humans
would be at risk for different toxic effects such as premature aging,
developmental effects, reproductive function, and delayed puberty.
Investigators found that atrazine alters the way the brain controls
pituitary function, an observation that would be consistent with
atrazine-induced premature aging. They found that atrazine
suppressed two hormones-the luteinizing hormone (LH) and
prolactin hormone (PRL) - by altering the hypothalamic control of
pituitary hormone secretion. Although scientists are still studying
the precise mechanism through which atrazine causes these
changes, they have demonstrated the adverse outcomes of the
changes in LH and PRL.
Research showed that a brief atrazine exposure to a lactating
mother can influence development in the offspring by modifying
endocrine constituents of the mother's milk. Second, this work has
identified a sensitive period of time for this type of early lactation
exposure and raises the issue of whether other environmental
compounds may similarly affect reproductive function in the
offspring of mothers exposed to atrazine and potentially other
similar chemicals.
Other HHRP research showed that juvenile exposures to atrazine
and the primary metabolites of atrazine result in delayed puberty
in the male and female rats. Three of the primary metabolites of
atrazine appear to be just as potent as the parent compound in
inducing these effects on pubertal development. The research has
had a valuable impact on the risk assessment for this chemical.
Data has been used to set the no effect level for the developing
animal and to understand cumulative effects of atrazine and
its metabolites.
REFERENCES:
Stoker, I.E.; Robinette, C.L; and Cooper, R.L. Maternal exposure to
atrazine during lactation suppresses suckling-induced prolactin release
and results in prostatitis in the adult offspring. Toxicological Sciences.
1999, 52(l):68-79.
Cooper. R.L.; Stoker, I.E.; Tyrey, L; Goldman, J.M.; McElroy, W.K.
Atrazine Disrupts the Hypothalamic Control of Pituitary-Ovarian Function.
Toxicological Sciences. 2000, 53: 297-307.
Laws, S.C.; Ferrell, J.M.; Stoker, I.E.; Schmid, J.; and Cooper, R.L. The
effect of atrazine on puberty in female Wistar rats: an evaluation in the
protocol for the assessment of pubertal development and thyroid function.
Toxicological Sciences. 2000, 58(2): 366-76.
Contact. Ralph L. Cooper, Ph.D., EPA's Office of Research and
Development, 919) 541-4084, cooper.ralph@epa.gov
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Research Shows the Potential Impact of
Chemical Mixtures on Thyroid Function
ISSUE:
Chemicals pervade our world - in the air we breathe, the water
we drink, and the products we use. The HHRP constantly
studies the many ways our bodies are affected by different types
of chemicals. In one area, scientists are learning more about the
risk of simultaneous exposure to multiple chemicals that disrupt
thyroid hormones. A goal of this research is to protect the most
sensitive populations, especially children and older adults, from
adverse effects on the development of their nervous systems.
Proper thyroid operation is essential for the developing child
before and after birth, and for a number of physiological
processes in adults. It's widely known in the scientific
community that a number of individual chemicals on their
own and at high concentrations can lead to disruption of
thyroid activity. Relatively little is known, however, about how
combinations of chemicals at natural exposure levels affect the
thyroid. For example, are mixtures of such chemicals additive,
synergistic or antagonistic? In other words, do their effects
simply combine, multiply upon combination, or tend to cancel
each other out?
SCIENCE OBJECTIVE:
A team of researchers with HHRP designed a study to test the
additivity theory for a large mixture of polyhalogenated aromatic
hydrocarbons (PHAH's), a family of chemicals that are known
to disrupt thyroid activity. At low dosing, researchers concluded
that the thyroid disrupting chemicals interacted in an additive
manner in an animal model. This suggests that while each
individual chemical alone may not be enough to cause any
noticeable effect, the cumulative affect of several chemicals
could. At higher exposures, above those to which humans are
normally exposed, researchers found a small synergistic effect
on thyroid hormone disruption, meaning that the affects of the
chemicals don't simply accumulate; essentially, they multiply
by some new factor.
APPLICATION AND IMPACT:
Research analyzing the additive effect of thyroid disrupters
is illustrating the importance of studying chemical mixtures
and the potential impact on human health. This research is
filling knowledge gaps and providing critical science needed to
improve the ability to assess the risk of multiple chemicals that
impact thyroid function. Research in this area falls under the
Food Quality Protection Act (FQPA) of 1996 which mandates the
assessment of risks that result from exposure to multiple,
similar-acting chemicals.
Ongoing research will provide a broader understanding of the
ways in which chemicals interact to disrupt the functioning
of thyroid hormones, providing important information to
environmental risk assessors and managers.
REFERENCES:
Whyatt, R.M.; Camann, D.; Perera, P.P.; Rauh, V.A.; Tang, D.; Kinney,
PL; Garfinkel, R.; Andrews, H.; Hoepner, L; Barr, D.B. Biomarkers
in assessing residential insecticide exposures during pregnancy and
effects on fetal growth, Toxicology and Applied Pharmacology 2005,
206: 246-254.
Lu, C.; Showlund-lrish, R.; Fenske, R., Biological monitoring of diazinon
exposure using saliva in an animal model, J. Toxicol. Environ Healt
2003, 66:2315-2325.
Williams, M.K.; Barr, D.B.; Camann, D.E.; Cruz, L.A.; Carlton, E.J.;
Borjas, M.; Reyes, A.; Evans, D.; Kinney, P.; Whitehead, R.D.; Perera,
F.P; Matsoanne, S.; Whyatt, P.M.. An intervention to reduce residential
insecticide exposure during pregnancy among an inner-city cohort,
Environmental Health Perspectives,November 2006, Vol. 114, No. 11.
Contact. Kevin M. Crofton, Ph.D., EPA's Office of Research and
Development, 919-541-2672, crofton.kevin@epa.gov
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Research Contributes to Cumulative
Risk Assessments for Organophosphates
ISSUE:
Organophosphates are pesticides used in agriculture and
non-agriculture settings that affect functioning of the human
nervous system through inhibition of a specific enzyme. They
are among the HHRP's first priority group of pesticides to be
reviewed under the Food Quality Protection Act (FQPA) of 1996.
The act mandated a re-evaluation of tolerances for pesticides by
2006, in consideration of the human health effects that result
from exposure to two or more chemicals that act in a similar
fashion. The Agency was able to meet the requirements of that
mandate by developing and conducting a complex assessment
of cumulative exposure and risk to human health from
these pesticides.
SCIENCE OBJECTIVE:
HHRP scientists in the Office of Research and Development
developed a more thorough examination of risk associated
with commonly used pesticides. Since the routinely used
Organophosphates all have a similar mode of action, which is to
say they all inhibit the enzyme acetylcholine esterase [AChE],
they were selected for the first cumulative risk assessment
conducted by EPA. This assessment evaluates the potential for
people to be exposed to more than one organophosphate at a
time and considers exposures from food, drinking water, and
residential sources. In addition, this evaluation considers a full
set of reliable assessments of toxicity to characterize the potential
risk of cumulative exposure to Organophosphates.
Several aspects of this assessment represent an advance
on previous practice, leading to a far more comprehensive
and accurate method of assessing exposure to similar-acting
pesticides. The prevailing practice has been to select a single
experiment with which to characterize potency; in this study
all reliable experiments were used. This gives a more robust
estimate of potency and allows a more refined look at the
relationship between dose and effect.
APPLICATION AND IMPACT:
This research program has reduced uncertainty in risk
assessment in several significant ways. First, it has demonstrated
the usefulness of HHRP methods, tools, and data, as well
as an innovative approach for conducting cumulative risk
assessments under the FQPA mandates. The research program
also has improved understanding of exposure scenarios, key risk
factors, and biological mechanisms that point to the usefulness
of additional safety factors when analyzing whether pesticide
usage poses health risks to susceptible populations. From that
knowledge, several Organophosphates that previously had been
in use have since had their availability canceled or curtailed.
The program also has served to provide a basis for assessing
risks from other classes of pesticides that come under the FQPA
mandate. This broad new framework can be considered by
Agency risk assessors when addressing cumulative risks to other
classes of compounds and mixtures.
REFERENCES:
Setzer, W.; etal. Research Supporting the Relative Potency Factor
Assessment of OP Pesticides, Poster LTG 2-12 for BOSC Review.
April 25, 2005.
U.S. Environmental Protection Agency Web site, www.epa.gov/pesticides/
cumulative/rra-op/, Organophosphate Pesticides: Revised Cumulative
Risk Assessment. June 2002.
Contact. R. Woodrow Setzer, Ph. D., EPA's Office of Research and
Development, 919-541-0128, Setzer.Woodrow@epamail.epa.gov
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Researchers Develop Model to Estimate
Cumulative Exposures to Chemicals
ISSUE:
On a daily basis people encounter a variety of chemicals that enter the
body through food, water, air, and skin. Scientists are developing the tools
necessary to estimate how we are exposed to different chemicals and to
understand better the human health risks from daily exposure to mixtures
of chemicals. New and sophisticated computer models are needed to
simulate the concentrations of pollutants that people come in contact with
during their daily activities. The need for reliable probabilistic models of
human exposure is critical as EPA considers cumulative exposures in
its risk assessments.
SCIENCE OBJECTIVE:
The Stochastic Human Exposure and Dose Simulation (SHEDS)
Multimedia Model developed by HHRP is the primary tool used for
simulating exposures to a variety of chemicals that enter the body in
multiple ways. This model predicts, for specified populations, human
exposures to chemicals from eating, drinking, and breathing, as well
as from contacting surface residues and from hand-to-mouth and
object-to-mouth ingestion. To perform these calculations, the model
combines information on chemical use, human activities, environmental
residues and concentrations, and other important exposure factors, using
probabilistic sampling methods. The model enables decision makers
to address questions like:
• How do chemicals distribute into the air and on to surfaces under
real-world use or application scenarios?
• What are populations' real-world exposures for different
chemicals/chemical classes?
• Which exposure pathways are the most important?
REFERENCES:
Hore P.; Zartarian V.; Xue J.; Ozkaynak H.; Wang S.W.; Yang Y.C.; Chu PL;
Sheldon L; Robson M.; Needham L; Barr D.; Freeman N.; Georgopoulos
P.; Lioy P.J.; Children's residential exposure to chlorpyrifos: Application of
CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/
SHEDS-Pesticides model, Sci Total Environ. 2005, Decl4; Epub ahead
of print].
Zartarian V.G.; Ozkaynak H.; Burke J.M.; Zufall M.J.; Rigas M.L.; FurtawJr.
E.J.; A modeling framework for estimating children's residential exposure
and dose to chlorpyrifos via dermal residue contact and non-dietary
ingestion, Environmental Health Perspectives 2000, 108(6):505-514.
Contact. Valerie G. Zartarian, Ph.D., EPA's Office of Research and
Development, 617-918-1541, zartarian.valerie@epa.gov
APPLICATION AND IMPACT:
The dietary (food and drinking water) component of the SHEDS-MuItimedia
model has been applied to support EPA's cumulative risk assessment for
n-methyl carbamate pesticides. The SHEDS-Multimedia dietary module can
be used to answer regulatory-related questions regarding the contribution
of different foods and number of eating occasions. The SHEDS-Multimedia
algorithm for simulating children's exposures via hand-to-mouth contact
was used in EPA's final n-methyl carbamate assessment.
Ongoing modeling research is focused on developing a publicly available,
state-of-the-science modeling tool for improving estimates of human
exposure to multimedia, multipathway chemicals. This research is
identifying critical exposure routes, pathways and factors to help guide
future field study measurements and is expected to provide probabilistic
exposure assessments that can help reduce uncertainty in risk
assessments and enhance risk management decisions.
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Research Models Estimate Exposure to
Chromated Copper Arsenate (CCA)
from Playsets and Decks
ISSUE:
Little is known about the potential health risks to young
children who play on or around wooden structures treated
with a chemical preservative known as Chromated Copper
Arsenate (CCA). CCA-treated wood is most commonly used in
outdoor settings for decks, walkways, fences, gazebos, boat
docks, and playground equipment to protect wood from dry
rot, fungi, molds, termites, and other pests. The compound
contains chromium, copper, and arsenic. Arsenic is a known
carcinogen that has been shown to increase the risk of certain
types of cancer. However, information is needed on real-world
exposures to estimate potential health risks.
on the wood, 3) the surface area of the child's hands that are
mouthed, 4) the amount of time a child plays on or around
treated playsets, and 5) how often the child's hands are washed.
APPLICATION AND IMPACT:
The SHEDS-Wood model exposure estimates are being used
in EPA's risk assessment for CCA. As a result of this research,
EPA has the data needed to advise the public on how to limit
children's exposure. In addition, the findings are informing overall
risk management strategies and providing the science needed to
make decisions regarding re-registration eligibility for CCA.
HHRP is conducting additional studies to evaluate the
effectiveness of different wood sealants on reducing arsenic
residues in treated wood and surrounding soil.
SCIENCE OBJECTIVE:
To understand the extent to which children are exposed to
arsenic and chromium while playing on or around CCA-treated
playground equipment and residential decks, scientists from
HHRP's Office of Research and Development used a simulation
model to predict human exposure. The Stochastic Human
Exposure and Dose Simulation model for wood preservatives
(SHEDSWood) is a probabilistic computer model which allows
researchers to estimate exposure from skin contact with treated
wood and nearby soil, and from ingesting wood residues and soil
around playsets and decks.
The results have shown that children are exposed to CCA
chemicals the most when they put their hands in their mouths
after playing on CCA-treated wood. The research also showed
that there are several variables that impact exposure the most
including: 1) the ease with which residue on the wood surface
can be transferred to children's skin, 2) the amount of residue
REFERENCES:
Zartarian, V.G.; Xue, J. ; Ozkaynak, H.A. ; Dang, W.; Glen, G.; Smith, L.;
and Stallings, C. A Probabilistic exposure assessment for children who
contact CCA-treated playsets and decks using the stochastic human
exposure and dose simulation model for the wood preservative scenario
(SHEDS-WOOD), U.S. Environmental Protection Agency, Washington, DC,
EPA/600/X-05/009.
Zartarian.V.; Xue, J.; Ozkaynak, H.; Dang, W.; Glen, G; Smith, L;
Stallings, C. A probabilistic arsenic exposure assessment for children
who contact CCA-treated playsets and decks, Part 1: model methodology,
variability results, and model evaluation. Risk Analysis 2006, Vol. 26, No.
2, 515-531.
Xue, J; Zartarian, V.; Ozkaynak, H.; Dang, W.; Glen, G; Smith, L; Stallings,
C. A. Probabilistic arsenic exposure assessment for children who contact
Chromated copper arsenate (CCA)-treated playsets and decks, Part 2:
sensitivity and uncertainty analyses. Risk Analysis 2006, Vol. 26, No. 2,
533-541.
Contact. Valerie G. Zartarian, Ph.D., EPA's Office of Research and
Development, 617-918-1541, zartarian.valerie@epa.gov
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Research Shows How Biomarkers Can be
Used to Understand Environmental Exposures
ISSUE:
Every day, people come into contact with a variety of environmental
chemicals through the food they eat, the water they drink, the air they
breathe, and objects they touch. This contact with chemicals- known
as exposure - affects everyone. To understand exposures and their
potential health risks, HHRP scientists are working to identify tools,
called biomarkers, that can be used to assess a person's exposure to
chemicals and, in some cases, identify an early health effect from the
exposure. Biomarkers are substances, structures or processes that can
be measured in biological samples (such as urine, blood, or saliva) that
indicate an exposure or susceptibility, or predict the incidence or outcome
of disease. They help us to understand how chemicals move through the
body and cause biological changes that can lead to illness and disease.
SCIENCE OBJECTIVE:
Scientists in biomarkers research are developing and validating
biomarkers that can be used in clinical screening, epidemiological
studies, and risk assessments. The EPA's Science to Achieve Results
(STAR) grants program supports biomarkers research including:
• MECONIUM VALIDATION STUDIES. Researchers have studied
meconium, an infant's first set of stools, as a potential biomonitoring
matrix for analyzing fetal exposure to pesticides.
• SALIVA RESEARCH. Saliva offers an easy, noninvasive way to collect
samples for assessing exposure to chemicals. Several projects have
demonstrated that saliva is a useful biomarker for measuring children's
exposure to pesticides.
• APPLICATION OF BIOMARKERS IN EPIDEMIOLOGY. Research has
incorporated biomarkers of exposure (for example, organophosphate
metabolites) into epidemiology studies in the U.S. and internationally.
APPLICATION AND IMPACT:
Biomarkers help scientists understand what makes some individuals
or groups of people more susceptible to the harmful effects of toxins.
Biomarkers also can be used to improve risk assessment and evaluate
the impact of regulatory actions. Biomarker research has provided
data showing that EPA regulatory action was successful at reducing
prenatal exposures to certain insecticides among African-American
and Dominican mothers and newborns in New York City. Researchers
also have shown that saliva can be used as a simple and noninvasive
biomarker to measure exposure to certain pesticides in both children
and adults. In another study, researchers used validated biomarkers to
demonstrate that pest management techniques provided an effective
strategy for reducing internal doses of pesticides during pregnancy.
REFERENCES:
Whyatt, P.M.; Camann, D.; Perera, P.P.; Rauh, V.A.; Tang, D.; Kinney, PL;
Garfinkel, R.; Andrews, H.; Hoepner, L; Barr, D.B. Biomarkers in assessing
residential insecticide exposures during pregnancy and effects on fetal
growth, Toxicology and Applied Pharmacology 2005, 206: 246-254.
Lu, C.; Showlund-lrish, R.; Fenske, R., Biological monitoring of diazinon
exposure using saliva in an animal model, J. Toxicol. Environ Healt.
2003, 66:2315-2325.
Williams, M.K.; Barr, D.B.; Camann, D.E.; Cruz, L.A.; Carlton, E.J.;
Borjas, M.; Reyes, A.; Evans, D.; Kinney, P.; Whitehead, R.D.; Perera,
P.P.; Matsoanne, S.; Whyatt, P.M., An intervention to reduce residential
insecticide exposure during pregnancy among an inner-city cohort,
Environmental Health Perspectives, November 2006, Vol. 114, No. 11.
Contact. Kacee Deener, M.P.H., EPA's Office of Research and
Development, 202-343-9852, Deener.kathleen@epa.gov
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Human Health Research Supports
National Buy Clean Program
ISSUE:
Cleaning products are widely used in schools, offices, and
homes to keep hard surfaces such as furniture, floors, and toilets
sanitary. Some of these consumer products may pose potential
health risks. Cleaning products are known to generate emissions
that potentially have adverse health effects.
EPA's national buy clean program promotes the purchase
of products and services that contribute to healthy indoor
environments in schools and identifies effective ways to develop,
market, and buy lower-risk products. HHRP scientists are
evaluating these cleaners so that schools and building managers
can select the least hazardous products and reduce human
exposure to these chemicals.
SCIENCE OBJECTIVE:
The objectives of research on hard-surface cleaners are twofold:
to identify the major volatile chemicals - that is, those that are
easily released into the air - in commercially available products,
and to develop screening methods to estimate potential
exposures. Scientists identified potential hazardous chemicals
in cleaners by reviewing individual material safety data sheets
developed by the product manufacturers, and developing and
evaluating models to screen emissions.
The review identified more than 150 chemical ingredients in the
267 cleaning products analyzed. They include hazardous air
pollutants (HAPs) such as glycol ethers, hydrochloric acid, and
methanol. In addition, other chemical ingredients found in the
cleaning products include 28 that are regulated by occupational
standards; some of these are potential irritants while others
can affect the central nervous system. Through these findings,
researchers have concluded that products containing high
concentrations can produce adverse health effects.
Two models have been developed to screen emissions. The first,
called the film model, estimates the potential exposure from the
liquid cleaning products applied to hard surfaces such as furniture
and floors. The other, the bucket model, estimates exposure to a
worker or others due to emissions generated from the product in
a bucket or other container used during cleaning. The film model
has potential as a screening tool to compare the cleaner products
and to select less hazardous ones.
APPLICATION AND IMPACT:
The results of this research are being used by EPA to develop
control techniques guidelines for industrial cleaning solvents.
REFERENCES:
Potential Inhalation Exposure to Volatile Chemicals in Water-based
Hard-surface Cleaners, U.S. EPA, Washington, DC,
EPA/600/R-05/005, 2005
For more information on environmentally preferable products, visit, http://
cfpub.epa.gov/schools/top_sub. cfm?t_id=45&s_id=28.
Contact. Zhishi Quo, Ph.D., Environmental Scientist, EPA's Office of
Research and Development, 919-541-0185, guo.zhishi@epa.gov
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Research Shows the Role of Mold in
Causing or Exacerbating Asthma
ISSUE:
The number of Americans diagnosed with asthma, particularly children,
has reached epidemic proportions. To improve understanding of the
human health implications of asthma, HHRP has developed a targeted
asthma research program.
One area of asthma research involves the potential role that mold plays
in the development or exacerbation of asthma. Recently, there has been
much media attention devoted to Stachybotrys chartarum, a type of black
mold or fungus that has been associated with a range of health problems
including asthma.
SCIENCE OBJECTIVE:
Few hypotheses about mold exposure, its influence on asthma, or
methods for prevention have been tested scientifically. As a result,
HHRP has made mold, or fungal bioaerosols, a major focus of its asthma
research program.
Researchers are currently working to identify and describe the many
different molds commonly present in household environments. They hope
to determine which molds pose the greatest risks and whether any has
the capacity to cause asthma.
Scientists also intend to determine how much mold a person must inhale
to cause an effect. Inhaling just a few particles may sensitize people's
lungs, making them more likely to react to future exposure. In addition,
genetic variations in humans may cause cells to respond differently which
may explain why mold and other allergens cause or exacerbate asthma
in some people but not in others. Researchers are working to determine
the specific ways in which cells and organs respond to molds and other
environmental pollutants.
APPLICATION AND IMPACT:
In one study, scientists exposed mice to samples of Stachybotrys taken
from homes and looked for immune system responses typical of allergies
as well as inflammation and functional changes in the animals' lungs.
The results showed that the mold can indeed cause a disease similar
to asthma in mice. Meanwhile, other HHRP scientists have developed
sophisticated procedures for identifying Stachybotrys and other molds
in indoor environments, making it possible to determine which molds
are present in a given household. These procedures include methods
for rapidly measuring the amounts of different fungi present in dust and
measuring a biomarker that, when found in a person's blood, indicates
exposure to Stachybotrys. These studies set the stage for further research
that will help determine if humans are responding to the same allergens
as mice and whether these responses can be associated with asthma.
Investigators have also been evaluating strategies for preventing mold
growth. Strategies include applying antifungal sealants for fiberglass and
galvanized steel used in heating and air conditioning systems. Studies
show that sealants can reduce mold growth on fiberglass and can
completely prevent growth on galvanized steel.
REFERENCES:
Environmental Protection Agency, Asthma Research Results Highlights,
EPA 600/R-04/161, Washington, D.C., 2005.
Environmental Protection Agency, Asthma Research Strategy,
EPA 600/R-01/061, Washington, D.C., 2002
Contact. Hillel Koren, Ph.D., EPA's Office of Research and Development,
919-966-9791, Koren.hillel@epa.gov
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Research Shows Effectiveness of
Integrated Pest Management
ISSUE:
Pesticides often are used in large quantities in urban dwellings to
control cockroaches and other pests. However, these chemicals
pose potential health problems to humans, especially children
and expectant mothers. HHRP research has shown Integrated
Pest Management (IPM) to be a safe, effective way to reduce
pest infestation as well as to minimize pesticide exposure,
compared to standard pest control methods. IPM relies on
non-chemical methods, including the cleaning of food residues,
the removal of potential nutrient sources, the sealing of building
cracks and crevices, and the sparing use of minimally toxic
pesticides such as baits and gels.
SCIENCE OBJECTIVE:
HHRP-sponsored researchers investigated whether IPM
techniques and education practices could reduce cockroach
infestation and indoor exposure to pesticides among urban
residents. Following intervention, cockroach levels declined
significantly from baseline levels among households in which IPM
was used. Infestations remained constant in control households.
Additionally, levels of pesticides were found to be significantly
lower in IPM households, but not in control households. These
results show that in this study, not only did IPM lead to a reduction
in infestations, but also in lowered exposure to potentially harmful
chemicals.
Researchers of other HHRP-sponsored studies examined the
effectiveness of IPM practices in urban residences in which
pregnant women lived. Previous studies had shown detectable
levels of chemical pesticides in the urine of pregnant women, as
well as in the blood of their newborns. Further, those newborns
were found to have lowered weight and length at birth, and slower
mental and motor development at age three. Cockroach infestation
levels and pesticide levels in indoor air samples were both sharply
reduced following intervention. Additionally, chemical levels were
detectable in women from a control group, but not from the
intervention group.
APPLICATION AND IMPACT:
Based on the science of these studies and other research
into IPM practices, there has been a movement toward more
widespread use of IPM. New York City, for example, has
enacted legislation that Integrated Pest Management be used
as the preferred method of pest control in all buildings in which
children spend much of the day. The Agency's research on IPM
was used in support of this legislation.
This research effort also is being shared with regional risk
assessors and EPA's Office of Pesticides. The research has
provided the quantitative science needed to gain acceptance in
communities and enabled establishment of regional and national
goals in pest management.
REFERENCES:
Williams, M.K.; Barr, D.B.; An intervention to reduce residential
insecticide exposure during pregnancy among an inner-city cohort,
Environmental Health Perspectives, 2006, doi:10.1289/ehp.9168
(available at http://dx.doi.org/) Online 27 July 2006.
Brenner, B.L.; Markowitz, S., etal., Integrated pest management in an
urban community: A successful partnership for prevention, Environmental
Health Perspectives, Oct. 2003, Volume 111, number 13, pp. 1649-53.
Contact. Nigel A. Fields, MSPH, EPA's Office of Research and
Development, 202-343-9767, fields.nigel@epamail.epa.gov
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TOOLS FOR EVALUATING RISK MANAGEMENT DECISIONS
Researching Trends in Human Health
and the Environment
ISSUE:
Protecting the health of Americans from environmental pollution
is a top priority of EPA. To accomplish this mission, it is clear
that we need to understand the current state of the environment
and how it may be changing over time. HHRP launched an
Environmental Indicators Initiative in 2001 to develop better
indicators that the Agency can use to measure and track the
state of our environment and support improved environmental
decision making. In 2003, the Agency generated the Report on
the Environment (ROE) to describe what is known and what is
not known about the nation's environment. The ROE found that:
• Many studies had demonstrated an association between
environmental exposure and certain diseases and other health
problems, including radon and lung cancer, arsenic and cancer,
and lead and developmental nervous systems disorders.
• Several measures such as life expectancy, the number of
infant deaths, and the major causes of deaths are useful in
assessing health trends over time.
• Measurements of outside pollutant concentrations in air, water,
or land -combined with estimates or measures of frequency
and duration of human exposures to contaminated media
- have provided a valuable foundation for many regulatory and
non-regulatory actions taken by the Agency to limit exposure
to environmental pollutants.
SCIENCE OBJECTIVE:
HHRP is developing the scientific basis for the use of health
outcome measures to evaluate environmental policy decisions
or interventions. It is also developing health indicators that could
provide a clearer understanding of how environmental factors
contribute to public health. Many other factors may also be
linked to the manifestation of disease in addition to exposure to
environmental pollutants, providing a scientific challenge.
APPLICATION AND IMPACT:
HHRP has provided scientific support for the use of outcome
measures such as mortality data to document the success of
major public health programs. For example, research supported
the promulgation of anti-smoking campaigns aimed at males,
which related to a decrease in deaths from lung cancer. Other
research supported the development of biomonitoring data
through the National Health and Nutrition Examination Survey
and other databases, which documented decreases in the
presence of specific environmental agents following regulatory
decisions.
HHRP is conducting research to address the need for more
disease-specific indicators (i.e., cardiovascular, pulmonary, and
reproductive) that can be linked to actual exposure information
at different geographic scales (i.e., local, regional, national)
and to improve understanding of the linkages between source,
exposure, and health effects.
REFERENCES:
2003 Report on the Environment, www.epa.gov/indicators/roe/html
Contact. Denice Shaw, Ph.D., 202-564-3234, shaw.denice@epa.gov or
Danelle T. Lobdell, Ph.D., 919-843-4434, lobdell.danelle@epa.gov. Both
are with EPA's Office of Research and Development.
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Summary of Progress
As illustrated in the previous section in this report, EPA's Human Health Research Program (HHRP) has
made major contributions to a number of problem-driven research areas. HHRP science has contributed to
a more systematic understanding of the physical and biological processes that underlie how humans can be
affected by environmental stressors. We have developed broadly applicable research tools for analyzing and
using information in science-based decision making, and generated methods, models, and data used by risk
assessors and managers to improve the risk assessment process. Other highlights of key accomplishments
for the research program over the last five years include the following:
Biological Research:
• Provided mechanistic information that decreased reliance
on default assumptions used in Agency-related risk
assessments for several chemicals, including atrazine;
arsenic; 1,3 butadiene; bromate; chloroform; chlorpyrifos,-
dichloroacetic acid; dioxin and related chemicals; dimethoate;
and methamidophos. These assessments were published in
databases accessible to the general public, e.g., Integrated
Risk Information System. They are used by Agency program
and regional risk assessors, as well as international human
health advisory bodies (e.g., Organization for Economic
Cooperation and Development, International Program on
Chemical Safety of the World Health Organization) and
governmental groups.
• Developed the Benchmark Dose Software online training
program to evaluate dose-response relationships for
chemicals. This software was made available to the public at,
www.epa.gov/ncea/bmds_training/software/overp.htm.
• Research contributed to the de-listing of ethylene glycol
monobutyl ether and retention of methanol as hazardous
pollutants (OMB PART Review, 2005).
• Research contributed to the revised guidelines for carcinogen
risk assessment, http://cfpub.epa.gov/ncea/cfm/recordisplay.
cfm?deid=l 16283
• Research contributed to the document evaluating the
Reference Dose/Reference Concentration process in risk
assessment, http://cfpub.epa.gov/ncea/raf/RAFRPRTS.
CFM?detype=document&excCol=archive.
• Research contributed to the draft framework for computational
research at ORD, www.epa.gov/comptox/comptox_
framework.html
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Cumulative Risk Research
• Developed models and data to support the cumulative risk
assessment of organophosphate and carbamate pesticides,
www.epa.gov/pesticides/cumulative/common_mech_groups.htm.
• Developed probabilistic exposure model for risk assessment of
chromated copper arsenate (CCA), www.epa.gov/oppad001/
reregistration/cca/.
• Developed a physiologically based pharmacokinetic model to
simulate absorption, storage, metabolism, and elimination of
chemicals in humans, www.epa.gov/heasdweb/erdem/erdem.htm.
• Developed stochastic human exposure and dose simulation
model to predict multimedia, multi-pathway aggregate
exposures for user-specified populations, www.epa.gov/nerl/
research/2003/gl-5.html.
• Provided databases for full and open public access for risk
assessors, including the Technology Transfer Network (www.
epa.gov/ttn/atw/), the Air Pollutants Exposure Model (www.
epa.gov/ttn/fera/human_apex.html), the Consolidated Human
Activity Database (CHAD) (www.epa.gov/chadnetl/), and
the Human Exposure Database System (HEDS),
www.epa.gov/heds/aboutheds.htm
Research contributed to the development of the National
Health Exposure Assessment Survey (NHEXAS), www.epa.
gov/nerl/research/nhexas/nhexas.htm.
Provided analytical methods to support environmental
assessments such as the American Healthy Homes
Survey, www.epa.gov/nerl/news/isea2006/abstract/
healthyhomes_abstract.html
Research contributed to the updates of the Exposure Factors
Handbook, http://cfpub.epa.gov/ncea/cfm/recordisplay.
cfm?deid=12464
Research contributed to drafting the framework for conducting
cumulative risk assessments, http://oaspub.epa.gov/eims/
eimscomm.getfile?p_download_id=36941
Research contributed to characterizing exposures to
toxic agents related to the World Trade Center disaster,
www.epa.gov/wtc/.
Research contributed to developing the Integrated Pest
Management Program for intervention by local health
departments and housing authorities, www.epa.gov/
pesticides/ipm/.
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Research contributed to the development of the
National Agenda for the Environment and the Aging,
www.epa.gov/aging/agenda/index.htm.
Research contributed to the development of
protocols for the National Children's Study (NCS),
www.nationalchildrensstudy.gov.
Research contributed to the drafting of the child-specific
exposure factors handbook, http://fn.cfs.purdue.edu/fsq/
WhatsNew/KidEPA.pdf
Research contributed to the supplemental guidance for
assessing cancer susceptibility from early-life exposure to
carcinogens, http://yosemite.epa.gOV/opa/admpress.nsf/0/
33d8dfc4dfe30aa085256fd3005bdbeb?0pen Document
Research contributed to the writing of the framework for
assessing risks of environmental exposures to children, http://
cf pub.epa.gov/ncea/cfm/recordisplay.cfm?deid=l 16283.
Research contributed to the development of guidance
for selecting appropriate age groups for assessing
childhood exposures.
Research contributed to the characterization of aggregate
exposures of young children to common contaminants in their
everyday surroundings in the Children's Total Exposure to
Persistent Pesticides Study, www.epa.gov/nerl/research/1999/
html/g8-10.html.
Tools for Evaluating Risk
Management Decisions
• Conducted exposure research to determine pesticide levels
in children in border regions between the U.S. and Mexico,
www. nmsu.edu/~frontera/old_1996/nov96/l 196heal.htm.
• Scientists contributed significantly to the Health Chapter
in the Agency's Report on the Environment (RoE),
www.epa.gov/indicators/.
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Future Directions
Major knowledge gaps related to evaluating risk to human health have been outlined by many groups (NRC,
1994; Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997; U.S. EPA,
2005). As described previously, EPA's Human Health Research Program (HHRP) has addressed many of these
gaps and has laid the groundwork for addressing others. Looking ahead, HHRP will sustain its commitment to
this area to ensure that future evaluations of human health risk can be done in a cost-effective manner based
on sound science. Highlights of future efforts include the following:
Biological Research:
PHYSIOLOGICAL MODELS: Risk assessors are often faced with
the uncertainty of relating external exposure to a chemical and
subsequent adverse health effects. HHRP research will develop
integrated physiological models to predict the relationship
between exposure and effect based on available biological data
and extrapolation of knowledge within chemical classes.
METHODS FOR PRIORITIZATION OF CHEMICALS: There are
many chemicals that have not been tested for potential human
health risk. HHRP research will contribute to the development
of a framework for using emerging genomic and proteomic
approaches to prioritize chemicals or chemical classes for
subsequent screening and testing.
BIOLOGICAL MECHANISMS UNDERLYING ADVERSE HUMAN
HEALTH EFFECTS: Recently published guidelines for cancer
risk assessment promote the use of mechanistic or mode-of-
action information in assessing human health risk. Application
of mode of action for non-carcinogenic chemicals also has
been proposed. In addition, HHRP is conducting mode-of-
action research on high priority environmental agents (e.g.,
fungicides, insecticides, endocrine disrupters, air pollutants)
to promote harmonization of cancer and non-cancer
risk assessments.
Cumulative Risk Research:
BIOMARKERS FOR HUMAN HEALTH EXPOSURE AND EFFECTS:
Knowledge of all of the events between exposure to an
environmental agent and subsequent health effect is often
difficult to understand, especially in the context of evaluating
human health risk. HHRP is conducting research to identify
surrogate indicators that are known to change in the same
direction as exposure to environmental agents. EPA will
use valid biomarkers to facilitate assessment of exposure to
multiple chemicals via multiple pathways and to evaluate the
effectiveness of risk management decisions.
Looking ahead, HHRP
sustain its commitment
to this area to ensure
that future evaluations of
human health risk can
be done in a cost-effective
manner based on sound
science.
CUMULATIVE RISK ASSESSMENTS: HHRP conducts cumulative
risk assessments for certain chemical classes, e.g., carbamate
and pyrethroid insecticides as required by Congress.
HHRP conducts research to provide Agency risk assessors
with methods and models for conducting cumulative risk
assessments based on mode-of-action information.
SOURCE-TO-EFFECT MODELS: Knowledge of actual conditions for
all possible exposure scenarios is frequently difficult to obtain,
especially for understanding all possible routes and pathways
for cumulative risk. HHRP will develop source-to-effect models
using stochastic statistical approaches to address ongoing
cumulative risk assessments for environmental agents such as
the carbamate and pyrethroid pesticides.
COMMUNITY RISK: Humans are rarely exposed to a single
environmental stressor. How to evaluate the interaction between
chemical and non-chemical stressors such as nutrition and
other lifestyle factors has not been widely studied, especially as
it relates to risk to populations. HHRP research will identify and
develop exposure assessment methods and models that can be
used for community-based risk assessments.
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Subsceptible Subpopulation Research:
LONG-TERM EFFECTS OF EARLY EXPOSURES: Environmental
factors related to the increased incidence of diseases such
as obesity and diabetes in the U.S. have been proposed,
but not identified. HHRP research will determine the role of
developmental exposure to environmental chemicals and
emerging health risks in adulthood.
SUSCEPTIBLE POPULATIONS: EPA is required to account for the
differential sensitivity of subpopulations in risk assessment. The
scientific basis for identifying and protecting subpopulations
such as children and older individuals, however, is not fully
understood. HHRP research will identify exposure and biological
factors that will help identify who is at greater risk and why and
will promote increased protection of these subpopulations.
ASTHMA IN CHILDREN: The incidence of asthma in children is
increasing rapidly in the U.S. (DHHS, 2001). How changes in the
environment are associated with this observation is not known.
HHRP research will focus on the potential long-term effects of
developmental exposure to air pollutants such as diesel exhaust
and molds and the formation and expression of asthma.
Tools for Evaluating Risk Management
Decisions:
EVALUATION OF RISK MANAGEMENT DECISIONS: EPA currently
uses process-oriented measures of the effectiveness of its
regulatory decisions, e.g., how many smoke-stacks meet
compliance specifications. There is a need to develop more
outcome-oriented means of evaluating effectiveness of its
decisions. For example, do indicators of human health actually
change following a risk management decision? HHRP research
will develop and validate environmental health indicators that
reflect actual impact of risk management decisions on human
health. Such information will help risk managers clarify health
benefits and costs associated with incremental environmental
improvements.
In addition to the research directions highlighted above, HHRP
will rely on directions from cyclical, external peer review by its
Board of Scientific Counselors, input from the Agency's Program
and Regional Offices, and collaborations with EPA's National
Center for Environmental Assessment.
REFERENCES
Clear Air Act, 1990.
www.epa.gov/air/caa/caal03.txt
Department of Health and Human Services. Healthy People 2010, Vol II
(second edition), Chapter 24. Respiratory Diseases, 2001.
www.healthypeople.gov
Federal Insecticide, Fungicide and Rodenticide Act, 1996 (amended)
http://www4.law.cornell.edU/uscode/7/ch6.html
Food Quality Protection Act, 1996.
www.epa.gov/pesticides/regulating/laws/fqpa
National Research Council (NRC). Science and Judgment in Risk
Assessment. National Academy of Sciences, Washington, DC, 1994.
Presidential/Congressional Commission on Risk Assessment and Risk
Management. Final Report. Volume 2, Risk Assessment and Risk
Management in Regulatory Decision-Making, 1997.
Safe Drinking Water Act, 1996.
www.epa.gov/safewater/sdwa/
U.S. Environmental Protection Agency, Supplemental Guidance
for Conducting Health Risk Assessment of Chemical Mixtures,
EPA/600/R-00/062, Washington, DC, 2000.
U.S. Environmental Protection Agency, Draft Report of the Environment,
EPA/600/R-03/050, Washington, D.C., 2003.
U.S. Environmental Protection Agency, Guidelines for Carcinogen Risk
Assessment, EPA/600/P-03/001F, Washington, D.C., 2005.
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United States
Environmental Protection
Agency
Office of Research and Development
Human Health Research Program
Research Triangle Park, NC 27711
Official Business
Penalty for Private Use
$300
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