r/EPA
United States
Environmental Protection
Agency
Proceedings of the U.S. EPA
Workshop on Research Needs
for Community-Based
Risk Assessment
OCTOBER 18-19, 2007
RESEARCH TRIANGLE PARK, NC
-------
U.S. EPA Workshop on Research Needs for Community-Based
Risk Assessment
October 18-19, 2007
Research Triangle Park, NC
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Table of Contents
Session I: Data Needs and Measurement Methods for Community-Based Risk Assessment
Development of Nanoscaled Sensor Systems for Detecting and Monitoring of Environmental
Chemical Agents 1
Desmond Stubbs
Data Collection Platforms for Integrated Longitudinal Surveys of Human
Exposure-Related Behavior 3
Paul N. Kizakevich, Roy W. Whitmore
Elaine Faustman *
Session II: The Biological Impact of Non-Chemical Stressors and Interaction With Other
Environmental Exposures
Social Stress, Stress Hormones, and Neurotoxins
James Herman *
Intersections of Social Ecology, Neurobehavioral Development, and Environmental Contamination 4
Bernard Weiss
Social Environment as a Modifier of Chemical Exposures 5
Robert Wright
Session III: Statistical and Mathematical Modeling for Community-Based Risk Assessment
Louise Ryan *
A Multi-Site Time Series Study of Hospital Admissions and Fine Particles: A Case-Study
for National Public Health Surveillance 6
Francesco Dominici
Risk Assessment/Risk Communication: Understanding the Community 7
Thomas Schlenker
Perspectives, Issues, and Needs in Community-Based Risk Assessment 8
George Bollweg
*Abstract to be provided
Appendices
Agenda
Post-Participants List
Presentations
Summary
The Office of Research and Development's National Center for Environmental Research iii
-------
Session I: Data Needs and Measurement
Methods for Community-Based
Risk Assessment
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Development of Nanoscaled Sensor Systems for Detecting and Monitoring
of Environmental Chemical Agents
Desmond Stubbs
Oak Ridge Center for Advanced Studies, Oak Ridge, TN
Project Objectives: The specific objectives are to design, model, and fabricate highly sensitive, highly
selective, universal sensing arrays for detecting and monitoring personal exposure to a wide range of chemical
agents.
Approach: On October 16, 2006, the Oak Ridge Center for Advanced Studies (ORCAS) hosted a 1-day
meeting that brought together scientists from the U.S. Environmental Protection Agency (EPA), the National
Institute for Environmental Health Sciences (NIEHS), and nanotechnologists to discuss their shared interest in
developing novel nanoscaled analytical instrumentation for a variety of applications, including the
development of personal environmental exposure sensors. The meeting served as a followup to a larger one
held in April 2006 at the EPA campus in Research Triangle Park, NC (see http://orcas.orau.org/
epa/default.htm). EPA and NIEHS investigators were asked to articulate the challenges they encounter as they
relate to identifying, characterizing, and monitoring regulated chemical species in vivo and in situ. A
technology needs assessment analysis was conducted, and the results indicated an urgent need for a rugged,
light-weight, low-cost, wearable, real-time sensor capable of multi-analyte detection with minimal burden to
the individual. The "gold standard" was defined as the ability to simultaneously detect acute as well as
subacute chemical agents with the same sensing system in the field and link this data to a specific biological
event. This type of device would be capable of remote data acquisition, location recording, and control of the
levels and frequency of environmental exposure.
Microfabricated cantilever array platforms pave the way for the development of light-weight, wearable
multi-analyte sensors. Cantilever arrays are capable of the simultaneous detection of multiple analytes, with
extremely high sensitivity, in real- and near-real time. Selectivity, which has been a longstanding problem for
small molecule detection due to the use of unspecific, low-energy receptors, could be achieved by using high-
affinity, high-binding-energy, self assembled monolayers (SAMs)—making the sensor more like a dosimeter.
Unlike other sensors, the low thermal mass of the cantilever allows periodic regeneration by thermal cycling,
achieved by passthrough of electrical current. Selectivity will be enhanced further by integrating three
orthogonal modes into the cantilever platform, namely adsorption-induced cantilever bending, resonance
frequency variation due to mass loading, and differential mechanical calorimetric response. Because inhaled
air should be monitored close to the breathing zone, the sensor will have two units: a passive sensing unit the
size of a pea, including telemetry; and a receiver unit the size of a small PDA, designed to be carried in a
pocket. The PDA unit will have analysis and display capability, and will support global positioning and
biomonitoring device interfaces.
Preliminary Findings and Significance of Findings: Using microelectronic-based arrays, we were able
to detect a number of chemicals of interest in the vapor phase. These include: alcohols , mercury , cocaine ,
and a number of explosives.4 We also were able to conduct proof-of-concept experiments in liquid media
where we successfully detected low levels of bacterial spores in complex media.
Preliminary results suggest that these devices are capable of real-time detection (sub-second scale) of low
vapor pressure chemical compounds in the parts per trillion range.
References:
1. Thundat T, Chen GY, Warmack RJ, Allison DP, and Wachter EA. Vapor detection using resonating
microcantilevers. Analytical Chemistry 1995;67(3):519-21.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
2. Thundat T, Wachter EA, Sharp SL, and Warmack RJ. Detection of mercury vapor using resonating
cantilevers. Applied Physics Letters 1995;66;1695-7.
3. Stubbs DD, Lee SH, and Hunt, WD. Investigation of cocaine plumes using surface acoustic wave
immunoassay sensors. Analytical Chemistry 2003;75:6231-5.
4. Stubbs DD, Lee S-H, Hunt WD. Clues from digital radio regarding biomolecular recognition. IEEE
Transactions on Biomedical Circuits and Systems 2007;l(l):50-55.
5. Lee S-H, Stubbs DD, Hunt WD. Rapid detection of bacterial spores using a quartz crystal microbalance
(QCM) immunoassay. IEEE Sensors Journal 2005;5(4):737-43.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Data Collection Platforms for Integrated Longitudinal Surveys
of Human Exposure-Related Behavior
PaulN. Kizahevich and Roy W. Whitmore
RTI International, Research Triangle Park, NC
Project Goal and Objectives: The goal of this research project is to develop a field platform for
accurately collecting exposure factor data in longitudinal surveys with low enough participant burden that most
people will be willing to participate in week-long studies across each quarter of the year. The objectives are to
develop, validate, and evaluate innovative methods for time/activity/location/exertion-level (TALE) data,
dietary consumption data, and data on use of consumer products, including pesticide products, household
cleaning products, and personal care products.
Approach: A system has been developed that integrates multiple real-time data collection streams and
survey modes on a hand-held pocket PC platform. The system integrates diaries and questionnaires with a
collection of wireless peripheral devices for monitoring physical and physiological data. Three pocket PC diary
modes were studied: interactive menus, voice questionnaires, and passive periodic photos. We also are
investigating innovations such as passive microenvironment identification (i.e., beacons), passive exertion
assessment, wireless product use event markers, wireless interfaces, intelligent prompting, GPS tracking, and
automated daily review to collect the data both accurately and with low participant burden. The system design
emphasizes easy reconfiguration to support varied study requirements, investigator needs, and participant
preferences. A pilot test was conducted in 40 homes to compare participant burden, participant compliance,
data quality, and data collection costs for the pocket PC diaries and paper diary instruments.
Preliminary Findings: To assess burden, the time to use pocket PC menus was monitored and a
debriefing questionnaire was executed. For activity and location, participants averaged 16 and 12 seconds per
entry. Perceived burden for such data were 60 seconds for paper and voice, and 45 seconds for menus. For
cleaning and pesticide questionnaires, participants averaged 52 and 150 seconds per product use. Perceived
burden for cleaning/pesticide data was 60/120 seconds for paper and 60/60 seconds for menu entries. For
dietary data, participants averaged 64 seconds per entry. To assess compliance, the median number of
activities/hour and locations/hour were computed. For activity, these were 1.6/hr (paper), 1.3/hr (menu), 1.2/hr
(voice), and 2.8/hr (photo). For location, these were 1.1/hr (paper), 0.9/hr (menu), 0.7/hr (voice), and 7.2/hr
(photo). Automated room beacons, heart rate monitoring, and GPS data worked fairly well.
Significance of Findings: The burden for menu-based activity and location data entry is good; however,
several participants expressed difficulty with the current TALE menu scheme. Furthermore, some participants
reported avoiding activities and limiting diet to reduce entries for paper, voice, and menu diaries. Participants
liked using the voice diary, although technical issues affected recording quality. Although most liked the photo
diary, some participants expressed privacy issues in their workplace.
Next Steps: We are developing the next generation of the platform, advancing the technology and
focusing on lessons learned during the pilot test. After completing these revisions, we will conduct another
field test in 40-50 homes, and publish the results regarding its performance.
The Office of Research and Development's National Center for Environmental Research
-------
Session II: The Biological Impact of Non-
Chemical Stressors and Interaction With
Other Environmental Exposures
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Intersections of Social Ecology, Neurobehavioral Development,
and Environmental Contamination
Bernard Weiss
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry,
Rochester, NY
Toxic outcomes for neurobehavioral endpoints in risk assessment typically take the form of subtle
functional disturbances, such as lowered scores on neuropsychological tests, rather than blatant pathology. In
addition to the risk assessment difficulties posed by finding sufficiently sensitive and specific measures for
such endpoints, they almost invariably represent a product not just of chemical exposure alone but also of the
social environment in which exposure occurs—the prevailing social ecology. Recognizing that the risks of
adverse effects depend on many factors besides exposure level, investigators have adopted the tactic of
compensating statistically for the influence of the social environment by treating its features as confounders or
covariates external to the primary question of exposure. Socioeconomic status (SES), for example, is typically
assigned the status of a covariate, with the aim of using it to broadly characterize and summarize aspects of the
social environment such as its potential for inducing stress. Treating it as a covariate is designed in essence to
isolate the main effect—toxic exposure. Another different perspective on how the social environment
influences toxic outcomes views its properties not simply as a collection of confounding factors but as
biologically embedded mediators or effect modfiers that have to be treated as elements in a complex causal
nexus. The social ecological setting, through its influence on the vulnerability of the organism to toxic
responses, to some degree determines the biologically effective dose. Examples of this principle can be drawn
from both laboratory experiments and epidemiological investigations. The literature on lead neurotoxicity,
particularly that portion addressing early development, provides a rich source of such examples. Animal
studies have demonstrated how developmental lead exposure can combine with environmental conditions to
either exacerbate or counteract its adverse neurobehavioral consequences. Environmental enrichment, in the
form of group housing and play objects, may attenuate or even eliminate lead's adverse effects while prenatal
or postnatal stress interacts with lead exposure to elicit functional outcomes that depend on combinations of
exposure level, age, and sex. Similarly, epidemiological studies of lead exposure point to SES as a potent
effect modifier, but so far only at a gross level whose critical properties generally fall short of specifics such as
maternal attitudes and behavior. Some of these specifics are traceable, moreover, not only to the individual's
immediate or near environment but also to the wider social setting, which includes factors such as access to
educational opportunities and the incidence of poverty in the surrounding area. Both animal models and
epidemiological investigations must take account of how such socioecological characteristics combine with
toxic exposures to create patterns of human health risks.
Preparation supported by NIEHS grants ESO13247 andESO15509.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Social Environment as a Modifier of Chemical Exposures
Robert Wright
Harvard School of Public Health, Boston, MA
Objective: Psychosocial stressors that correlate with socioeconomic gradients are frequently cited as
potential confounders of the effects of chemical toxicants. New evidence suggests that these factors may
instead synergistically increase chemical toxicity. In this session, the existing evidence for interactions
between psychosocial stress and chemical exposure on neurodevelopment will be presented.
Approach and Preliminary Findings: Data from animal studies demonstrating interactions between
social stressors and neurotoxic chemicals will be reviewed, followed by a review of the research conducted in
human populations. Finally, preliminary results from research on this topic will be presented.
Significance: Because toxic waste sites are associated with poverty, and other social factors that con-
tribute to psychosocial stress at the individual and community level, the toxicity of chemicals found in these
waste sites may be greater per dose than in other communities.
Next Steps: Further research is needed to confirm these results and to potentially incorporate the findings
into risk analysis models for toxic waste sites.
The Office of Research and Development's National Center for Environmental Research
-------
Session III: Statistical and Mathematical
Modeling for Community-Based Risk
Assessment
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
A Multi-Site Time Series Study of Hospital Admissions and Fine Particles:
A Case-Study for National Public Health Surveillance
Francesco Dominici
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University,
Baltimore, MD
At a time when technology enables scientists to conduct research at the cellular and molecular levels of
life and to make extraordinary therapeutic advancements, we remain challenged to translate these new
discoveries into tools to improve the health of populations. Multiple databases are available containing
massive amounts of relevant information on the determinants of health. Research on population health can be
advanced more rapidly by integrating these databases and by designing new mathematical models to identify
and prioritize major threats and their causes. The combination of integrated databases and new analysis tools
comprise a national system for population health research.
We have created a national system for population health research to routinely quantify health risks
associated with short and long-term exposure to particulate matter and ozone. Specifically, a national database
has been assembled comprising time-series data for the period 1999-2005 on daily hospital admission rates for
several cardiovascular and respiratory outcomes, accidents, daily levels of fine particles, temperature and dew
point temperature for the 203 largest U.S. counties. Daily hospital admission rates are constructed from the
National Claims History Files (NCHF) in Medicare. Our study population includes 21 million people,
approximately 60 percent of the total U.S. population older than age 65. Using analytical methodology
developed for multi-site time series studies of air pollution and health, we estimated county-specific, regional,
and national average relative rates of hospital admissions for respiratory and cardiovascular diseases associated
with short-term exposure to fine particles. We also have created Web-based tools for data acquisition,
integration, and dissemination and make these tools accessible to the scientific community to promote a
movement toward reproducible population research.
The pioneering aspect of this work is in the development of a new approach to population health research:
moving from individual epidemiological studies toward an integrative framework that (1) combines
heterogeneous data sources; (2) provides mathematical tools to analyze the assembled information efficiently;
and (3) displays key results to communicate effectively to the public about its health status.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Risk Assessment/Risk Communication: Understanding the Community
Thomas Schlenher
Public-Health Madison-Dane County, Madison, WI
The conceptual model for human health risk assessment based on sources, pathways, routes, populations,
internal disposition, endpoints, and risk metrics (EPA Lead Human Exposure and Health Risk, Volume 1, July
2007) requires, for accurate risk assessment and effective risk communication, a solid understanding of the
communities impacted. Experiences with lead, a well-known toxin, lesser known manganese and previously,
unknown Cryptosporidium illustrate how unique community characteristics inform risk assessment. Likewise,
risk communication must take into account the general community as well as its various segments to be
effective.
The long history, voluminous research, national strategies, and substantial funding associated with lead
poisoning does not obviate the need to establish the sources and pathways of exposure in specific communities
and even households. Prioritizing risk requires engaging the populations most at risk and addressing their
concerns. Internal disposition and physiological endpoints must be understood and explained in human terms.
Risk metrics, when they exist, are of great utility, but often need to be translated to express their practical
value.
Manganese in drinking water only recently has been recognized as a potential toxin (EPA Drinking Water
Health Advisory for Manganese, 2004). Infrastructure to support manganese risk assessment and risk
communication is meager. Local, community-based research may be required to verify sources and pathways.
Special attention must be paid to differentiating the at-risk from the worried well. Indistinct endpoints and
absence of risk metrics place greater responsibility on federal agency/local public health interaction.
Until 400,000 people became ill in Milwaukee in 1993, Cryptosporidium was considered to be a pathogen
only for turkeys (MacKenzie, et al. A massive outbreak in Milwaukee of Cryptosporidium infection
transmitted through the public water supply. New England Journal of Medicine 1994;331(3): 161-7). This
sudden, unprecedented, and widely publicized intoxication of an urban population revealed gaps and synergies
among agencies responsible for public health. The community political process affected both risk assessment
and risk communication. The highly politicized HIV-infected community, being also the highest risk group,
was especially challenged and challenging.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Perspectives, Issues, and Needs in Community-Based Risk Assessment
George Bollweg
Air and Radiation Division, Region 5, U.S. Environmental Protection Agency, Chicago, IL
The term "community-based risk assessment" can broadly apply to human health risk evaluation of
environmental pollutants in specific communities, often with local resident involvement. As community
participants become more involved in scoping, analysis, and characterization of risk, community (host)
characteristics and nonpollutant stressors have received more interest for analytic evaluation. Different
participant roles (e.g., community member, researcher, industry representative, U.S. EPA manager and/or risk
assessor) result in different perspectives on priorities, relevant issues for analysis, what's feasible, and other
issues. Recent experience with specific assessments illustrates several risk assessment and scientific needs.
The Office of Research and Development's National Center for Environmental Research
-------
Appendices
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
October 18-19, 2007
U.S. Environmental Protection Agency
Main Campus, Building C, Auditorium A
Research Triangle Park, NC
AGENDA
Thursday, October 18, 2007
8:45-8:55 a.m. Welcoming Remarks
Hugh Tilson, U.S. Environmental Protection Agency (EPA), National
Program Director for Health
8:55-9:25 a.m. Keynote Address: A Perspective on Community-Based Risk
Assessments
Linda Sheldon, U.S. EPA
9:25-9:45 a.m. Summary of Session: "Exposure Assessment Methods in Community-
Based Risk Assessment" From the International Society of Exposure
Analysis (ISEA) 17th Annual Conference
Brad Schultz, Exposure Modeling Research Branch, EPA
9:45-10:00 a.m. Break
Session I: Data Needs and Measurement Methods for Community-Based Risk Assessment
10:00-10:25 a.m. Development of Nanoscaled Sensor Systems for Detecting and
Monitoring of Environmental Chemical Agents
Desmond Stubbs, Oak Ridge Center for Advanced Studies
10:25-10:50 a.m. Data Collection Platforms for Integrated Longitudinal Surveys of
Human Exposure-Related Behavior
Paul Kizakevich, RTI International
10:50-11:15 a.m. Assessment Methods for Community-Based Risk Assessment
Elaine Faustman, University of Washington
11:15-11:45 a.m. Panel Discussion
11:45-1:00 p.m. Lunch
-------
Thursday, October 18, 2007 (continued)
Session II: The Biological Impact of Non-Chemical Stressors and Interaction With Other
Environmental Exposures
1:00-1:25 p.m.
1:25-1:50 p.m.
1:50-2:15 p.m.
2:15-2:45 p.m.
2:45-3:00 p.m.
Social Stress, Stress Hormones, and Neurotoxins
James Herman, University of Cincinnati
Intersections of Social Ecology, Neurobehavioral Development, and
Environmental Contamination
Bernard Weiss, University of Rochester School of Medicine and Dentistry
Social Environment as a Modifier of Chemical Exposures
Robert Wright, Harvard School of Public Health
Panel Discussion
Break
Session III: Statistical and Mathematical Modeling for Communitv-Based Risk Assessment
3:00-3:25 p.m.
3:25-3:50 p.m.
3:50-4:15 p.m.
4:15-4:45 p.m.
Community-Based Risk Assessment—A Statistician's Perspective
Louise Ryan, Harvard School of Public Health
A Multi-Site Time Series Study of Hospital Admissions and Fine
Particles: A Case-Study for National Public Health Surveillance
Francesca Dominici, Johns Hopkins University Bloomberg School of Public
Health
Risk Assessment/Risk Communication: Understanding the Community
Thomas Schlenker, Public Health Madison-Dane County
Panel Discussion
-------
Friday, October 19, 2007
8:30-9:00 a.m. Perspectives, Issues, and Needs in Community-Based Risk Assessment
George Bollweg, EPA Region 5
9:00-9:15 a.m. Overview of Breakout Groups
Yolanda Sanchez, ASPH Fellow, EPA
9:15-10:45 a.m. Breakout Sessions
10:45-11:15 a.m. Break
11:15-12:15 p.m. Breakout Reports to Group
12:15-12:45 p.m. Closing Remarks
Michael Callahan, EPA Region 6
12:45 p.m. Adjourn
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
October 18-19, 2007
U.S. Environmental Protection Agency
Main Campus, Building C, Auditorium A
Research Triangle Park, NC
FINAL PARTICIPANTS LIST
Beth Anderson
National Institutes of Health
Yolanda Anderson
North Carolina Central University
John Bang
North Carolina Central University
Gary Bangs
U.S. Environmental Protection Agency
Timothy Barzyk
U.S. Environmental Protection Agency
Paloma Beamer
University of Arizona
George Bollweg
U.S. Environmental Protection Agency
Meta Bonner
U.S. Environmental Protection Agency
Margot Brown
ASPH Fellow
U.S. Environmental Protection Agency
Michael Callahan
U.S. Environmental Protection Agency
Jackie Carter
U.S. Environmental Protection Agency
Teresa Chahine
Harvard School of Public Health
Annie Chaisson
The LifeLine Group
Jason Ching
U.S. Environmental Protection Agency
Kathryn Conlon
ASPH Fellow
U.S. Environmental Protection Agency
Kacee Deener
U.S. Environmental Protection Agency
Peter deFur
Virginia Commonwealth University
Saundra DeLauder
North Carolina Central University
Francesca Dominici
Johns Hopkins University
Christie Drew
National Institutes of Health
Mari Eggers
Montana State University at Bozeman
Lena Epps-Price
U.S. Environmental Protection Agency
Elaine Faustman
University of Washington
Alesia Ferguson
University of Arkansas for Medical Sciences
-------
Nigel Fields
U.S. Environmental Protection Agency
Roy Fortmann
U.S. Environmental Protection Agency
Natalie Freeman
University of Florida
Kim Gray
National Institutes of Health
Davyda Hammond
U.S. Environmental Protection Agency
Shirley Harder
U.S. Environmental Protection Agency
Chris Heaney
University of North Carolina at Chapel Hill
James Herman
University of Cincinnati
Ross Highsmith
U.S. Environmental Protection Agency
Chih-yang Hu
Louisiana State University
Elaine Cohen Hubal
U.S. Environmental Protection Agency
Robert Hubal
RTI International
Janis Johnston
AAAS Science and Technology Policy Fellow
U.S. Environmental Protection Agency
Paul Kizakevich
RTI International
Carrie Knowlton
ASPH Fellow
U.S. Environmental Protection Agency
Matthew Lakin
U.S. Environmental Protection Agency
Jonathan Levy
Harvard School of Public Health
Debbie Lowe Liang
U.S. Environmental Protection Agency
Danelle Lobdell
U.S. Environmental Protection Agency
Robert MacPhail
U.S. Environmental Protection Agency
Qingyu Meng
U.S. Environmental Protection Agency
Lynne Messer
U.S. Environmental Protection Agency
Jayne Michaud
U.S. Environmental Protection Agency
Ginger Moser
U.S. Environmental Protection Agency
Eloise Mulford
U.S. Environmental Protection Agency
Pasky Pascual
U.S. Environmental Protection Agency
Peter Preuss
U.S. Environmental Protection Agency
James Rabinowitz
U.S. Environmental Protection Agency
Pamela Rao
Farmworker Justice
Ravishankar Rao
U.S. Environmental Protection Agency
David Reif
U.S. Environmental Protection Agency
Larry Reiter
U.S. Environmental Protection Agency
Tonesia Rouse
U.S. Environmental Protection Agency
Louise Ryan
Harvard School of Public Health
Elizabeth Sams
U.S. Environmental Protection Agency
-------
Yolanda Sanchez
ASPH Fellow
U.S. Environmental Protection Agency
Thomas Schlenker
Public Health Madison-Dane County
Dina Schreinemachers
U.S. Environmental Protection Agency
Brad Schultz
U.S. Environmental Protection Agency
Deborah Segal
U.S. Environmental Protection Agency
Linda Sheldon
U.S. Environmental Protection Agency
Matt Shipman
Risk Policy Report
Amar Singh
Lockheed Martin (Contractor)
Gene Stroup
U.S. Environmental Protection Agency
Desmond Stubbs
Oak Ridge Center for Advanced Studies
Kathy Sykes
U.S. Environmental Protection Agency
Kent Thomas
U.S. Environmental Protection Agency
Hugh Tilson
U.S. Environmental Protection Agency
Julie Jacobson Vann
University of North Carolina at Chapel Hill
Winona Victery
U.S. Environmental Protection Agency
Ingrid Ward
U.S. Environmental Protection Agency
Timothy Watkins
U.S. Environmental Protection Agency
Bernard Weiss
University of Rochester
Sharon Wells
U.S. Environmental Protection Agency
Deb Wesley
Roy Whitmore
RTI International
Richard Wiggins
U.S. Environmental Protection Agency
Ann Williams
U.S. Environmental Protection Agency
Sacoby Wilson
University of South Carolina
Michael Wright
U.S. Environmental Protection Agency
Robert Wright
Harvard School of Public Health
Valerie Zartarian
U.S. Environmental Protection Agency
Contractor Support
Mary Compton
The Scientific Consulting Group, Inc.
Jen Hurlburt
The Scientific Consulting Group, Inc.
Kristen LeBaron
The Scientific Consulting Group, Inc.
Maria Smith
The Scientific Consulting Group, Inc.
Mary Spock
The Scientific Consulting Group, Inc.
-------
HUMAN HEALTH RESEARCH PROGRAM
Workshop on Research Needs for Community-
Based Risk Assessment
October 18-19, 2007
HUGH A. TILSON
National Program Director
Human Health Research Program
Office of Research and Development
ORD PROGRAMS INVOLVING
HUMAN HEALTH
Human Health Research Program
Human Health Risk Assessment
Participate Matter
Air Toxics
Drinking Water
Endocrine Disrupters
Safe Pesticides/Safe Products
Homeland Security
HUMAN HEALTH RESEARCH
HUMAN HEALTH RESEARCH PROGRAM
The main objective of the Human Health Research
Program is to reduce uncertainties associated with the
risk assessment process by providing a greater
understanding of exposures to environmental
stressors and the basic biological changes that follow
Four Long-Term Goals of the
Human Health Research Program
Long-Term Goal 1:
• Risk assessors/managers use ORD's methods, models and data to
reduce uncertainty in risk assessment using mechanistic (or mode of
action) information
Long-Term Goal 2:
• Risk assessors/managers use ORD's methods, models and data to
characterize aggregate and cumulative risk assessment
Long-Term Goal 3:
• Risk assessors/managers use ORD's methods, models and data to
characterize and provide adequate protection for susceptible
subpopulations
Long-Term Goal 4:
• Risk Assessors/managers use ORD's methods and models to
evaluate risk management decisions
Scientific Questions Driving
Research on Cumulative Risk
What biomarkers are available to improve
cumulative risk assessments?
What exposure models are available that can
estimate aggregate exposures and cumulative
risk?
How can mode of action and exposure
information be used to conduct cumulative risk
assessments?
How can cumulative risk be assessed at the
community level?
Research on Community Risk
Develop tools and framework to assess
interaction of environmental chemical and non-
chemical stressors at the community level
Research on assessing exposure and health risk
of tribes due to cultural practices
Evaluate tools for use in assessing community
risk
• Regional demonstration studies
• Community action for a renewed environment
• National Children's Study
-------
A Perspective on Communit
Based Risk Assessments
Linda Sheldon
Associate Director for Human Health
National Exposure Research Laboratory
Fundamental Concepts
Not all communities are the same
Different communities can have
differential risks due to exposure
to environmental contaminants
and other stressors
The same community can have
differential risks over time
Fundamental Concepts
Many of EPA's regulations do not consider
these differences
• NAAQS
• FQPA
However there are many communities that
may be at higher risks because they are not
adequately protected through
• Environmental regulations
• The distribution of social benefits
Not a new concept
Fundamental Concept
Cumulative Risk: The combined risks from
aggregate exposures to multiple agents or stressors.
Cumulative risk assessment: An analysis,
characterization, and possible quantification of the
combined risks to health or the environment from
multiple agents or stressors.
.Source: Framework for Cumulative Risk
Assessment, 2003
Questions
How do we identify the most
important risks in these
communities?
How do we assess the cumulative
risk in these communities?
How do we develop appropriate
risk mitigation procedures?
My Perspectives on this Issue
Developed during the past
• 3 to 4 years
• 3 to 4 months
• 3 to 4 days
-------
Past 3 to 4 years
NERL research program in
Aggregate Risk
How to extend to cumulative risk
• Not just going from one to mixtures of
chemicals, but
• Needed to consider multiple stressors
• Must consider the community to do
this
Past 3 to 4 Months
Introduced to Ecological Research
Ecologists are always considering
• Communities- i.e., ecosystems
• The entire range of stressors and
cascading effects
They have developed models and CIS
tools that should be applicable here
We should learn from the ecologist
Past 3 to 4 Days
ISEA meeting -
• Application of advanced statistical, GIS, and
modeling tools to understand exposure and risk
• Marie Lynn Miranda- lead and air toxics
• Marc Serre - water contamination, CAFO
• Must consider concerns of the community and
work with the community
• Need for tools to use at the community level
• Need to Develop Partnerships for community
work-CARE Program
So, what is needed
Science
Tools
Communication
Partnerships
Trust
Building the Science
Environmental
Release
Adverse
Outcome
Early Biological
Concentrations 11 Exposure II Target Organ 11 Effects
Concentrations 11 Dose
This is the "core" research that we are
conducting to determine exposure and
health risks
-------
Building the Tools
This should be the emphasis
• Simple easy low cost monitoring
methods
• CIS tools
• Models for exposure
• Comparative data bases
• Tools for interpretation
• Primers for conducting assessments and
using the tools
Communication
As scientists, we need to keep it simple
"Working toward Duh"
Listen to the community
• Hear their concerns
• Know that they are different and how this
impacts their risk
Describe the science
• The issues
• What we know
• What we can do to change it
• What else we know that can help the community
All researchers must be
involved with the community
at some level
Paradigm shifts
For Agency: From decision-maker
to providing technical assistance
to help communities make
decisions
For Exposure and risk analysis:
From analysis done for
community to partnering in a
deliberative process
Summary
• This is important-we have an
opportunity to make a difference
• This is hard work
• Multidisciplinary
• Communities must be involved
• Impact is important
• We have the technology to do it and that
will keep improving
• We just need learn how to put it together
That's what this workshop is about
THANK YOU!
-------
Report from
tsure
Science for Community-base*
Cumulative Risk Assessment
B. Schultz
V. G. Zartarian, session co-chair
U.S. EPA Office of Research and Development
National Exposure Research Laboratory
ORD/NCER, ORD/NCCT Planning Meeting
October 18, 2007
Brief Overview
CARE overview by CARE co-chair
• Coordinates EPA Program & Regional
offices
• Supplements EPA regulations
• Coordinated with CDC; Moll, joint efforts
• To support community-driven risk
assessment & risk management
CARE Level 1: risk
ranking/prioritization & selection of risk
reduction activities
CARE L2: risk reduction (& quantifying
effects)
Overview (cont'd)
CARE technical issues overview by
environmental health assessment co-
chair
Region 1 (New England) case studies
Region 6 cases & status of EPA
cumulative assessment guidance
EPA lead on NCS gave NCS overview
• Basic science info, on the environmental
exposures related to health effects
• Both individually & in combination with
other chemical exposures & non-chemical
stressors
Overview (cont'd)
NERL PI on research program
• Exposure tools research
• Collaborate with health scientists, risk
assessors, CARE program (L1 & L2)
• Many exposures - focus on exposures
leading to highest risk and most in
demand by communities
• NCS exposure assessment research
• Chemical stressor primary expertise
Summary of some NERL activities
• Survey of CARE POs for needs
• Measurement methods research
• Modeling research
immunity Needs & Research Needs \
for Community-based Cumulative
Risk Assessment
• Community monitoring/low cost techniques INERLSNCERI
Is the action having an impact on health? INCER>
What does monitoring mean, once we do it?
What do modeling results mean?
• How to get community involved: relationship between
exposure and health? Local partnerships.
• Communities need someone who understands
•Need to include local conditions, often only visible in person
•Need to include local values
Non-chemical stressors and vulnerability INCER>
Guidance for choosing appropriate methods for
measurement collection
Research needs (cont'd)
• Better ways to quantify local non-chemical
information: lifestyle; access to health care;
exposure to violence
• Inventories/protocols for assessing non-
chemical stressors as well as chemical
stressors
• Tools to characterize dietary exposures at
community level (diet, sources of food, food
preparation, storage) for unique cultural
groups
1 Simple, user-friendly tools to
characterize/translate/use sources/emissions
to assess risk and risk reduction scenarios
(e.g., simplified version of RAIMI)
• Documentation on how to select models
• Documentation on how to use models
-------
Research needs (cont'd)
• Models that start at local/neighborhood level
• Better local source identification/emissions
inventories in the community; tools to
facilitate that (e.g., GPS; checklists)
• Quantify benefits so that other
communities can apply findings
• Note: 1000s of communities & communitv-
* driven assessments
Research should be directly usable by
community or their local health or
environmental department
• EPA cannot serve every community individually
• States may not be able to serve every community
individually
Summary
Community-driven assessment of importance
Research needs to be usable by communities/local
health depts.
Cumulative risk important
• Including non-chemical stressors, vulnerability
Focus on main contributors to risk/health impact to
address cumulative risk
Also, focus on recurring community Qs
Non-chemical stressors: less in-house expertise
Protocols for non-chemical stressors needed
Low-cost measurements important
Dose-response for risk prioritization important
• Comparison with other chemical risks
• Comparison with non-chemical stressors
Quantifying benefits important for future applications
by communities
Objectives
1) To develop tools for estimating human exposures
to multiple chemical stressors that are most
likely to impact cumulative risks.
2) To apply, evaluate, and demonstrate these
exposure tools through selected community
case studies.
3) To communicate research findings and provide
the tools to stakeholders.
Approach
> Identify partners, stakeholders, research needs
> Collaborate with partners who are focusing on
other components of human health source-to-
outcomes paradigm
source->concentration->exposure->dose->risk->outcomes
I > Develop exposure tools to address science
questions
I > Identify initial case studies for collaboration
I> Evaluate, apply, demonstrate tools through case
studies
> Communicate research and provide tools
Potential Partners/Stakeholders
EPA Community Action for a Renewed Environment (CARE)
program partners (e.g., EPA regional offices, state and city
agencies, community groups)
EPA Cross Program Project Teams (e.g., CARE, accountability,
environmental justice, urban environments, tribal)
Regional risk assessors
National Children's Study, Vanguard Centers, future Centers
Researchers in ORD labs/centers
EPA program office risk assessors/managers
Other EPA Groups (e.g., OEI, OEJ; RAF; OCHP)
Academia
Other federal agencies (e.g., CDC, NIEHS)
Science Questions
1) How to systematically identify and prioritize key
chemical stressors within a given community?
2) How to develop individual estimates of
exposure to multiple stressors for epi studies?
3) How to use exposure tools to assess
community level distributions of exposures:
a. to develop and evaluate the effectiveness of
risk management/mitigation strategies?
b. to provide better links between reduction
actions, exposures, risks, and outcomes?
-------
Science Question #1 - Overview
Rationale
• research planning
• systematic approach for community
assessments
• guidance for collecting community information
Stakeholders
• ORD/NERL, EPA CARE program and Level I
projects for tools review tables
• EPA CARE, Region 4 and OEI for CARE
questionnaire data
• EPA Region 5/CARE for Detroit exposure
modeling
y^J^L'J'JJ.II
I Science Question #1- Planned Tools
'' • Summary of relevant programs, guidance,
research needs
Summary tables for models, data, and methods, to
enhance CARE Community Screening Workbook
• Models: fate/transport, exposure, dose, risk
• Methods: community level, individual level, under
development
• Data: biomarkers, outdoor air, indoor air, UV, drinking
water, house dust/residues, food
Quantitative community level 4-model comparison
with Detroit case study
EPA CARE program survey results
Detroit CARE Level I Case Study
> Identify and prioritize cumulative air toxic sources in
the community and seek ways to reduce exposure
and risks
> Initial meetings between NERL leads and Region 5
CARE Project Officers
> Gathering available information
> Exposure model comparison with Detroit case study
> Planned GIS mapping of emissions, concentrations,
and exposures
Science Question #2 - Overview
Rationale
Need exposure tools to support the National Children's
Study (NCS)
Need refined tools for individual-level exposures to
multiple "agents" overtime in epidemiological studies
Stakeholders
NCS, specific Study Centers and communities, academia
Status
Review of NCS Research Plan -identified role for models;
needs for methods and approaches
Initial efforts to identify potential case studies
Science Question #2 - Potential Case Studies
> Air pollution
• Community-level air measurements
• Relate to ambient measurements and models
> Diet
• Community dietary measurements
• Questionnaire and checklist to identify unique
dietary patterns and food consumption
> Multimedia exposure and dose assessment
Relate to biological measurements and models
(e.g., for Arsenic)
Science Question #2 - Planned Tools
Methodology, strategies & guidelines for
epidemiological study-related measurement
collection, e.g.,
Biomonitoring and interpretation
Environmental methods
Model inputs and evaluation
Exposure field study designs
Dietary exposure model for individuals
Cumulative inhalation model(s) forepi studies
Cumulative multimedia model(s) forepi studies
-------
Science Question #3 - Overview
Rationale
Exposure tools needed to refine risk assessments
Planned Tools
• Linkage of refined tools for emissions, concentrations,
and exposures for community risk assessments
• New methods for continuous monitoring of multiple
pollutants in communities
• Cumulative community inhalation exposure model(s)
• GIS tools for illustrating reduction scenarios
• Approaches for area source risk assessments
Stakeholders
• CARE program, Regions, ORD labs/centers, Program
Offices (e.g., OAQPS, OPPT), CDC
MMWVwd
•j^/lL'J'J^.n
•
2006 Boston CARE (Level II) Case Study
2-year risk-reduction project (BPHC Safe Shops)
Regulatory and community focus on auto shops;
EPA/CDC pilot study
600 shops clustered in diverse, low-income
neighborhoods
Goal: measurably reduce negative environmental
and public health impacts by auto shops on
workers and residents by reducing emissions
Current tools to measure results are surveys for
changes in best practices and pollution prevention
CARE lead has requested ORD assistance to help
quantify impacts of program; enhance science
Boston CARE: Progress
7/07 Meeting to discuss EPA auto shop efforts
> NESHAP auto body area source rule
> OAQPS Collision Repair Campaign
> OPPT DfE Auto Body Program
> CARE Program (Boston Safe Shops, others)
> Lawrence, MA RARE auto body project
8/07: cross-ORD meeting to discuss project support
Meetings between ORD/NERL and stakeholders
Research on available studies and tools to assess
cumulative risk from auto shops
> Drafting ORD research plan to be finalized and
shared with collaborators, stakeholders
BwwTwrH
• . •, ••;,,•
EPA/ORD/NERL
immunities Project Timeline
Develop tools to assess community risk
Project Research Plan
Review of available tools (models, methods,
data, approaches) for community-focused
cumulative risk assessments
Apply tools to assess community risk
Develop and apply exposure tools to help
communities and to enhance science related to
community cumulative risk assessments
Provide tools to stakeholders and demonstrate
tools' utility through selected case study
applications
2009
2008
2008
2011
2010
2011
Expected Results/Benefits
Research outputs to
"Facilitate identification of environmental stressors that pose
an unreasonable risk to human populations,
| > Reduce exposure of humans to multiple environmental
stressors through multiple pathways,
| > Reduce exposure of populations at risk to environmental
stressors, and
| > Improve effectiveness of risk management decisions"
(EPA/ORD Human Health Multi-Year Plan, p. 14)
• Exposure assessment tools to address project goals,
objectives, science questions
• Effective transfer and communication of research and
tools through published results and presentations
Disclaimer
Although this work was reviewed, by
EPA and approved for presentation
and publication, it may not
necessarily reflect official Agency
policy.
4
-------
1/29/2008
Nanoscaled, microelectronic sensor
systems for detecting and monitoring of
environmental chemical agents
By Desmond Stubbs
Presented to:
Community-Based Risk Assessment
Workshop
October 18,2007
Where did rj come from?
eras
I + ORAU = UT-BATTELLE
The Mission...
ORCAS is a think and do consortium of research universities,
government, industry, and non-governmental organizations.
It is focused on critical issues with strong science and technology
content.
Problems are framed broadly, taking into account their scientific,
technical, economic, social, and policy dimensions to develop
research and integrated strategies for addressing those challenges.
We attempt to ensure that our ideas and research are translated into
action.
April 2006 Workshop...
Nanotechnology Applications in Environmental Health: Big Plans
for Little Particles
•Introduction of two research communities
- Nanomaterials/nanosensors
- Environmental health/ecological health
•Exploration of the "art of the doable" on the nano-side
•Discussion of the possible environmental health effects, exposure
assessment and ecological health applications
•Better informed communities with likelihood of beneficial
interactions in the future
The Case for Nanotechnology - Commentary by Michael Strano
(Asst. Professor,
University of Illinois- Urbana)
•It has been pointed out that generally the detection limit of a sensor scale
approximates the cube of its characteristic length. So smaller sensor elements
mean lower detection limits generally.
•The case varies both with the type of material used in its design and the
physical and chemical properties of that material.
•Fluorescence-based techniques are some of the most powerful molecular
detection methods available. Single molecule fluorescence analysis is a now
routine. For optical fluorescence-based sensors, there are classes of
nanoparticlesthat exhibit extremely enhanced photostability in fluorescent
emission. This means that for the first time new types of sensors can be
devised with extremely long operational lifetimes. This is not possible with
conventional fluorophores (e.g., single-walled carbon nanotubes are infinitely
photostable at moderate lightfluxes).
•Some nanosystems emit light at longer wavelengths where few conventional
materials operate whereas few conventional materials do so. The human body
is particularly transparent to near-infrared light in a narrow region of the
electromagnetic spectrum. These systems will form the basis of novel detection
technologies that can operate in strongly scattering media where fluorescent
spectroscopy is limited.
•Nanoparticles can also possess features that are commensurate with
biomolecules and other important macromolecular analytes. Electrodes that are
narrow enough to fit or conform to biological structures should be capable of
transducing subtle changes in these structures,
The Case for Nanotechnology - Sensor shelf-life,
Real-time detection, Useful life
•Shelf Life-varies as a function of the sensing layer. For example,
bioreceptors (antibodies, enzymes, lipid layers) are limiting factors
because of their inherent short life span under non physiological
conditions. On the other hand, aptamer- and polymer-based sensing
layers have been used in an effort to extend the lifetime of the device.
•Real-time Detection - is a common feature of nanosensing technology.
The nanosensors described in the meeting all operated on a time scale
ranging from seconds to minutes.
•Useful life - The binding mechanisms for the sensor platform can be
described as reversible—requiring little or no surface treatment to return
the sensor to its steady state—or irreversible where analyte binds with
high affinity such that surface treatment is required to remove the bound
substrate.
-------
1/29/2008
Emerging Technologies in Exposure
Assessment
Microelectromagnetic Sensor
Interferometric Optical Sensor
Vapor phase sensor system
Flow cell and oscillator circuit
Gas in \ *Gas out
Principle of Operation
Principle of Operation
Antibody Immobilization on Au
Electrodes
Courtesy Sang Hun Lee
-------
1/29/2008
Multi-Analyte Detection - Arrays
Arrays of sensors on a
single chip with
selective coatings for
application-specific
programmable sensors
Arrays give more
information than
separate sensors
Coupled to custom
readout electronics
Telemetry
Mass production
Inexpensive
(Array continues
in both directions)
Coating #1
Coating #2
Implanted Behind Neck in WiStar
Rats to Measure Ethanol Levels
Rats Injected with
Oneg/KgofEth
Body Temperature
& Eth Monitored
For Several Hours
Data from
Interstitial Fluid
Tracked Blood Lvl
Testing in WiStar Rals At
Dr. William McBride's La
At Indiana I . Indianapolis
Why TNT?
2,4,6-Trinitrotoluene (TNT)
Low vapor pressure ~ 1.99x 10~4Torr
Ability to detect trace levels of TNT is key to:
•Reducing fatalities from land mines (TNT constitutes 80% of all land
mines -there are over 100 million scattered across the planet)
•Tracking explosives materials (Anti-terrorism)
•Environmental concerns (water and soil contamination)
TNT Analogs
Musk Oil (Musk Xylene)
TNT
Ammonium nitrate
\/\ =0
/ \ /
TNT Analogs
-------
1/29/2008
Questions?
-------
Data Collection Platforms for Integrated Longitudinal
Surveys of Human Exposure-Related Behavior
EPA STAR Grant RD-S31541-01
Principal Investigators:
Roy Whitmore, Ph.D., Statistician
Paul Kizakevich, M.S., BiomedicalEngineer
Paul Kizakevkh, presenting
3040 Cornwallis Road
Phone 919-541-5809
P.O. Box 12194 Research Triangle Park, North Carolina, USA 27709
Fax 919-541-5966 " e-mail kiz@rti.org
feed for Integrated Data Collection
Routes of exposure
Inhalation
Ingestion
Dermal contact
Modifiers of exposure
Breathing rate, exertion, specific activities
Food and beverage consumption
Use of consumer products
Carpet, gloves, open doors/windows, microenvironment)
Season, geographical location, temperature, humidity
Overall Objectives
Develop a personal data collection system that:
integrates data input streams for collection of human exposure-
related behaviors
supports EPA human exposure assessment models
is easily adapted for other human exposure assessment studies
• has sufficiently low burden that most members of the general
household population of the U.S. will be willing to participate in
the study for at least 1 week per season for 1 year
Approach
Develop diary methodologies for data collection
Develop sensors & automation to reduce burden
Evaluate methods in the general population
Assess, improve, and enhance developments
Re-evaluate methods and technologies
Facilitate system use for other research studies
Paper diary -traditional forms and booklets
Menu diary -menus and forms on Pocket PC (PPG)
Voice diary - questions/answers on PPG
Photo diary - periodic photos on PPG
Automation
« GPS for outdoor location and movement
* Wireless beacons for indoor residential locations
• Wireless Polar chest belt for heart rate monitoring
• Accelerometers for movement and compliance monitoring
- KTI
Paper diary -formsand booklets (24-hour recall)
Menu diary - menus and forms on PPG (real-time)
Voice diary - questions/answers on PPG (real-time)
Automation - none
-------
Methods
Consumer Product Data Collection
Paper diary -forms and booklets (24-hour recall)
Menu diary -menus and forms on PPC (real-time)
Automation -wireless buttons record each product use event
Personal care products
• Soaps and shampoos
" Fob-initiated time stamp
Household cleaning products
• Kitchen and bathroom cleaners and sanitizers
• Fob-initiated time stamp; then Pocket PC forms/questionnaire
Pesticide products
a Fob-initiated time stamp; Pocket PC-based forms/questionnaire
• Aerosols weighed before and after use; weights sent wirelessly to PPC
'ersonal Data Collection Platform
Pocket PC Menu Diaries
12
12
§2
Multilevel menus are used to capture activity and location data.
Familiar navigation style to
facilitate user interaction
Multilevel menus are used to capture dietary data, with radio-buttons for serving size
A sequence of questionnaire forms are presented in response to a pesticide fob event
120° lens Pocket PC Image Censoring & Analysis
-------
Headset/Fob
Pocket PC
Activity / Location / Diet Coding
Locator Beacons
Beacons are placed throughout the residence in
study-designated rooms
Each beacon is configured for:
Maximum detection range for designated room
Study detection interval (e.g., 60 seconds)
Beacon ID code for room identification
Designated Pocket PC Bluetooth address
Location tracking:
At each interval, the beacon microcomputer
powers up the internal Bluetooth module
The beacon attempts to establish a Bluetooth
connection with the designated Pocket PC
If a connection is established, the beacon
sends a time/date stamped Beacon ID code to
the Pocket PC
The internal Bluetooth module is powered
down until the next interval
Bluetooth
Beacon
sample Residential Beacon Use
Jilot Evaluation of Technologies
Purpose:
• Evaluate technical performance of technologies & systems
'= Evaluate participants, analyst burden for various diary modes
Participants (N=48)
• Gender: Female (N=35); Male (N=13)
• Age: 18-34 (N=14); 35-65 (N=25); >64 (N=9)
• Ed: HS/GED (N=14); some college (N=16); college grad. (N=18)
Field study design
* Four data collection modes: Paper, PPC menu, PPC voice, PPC photo
* All had heart rate and residential location beacon monitoring
" All use wireless fobs to record product use events
* Each participants used the data collection system for 7 days
Activity
/Dressing
/Sort/Iron Clothes
dotor Vehicle
nking
/Putting Away Items
d Paperwork
:>r Resting
/Putting Away Items
Food
TV
shing
-
Time
17:01:43
18:05:59
18:05:59
18:03:02
18:03:02
18:03:02
13:06:20
13:06:20
21:59:52
13:15:03
13:15:03
17:51:26
17:51:26
Food / Beverage
Tea
Cheese (plain or as part of dish)
Crackers, any kind
Beef or veal
Potatoes, any other
Other salad
Nuts (peanuts, etc.)
Coffee
Tea
Banana
Chicken, turkey or other poultry
Beans, green
Potatoes, any other
fc'RTI
RTI
-------
Participant reporting compliance
Diary
Mode
Paper
PPC
Voice
Photo
Activities
per hour
1.42
1.12
1.29
2.69
Locations
per hour
0.95
0.75
1.34
2.59
Top 1 5 activities reported by mode
_
Activity
Riding in Motor Vehicle
Eating/Drinking
Non-strenuous Work
Sleeping
Watching TV
Walking
Grooming/Dressing
Visiting with Others
Picking up/Putting Away Items
Preparing Food
Tub Bath
Relaxing or Resting
Reading/Writing
Using Computer
Moderately. Strenuous Work
PPC
<%>
23.0
11.7
8.1
6.2
5.6
3.8
3.6
2.7
2.5
2.5
2.5
2.2
2.1
2.0
1.6
Paper
(%)
22.4
8.4
8.2
4.2
4.5
6.5
5.0
1.0
1.3
3.9
0.1
2.0
2.1
1.6
0.1
Voice
<%>
21.9
5.9
7.8
2.9
4.9
8.0
2.4
1.0
0.9
4.9
0.0
3.4
1.2
1.2
1.4
Photo
(%)
16.2
3.2
4.4
0.0
9.2
17.6
4.1
5.8
2.4
5.8
0.0
2.8
1.8
3.2
0.00
RTI
DaT?JT
Ell
•
ntry Burden (median)
o complete entry in seconds
Act/Loc/Environ
• Activity
• Location
• Combustion
• Smoking
• Windows/doors
Cleaning products
Pesticides
Measured
Menu
28
11
9
1
3
4
36
131
Perceived
Menu Voice Paper
45 60 60
60 n/a 60
60 n/a 120
ftfen for each entry of an activity/location and for each product use questionnaire
P KRTI
Data Coding Burden (median)
Menu1
Photo2
Voice2
Paper3
Analyst
hours
00.0
58.5
87.4
69.7
Study
hours
630.1
282.4
427.0
979.7
Analyst hours
per 24-hr day
0.00
4.97
4.91
1.71
1. Pocket PC menu diary is self-coded by the participant
2. Time for coding by a single analyst.
3. Included time for 100% re-key verification.
Paper
food item
Bottled water
Other grain
product
Chick en, turkey or
other poultry
Potatoes, any
other
Paper
PPC
food item
Soft drink (soda,
cola, etc.)
Chicken, turkey or
other poultry
Chocolate/ candy
Juice mixtures
Lettuce salad with
assorted vegs.
Other sweets or
dessert
Voice
food item
Bottled water
Chicken, turkey or
other poultry
Other grain
product
Rice and rice
mixtures
Other non-
alcoholic drink
4.7
4.2
ijRTI
Conclusions
The burden for menu-based activity and location data entry is low;
however several expressed difficulty with the menus.
Activity and location reporting was lower than in previous studies.
Participants liked using the voice diary, although technical issues
affected recording quality.
While most liked the photo diary, some participants expressed privacy
issues in their workplace.
Some participants reported avoiding activities and limiting diet to
reduce entries for paper, voice, and menu diaries
Further improvement in menu structures, prompting, and automation
may help to improve compliance and avoid behavior modifications
-------
Assessment Methods for Community
Based Risk Assessment
Elaine M. Faustman, Ph.D.
Three types of studies were examined
in order to understand what pesticide
exposures were occurring in children
1. Community Based Participatory Research
project (CBPR)
2. Longitudinal multiple sampling project aimed at
understanding between and within family
variability
3. Longitudinal Cohort Study
Estimated Organophosphate and Carbamate Usage
on Apples and Potatoes in Washington State, 2001
Study Counties for the Center for Child
Environmental Health Risks Research
Examples of Chemicals Applied to
Washington State Crops, 2001
Chemical class
Poundsapplied
Organophosp hates
N-Me Carbarn ates
DJihiocartJamate
Apples | Azinphos-methyi:
: CnScroynibs :
I Phosmet ]
HOtrLoei,; Err-op'-op ;
; iVietoniMiophoi ;
Ap^Ks ; cy/boryl :
Potatoes; Aifjcait- :;
App.es ; Ma:;COZeD ;:
i::ioi'?;k^s ! Ivlancozeb I
241 000 ::
23TCOC ;
"""""i38;o66""""" ;
119,000 ;
143IOOO :
202! 000 :
153,000 ::
82"obO ;
3^xbW"""""""""1!
Source: "Agricultural Chemical Usage (PCU-BB)" National Agricultural Statistics Service
Agricultural Statistics Board, U.S. Department of Agriculture
(http://jan.mannlib.cornell.edu/reports/nassr/other/pcubbAccessed 05/03)
The Take-home Pathway for Agricultural
Pesticides: Contributions of Occupational
Factors to Home Contamination
G.C. Coronado, I. Islas, S.A. Snipes,
J. Grossman, and B. Thompson
-------
Communities in
• Community was defined as
either a town or a labor
camp
• Pairing of an intervention
community with a control
community was performed
separately for towns and
labor camps
• All Communities are in the
Yakima Valley of Eastern
Washington
T nompfon ?; a! "003
the CBPR
Intervention
Sawyer
Donald
Buena
Moxee
Cowiche
Mabton
Granger
Toppenish
Labor Camps
Intervention
Bond Varner Camp
Green Giant Camp
Willow Park
Yakima Golding Farms
Project
Control
Harrah
Tieton
Outlook
Zillah
Wapato
Whilst ran
Prosser
Grandview
Control
Golding Farms Camp
Crewport
Rainbow court
Horse Heaven Mobile
Park 7
Examp
Based
le from Community
Participation Project
Thompson et al 2003
Environmental Public Health Continuum
Over 250 community-wide events occurred.
This Community Health Fair is an example.
Total number of participants at community-
wide events is greater than 6.000!
Over 1,800 total events took place in the communities.
Approx. 1,000 Home Health Parties such as this occurred.
Total number of participants in all levels
of community activities was over 18,000!
Community Intervention
Handing out toys such as
frisbees and basketballs
draws kids to the
Community Intervention
project's table where they
learn simple things to
help reduce their
exposure to pesticides.
Photo: Gloria Coronado
2
-------
Community Intervention
After a series of
presentations made in
second and third grade
classrooms, students
were invited to enter a
coloring contest. Winning
entries were included in a
calendar. In this drawing
the woman tells the man
to wash his own clothes,
because she's going to a
dance...and she reminds
him to leave his boots
outside.
Photo: Gloria Coronado
1 Handwashing Song
UtnA mf.h nri/i yaui tut**.
Cvery row jr« Mr,
Smtpy, uxky wapy. s**ky
Withiaa fund* it f»atf
Handwashing Puzzle
Sample Evaluation Question
Pablo n hungry.
He'i going to cot an appk.
What should h* do before he
(••!•• the -pf |!l" '
Which picture shwtd cwnc nest?
Agricultural Pesticides: Contributions of
Occupational Factors to Home Contamination
Metabolic Scheme for CP
(OEP)
Faustmanetat (2006) 18
-------
Metabolites of Organophosphate
Pesticides
• Biomarkers of exposure
• Nonspecific Diakyl Phosphate
(DAP) metabolites
- Six DAP Metabolites
- Each metabolite can be
produced by multiple OPs
- Divided into two groups
• Dimethyl metabolites
- DMP, DMTP, DMDTP
• Diethyl metabolites
- DEP, DETP, DEDTP
• Specific metabolites
- Chlorpyrifos metabolites
• TCP, DEP, DETP
- Chlorpyrifos-methyl metabolites
• TCP, DMP, DMTP
Metabolites of Organophosphate
Pesticides
Selected OPs and DAP metabolites
Diethyl OPs
chlorpyrifos
diazinon
disulfoton
ethion
parathion
Dimethyl OPs
azinophos methyl
chlorpyrifos methyl
dichlorvos (DDVP)
malathion
methyl parathion
naled
phosmet
trichlorfon
DEDTP
DEDTP
DMDTP
DMDTP
DMDTP
DEP
DEP
DEP
DEP
DEP
DM
DM
DM
DM
DM
DM
DM
DM
DETP
DETP
DETP
DETP
DETP
DMTP
DMTP
DMTP
DMTP
DMTP
Metab
Dlites of Organophosphate
Pesticides
Selected OPs and DAP metabolites
Diethyl OPs
chlorpyrifos DEP DETP
diazinon DEP DETP
parathion DEP DETP
disulfoton DEDTP DEP DETP
ethion DEDTP DEP DETP
Dimethyl OPs
dichlorvos (DDVP) DM
trichlorfon DM
naled DM
chlorpyrifos methyl DM DMTP
methyl parathion DM DMTP
azinophos methyl DMDTP DM DMTP
malathion DMDTP DM DMTP
phosmet DMDTP DM DMTP
21
Monitoring Results
Evidence of pesticides in environment
• 36% of homes and 42% of cars had quantifiable levels of 2 or more OPs in dust.
• 60% of households (home and vehicles together) had evidence of 2 or more OPs
in collected dust.
Monitoring Results
Most children are exposed
• 86% of children had quantifiable levels of at least one dialkyl metabolite.
• 95% of adults had quantifiable levels of at least one dialkyl metabolite.
Evidence of multiple exposures
• 36% of children had quantifiable levels of both dimethyl and diethyl metabolites.
• 45% of adults had quantifiable levels of both dimethyl and diethyl metabolites.
Evidence of Take-home Pathway
• Workers who thinned were more likely than those who did not thin to have
detectable levels of azinophos-methyl in their house dust and vehicles.
• Children of thinners were more likely to have detectable levels.
• Contrary to expectations, workers who reported mixing, loading or applying
pesticides had lower incidence of detectable pesticide residues in their homes,
vehicle dust, and in their children's urine.
•n EM, Griffith WC 2006
-------
What do these values mean for my
Children?
Samples Collected in Studies of
Farmworker Families
Types of samples collected from individuals and
their children in 3 seasons
- Urine analyzed for metabolites of OPs—collected 3
times in 1 week
- Blood analyzed for parent OPs, metabolites of OPs,
AChE in RBCs and plasma, genotypes and
phenotypes of metabolizing enzymes—collected once
- Buccal Cells analyzed for gene expression—collected
2 times in 1 week
Dust is collected from homes and autos in
thinning and non-spray seasons season and
analyzed for parent OPs
Many Values Are Below
Limits of Detection
Child DETP
Quantiles of a log normal distribution
NHANES Compared to Farmworker Family
Data for DMTP in Urine
DMP in Adult Urine: QQ Plots to
Estimate Population Distribution
Group of 8 Highi
Exposed
Individuals
Detection
Limit
Distribution of Adult DMTP from year 1:
Impact of Crop
a
l ;-
-------
Assessing Children's Pesticide Exposure
via the Take-home Pathway
Urinary metabolites higher in adults who
worked in pome fruit and their children
Adult DMTP in Urine
Child DMTP in Urine
8
Pome
Fruit
100 1000 1 10
Urinary DMTP ug/ liter
100 1000
Coronado et al., Env. Hlth. Persp., 2004, %>06
Two longitudinal studies of OP metabolites
used to estimate within and between variability
• Multiple measurements in the same person across time
permit estimation of both within and between person
variability
- Within and between person variability treated as a random effect
and other variables such as age, gender .residence, season
treated as fixed effects
• TCP had a low percentage below limits of detection
• Measurements below limit of detection (LOD) were
treated as being left censored in statistical analyses
Predictive Value Positive for Identifying Persons in
the Upper 10% of the Population
The predictive value positive is the percent of the population assigned to a group that are
correctly classified.
Is-
~
0
JS-
1
5 q"
.1
is-
1
Minnesota
. J^^* ~ "~
,s^* '" Maryland
/£•
High Rate of
Misclassification
Based upon large
within person
variances it will
require a large
number of
samples of
urinary
metabolites to
correctly identify
persons in a
population who
are more highly
exposed to CP
and CPM.
0 10 20 30 40 50 ^
Number of Measurements per Person
Sources of Uncertainty
Stochasticity
- Characterization of Within and Between Person
Variability
Parameter Uncertainty
- Year-to-Year Variability
- Observations below Limits of Detection (LOD)
Model Uncertainty
- Crop vs. Agricultural Job Task
- Identification of Highly Exposed Individuals
Biomarkers for Monitoring Exposure and
Effect in Populations
-------
Physiologic Based Toxicokinetic
Models of CP Metabolism
Environmental Public Health Continuum
Methodology Underlying
Integrated Framework Tool
Bayesian Based Mixed Effects Model
- Correlational structure of a multivariate
distribution used to estimate correlations
between pesticide concentrations,
metabolites, gene expression levels, and
other variables
- Markov chain Monte Carlo methods used for
parameter estimation
-------
1/29/2008
Social Stress, Stress Hormones and
Neurotoxins
James P. Herman, PhD
Stress Neurobiology Laboratory
Department of Psychiatry
University of Cincinnati
Stress Responses
v Anticipatory in nature:
'Caused by possible threat to homeostasis
'Generated by stimulus comparison
innate programs
learning
Reactive in nature:
'Caused by direct threat to homeostasis
'Generated by reflexive pathways
Herman and Seroogy, Neurol. Clin. 24:641 (2006)
The HPA Stress Axis and Organismic
Homeostasis: Redistribution of Resources
Short-term benefit:
*Energy mobilization
*Energy diversion
"Limits immune responses
*CNS Arousal
Lona-term conseauences:
'Metabolic Disease, obesity
'Musculoskeletal atrophy,
HPG problems
"Immune dysfunction
"Depression, PTSD(?)
-------
1/29/2008
Neurobiological Consequences of Stress
Stress-related affective disease states (depression,
PTSD) affects 10% of the population in any given
year
Stress exacerbates other affective disease states,
such as schizophrenia and bipolar disease
Stress exacerbates other organic disease
processes
Stress hormone secretion can contribute to cell
loss/cognitive decline in aging and dementia
Stress, Stress Hormones and
(Neuro)toxicity
•Stress and Neuronal Function
•Stress as a Predisposing Factor in Neurodegeneration
•Stress as a Co-morbid Condition? Implications for
Toxicology
Social Stress Shrinks Dendrites in the
Hippocampus
Control
Subordinate
Stress Reduces Neurotrophic Factor
Expression in Cortex and Hippocampus
Rats
Mice
j:
Smith et al, J. Neurosci. 15:1768 (1995)
Pizarroetal, Brain Res. 1025:10(2004)
Prenatal Stress Reduces Neurotrophic
Factor Expression in Cortex and Striatum
E
it*
HD? SIR PFCX
Fumagelli et al, Eur. J. Neurosci 20: 1384 (2004)
Social Stress Increases Abdominal Fat
Accumulation (Obesity)
Tamashiroet al., Amer. J. Physiol. 293: R1864 (2007)
-------
1/29/2008
Glucocorticoids Mediate Hippocampal Damage
Following Head Trauma
Veh Spiro Rt*4Si.
Herman and Seroogy, Neurol. Clin. 24: 461 (2006)
Stress as a Predisposing Factor in
Neurodegeneration: Other models
> Kainate neurotoxicity in hippocampus (epilepsy
model)
> Infarct size and ischemic cell death (stroke model)
> Senescence-related cognitive deficits and neuron
loss (aging and Alzheimer's Disease)
Toxins Alter Stress Axis Function
•1; -JL-I..-
White et al, Tox. App. Pharm., E-pub
Stress as a Co-morbid Condition?
Implications for Toxicology
> Stress enhances relapse of addictive behaviors
(smoking, alcohol, other drugs of abuse)
> Social stress promotes abdominal obesity
> Prenatal stress interacts with lead exposure to
alter brain neurochemistry, behavior and HPAaxis
drive
> Stress: represents one of the 'hits' in the multi-hit
hypothesis of toxicity
Stress as a Co-morbid Condition?
Implications for Risk Assessment
> Substance abuse and obesity are prevalent in
lower SES populations
> Lower SES groups have disproportionate
exposure to some environmental toxicants (e.g.,
lead)
> Environmental toxicants can modulate
glucocorticoid secretion
> Glucocorticoids enhance neurotoxic processes
Stress and Cellular Endangerment
Other
(age, disease)
-------
Stress and Cellular Endangerment
Other
(age, disease)
Stress and Cellular Endangerment
Other
(age, disease)
-------
1/29/2008
"Social Modifiers in Environmental
Neuroepidemiology: The Role of
Context in Chemical Exposure"
Robert Wright MDMPH
Department of Pediatrics,
Children's Hospital, Boston,
Department of Environmental Health
HSPH
J
Biological Vulnerability
• Construction of the central nervous system
(CMS) begins in utero,
• Continues throughout childhood and
involves the production of 100 billion nerve
cells and 1 trillion glial cells.
• Cell migrate, differentiate, and form
synapses
Synapses
Transmits signals between neurons
nEnvironmental stimuli will cause neurons to fire
nNeuronal/synaptic firing is a signaling process to
mold the synaptic architecture of the brain
How does the Brain Build this
Network?
• Some of it is stochastic
nSynapses are made by the billions, and in
some respects randomly, between neurons.
We make a net gain in synapses from fetal life
till about age 2 years
nThen the number of synapses in our brain
starts to decrease
.Why?
Synaptic Networks
Environmental Stimuli cause nerves to fire:
When they fire neurotransmitters are released
into synaptic junctions
This releases growth factors- signals that this is an
important neuronal connection (i.e. it gets used)
In other words there is a "natural selection"
process
n Functional synapses release growth factors
Nonfunctional synapses do not release the growth
factors
Hebb Synapses
TimMOthtrlnputt
»i Not Activi
-------
1/29/2008
So how do Environmental
Chemicals affect Development?
• At "low" doses (blood lead around 5-10 ug/dL)
n Lead will interact with Protein Kinase C
• Stimulate neurotransmitter release
• Neurons fire in the absence of an appropriate environmental
stimuli
n Lead mimics calcium
• Calcium is critical to nerve signal transmission
• Calcium enters neurons during depolarization
• Lead blocks calcium channels
J
Lead and the Brain
Net effect
n Lead stimulates nerves to fire in a more stochastic
fashion
n Lead also inhibits neurotransmission (both
appropriate neurotransmission and inappropriate
neurotransmission)
Changes the underlying synaptic architecture, making it
less efficient
Plasticity
The brain's capacity to diminish the effects of
toxic insults through structural/functional
changes
This occurs through the same processes as synaptic
selection
In other words plasticity allows for new connections to
be made which improve function following an insult
Maladaptive vs adaptive plasticity
Neurodevelopment and Social
Environment
1 Chronic Stress known to impair
memory and learning capacity
Example: Handling Paradigm
• Licking/grooming in mothers is stimulated
by human handling of pups.
• Maternal LG and Arch back nursing
behaviors program more appropriate long
term HPA axis response to stress.
• Maternal LG/ABN clusters in family lines
Is it genetic?
Weaver et at. Epigenetic programming by maternal behavior
Nature Neuroscience \ Volume 7\ Number 8\August 2004
low LG and ABN
mothers
high LG and ABN
mothers
P-
Fearful offspring with brisk HPA stress
Less fearful offspring with more modest HPA stress
response
-------
1/29/2008
EFFECTS OF CROSS-FOSTERING
low \J& and ABN mothers high \J& and ABN mothers
Fearful offspring with brisk HPA s
•esponse Les!. fetrfu| offspring with more modest HPA stress
J
Programming And Epigenetics
• Fetal origins of Disease
Prenatal (and early life exposures), increase
risk of late life disease
. HTN,
• Obesity
nHandling paradigm is an example of neuro-
programming
•Methylation of histone or of DMA usually turns a gene off.
•Acetylation of histone usually turns a gene on.
•Phosphorylation - we're not sure what that does.
The Histone Code
Epigenetics and the Brain
Epigenetics plays an important role in
synaptic pruning via environmental stimuli.
• Epigenetic marks within neurons change with
synaptic activity
This "epigenetic opening" of synaptogenesis
to environment is maximal during childhood
nit is the source of the exceptional cognitive
adaptability of humans, and possibly the
source of its fragility
Handling Paradigm
Weaver et al
Glucocorticoid receptor expression is more active
in offspring of high-US mothers compared with
low- \J& mothers,
Effect inversely correlated with methylation
across Glucocortoid Receptor promoter sequence
in the hippocampus
REGARDLESS OF GENETIC BACKGROUND
Social Environment and Pb
• Guilarte et al
• Lead poisoned animals during lactation
• Randomized to 2 groups
nAnimals raised in social isolation
Animals raised in groups with social
stimulation
• Tested on memory in Water maze
-------
1/29/2008
5.100
I».
5 «
Acquisition Time
ml
Probe Test
E-Hiiu I-HHI E-fb i-Pb
Condition
E-H20 I-H20 I I'h l-Pb
Condition
Can Reducing Stress be a
Treatment?
• Mexico City
• Coopersmith self-esteem administered to
mothers when child 24 months of age
• Cross-sectional analysis
• Covariates
Blood Pb, mom's IQ, mom's education, child's
sex,
Main Effect of Maternal
Self-Esteem
Blood Pb
autoes |
-.11 0.569
.46 0.006
. 78
Blood Pb and MDI
Self esteem
Quartile 1,2,3
Self esteem
Quartile 4
i '••"
Another Pilot Study: Maternal Child
Lung Study
• Pregnancy cohort recruited from 1986-1992
• Study of in utero/environmental tobacco smoke
exposure and respiratory outcomes
• Women enrolled before 20th EGA week
• Children followed after birth
• Measured ETV (violence) and WCST as pilot
-------
1/29/2008
Effect of Cotinine in Predicting Errors on WCST:
Stratified by Median Violence Exposure
% Errors
# Perseverative
Responses
%Perseverative
Responses
# Perseverative
Errors
% Perseverative
Errors
Cotinine Beta (Low
violence)
2.9 (p=0.6)
1.7(p=0.7)
2.0(p=0.7)
0.8 (p=0.9)
1.4(p=0.8)
Cotinine Beta (High
violence)
9.8 (p=0.07)
11.1 (p=0.007)
10.7(p=0.007)
10.7(p=0.01)
9.9 (p=0.02)
Mexico Birth cohort
• The work just reviewed led to the
establishment of a new birth cohort in
Mexico City.
• R01 ES013744 Stress, Lead, Iron
Deficiency and Neurodevelopment.
•posurc in Mexico to
Cdl Toxicants Project
Mexico City Cohort
• Long term goals
Identify factors that increase/decrease metal
toxicity
Understand the biology of metal neurotoxicity
Prevent toxicity
nTreat toxicity after it has occurred
Tar Creek Superfund Site
-------
1/29/2008
The MATCH Study
(Metals Assessment Targeting Community
Health)
"Ga-Du-Gi"- Working Together
Thanks
Element
Adrienne Ettinger
Mara Tellez-Rojo
Hector Lamadrid
David Bellinger
Rosalind Wright
Howard Hu
Lourdes Schnaas
Adriana Mercado
Tar Creek
David Bellinger
Adrienne Ettinger
Rosalind Wright
Howard Hu
Mary Happy
Mark Osborn
Rebecca Jim
Earl Hatley
-------
Outline
rjUse some examples to
- Illustrate challenges
- Describe useful statistical tools and areas
where more research would be helpful
QMy examples
- Classic cancer cluster investigation
- Home Allergen Study
- Exposure assessment for various Boston
based studies
- Mercury and IQ
Cancer risks
on Cape Cod
LJCitizens near air-force base concerned about
excess cancer rates reported on upper cape
iCIear evidence of multiple exposures
U Excesses small to moderate (SIRs around 120)
Power limited by total pop of ~30K
- No individual exposure assessment
Cape Cod - continued
_lData very noisy - smoothing no help
QVery frustrating experience for all
JNeed guidelines on what's achievable
Home Allergen Study
1 Mother/child pairs recruited at birth. Followed for
asthma, allergy, respiratory disease
1 Interest in allergens, molds, adjusting for social factors
Geocode study subjects and assign areal level
characteristics (e.g. based on census)
Intriging geographical variation
in maternal serum IGE. But
geoadditive modeling (Kammen
& Wand) suggests "hotspot"
confounded with race, poverty.
Boston and New England studies of
cardiovascular response to air pollution
J Estimate exposure from
- EPA EC monitors
- Various Indoor & outdoor
monitors (different studies)
- CIS-based measures (traffic
density, potentially climate,
land use etc)
J Goal - relate predicted
exposures to health outcomes
(heart rate variability,
arythmias, birth weight),
accounting for estimation error
J Latent variable formulation very
promising
h(lat, Ion) + e
-------
Note
Q Higher predictions
near main roads
Q Smoothness of
estimated surface
elsewhere
Further directions
Q Use "science-based"
models to inform the
modeling (Fuentes
and Raftery, 2005).
Q Unusual data sources
(e.g. satellites)
Features so far
Sparse data
Clever combination of data from multiple
sources
Spatio-temporal modeling
Lets look at another example (methyl mercury)
where hierarchical model helps to make sense
of limited data. Not a classic community-
based risk assessment, but illustrates many
of the ideas
Mercury
OReleased by coal-burning powerplants,
bioaccumulates through foodchain to
methylmercury, human exposure via
fish consumption
QHigh level exposures
clearly toxic, low level
chronic effects
controversial
h Convumptlon Impact* Our Mwoiry E
The controversy
Q Conflicting conclusions from two large, well
conducted epidemiological studies
Seychelles study (n=779) - no effect
Faroes study (n=1022) - effects
Both studies
- had prenatal enrollment
had reliable biomarkers of exposure
- adjusted for similar important confounders
- measured similar outcomes
QNAS confirmed quality of both studies, identifed a
third. Argued against focus on p-values. Studies less
discrepant if focus is on dose response estimation.
MEHG and IQ (7-9 years)
QIQ has been
"monetized"
QIQ is related to other
end points
QStudy results
-.50 (.28) (NZ)
-.17 (.13) (Seychelles)
-.13 (.061) (Faroes)
QCan we combine data?
Estimated regression
coefficients and 95% CIs
-------
Q-IQ
-
B - Boston Naming
C - California
Verbal Learning
X - other cognitive
endpoints
Dashed line - no
effect
Hierarchical Modeling Results
Q Not enough data to reliably estimate separate study and
endpoint variance components
Q Assume a2study = Ra2endpoint and repeat for different R
[{
3.0
2.5
2
1.5
1.0
.5
.4
.25
"„,„
.0343
.0379
.0429
.0499
.0612
.0420
.0371
.0286
*(»e)
(.0303)
(.0328)
(.0362)
(.0408)
(.0476)
(.0505)
(.0324)
(.0262)
IH
-.125
-.120
-0.128
(se)
(.054)
(.0559)
(0.0587)
-0.131 (.063)
-0.136 (.0699)
-0.127
-0.126
-0.123
(0.0569)
(.or, in
(.0498)
II.Y; c,
(-0.248.
(-0.256.
(-0.265.
(-0.281,
(-0.305.
inf. lui
-0.034)
-0.033)
-0.030)
-0.028)
-0.023)
(-0.259.-0.031)
(-0.251, -0.033)
(-0.236, -0.037)
Die*
-3.704
-3.873
-4.112
-4.
-4.
-1.
-3
-3
455
097
103
846
423
* Smaller values of DIG indicate better fit 15
More sensitivity analyses
QHair/blood ratio
[^Alternative scaling of Faroes IQ -
estimated IQ effect strengthens to -.23
AllillvM-
Hiiit..-|iU>il niliii' g.r.j. IM-I
•IV, I'niil Ini
Ex. In. I.' XZ. mlli. •!
r.x, In.ii. NX,™ II. T
In. In.!.' NX ..iirt.-i
In. lii.l" NX ..... HIT
Altrriliilivr K..1.H- h
-j-.il
•xa
250
200
-.'•HP
All. -I
.il if I '!•". I' i
.IIMI (JUT-I) -.115 (.IIKr)) (-Ir'liG.-IMIIS)
-o.iiii (.1x1:121 (-i).jsi. -o.o-js]
-0.090 (.0360) (-O.irj. .11.025)
IUMI'I (.!>»>.>) .0.utf (JPrei I.U.SIH. .ii.irr.1
am;?I.IHBII .11.MI.: IHPII (.iur,i. .ip.iaii
-------
What have we learned?
Uncertainty tends to be large when dealing with data
collected in real world communities
Need to measure characteristics of community, as well
as individuals
Major benefits to statistical techniques (Bayes) to
sythesize information from multiple sources
• Data (similar or unrelated studies)
• Expert opinion
Some good tools around Bayes was a
• Spatio-temporal models bad boy" Pasky
• Hierarchical models
Don't over-interpret model results, p-values.
Do lots of sensitivity analysis
Remaining frontiers?
Spatio-temporal models still relatively primitive
Good tools around for combining information.
Further work needed to finesse them to handle
multiple scales, levels of accuracy etc
S Design a neglected topic! We've worked with
Battelle to develop strategies for clever
subsampling to maximize information/minimize
cost. Working on extensions to spatial setting
(with ACC funding)
Multi-Stage Sampling Paradigm
Population of interest
Stage I sample — Y (outcome) and
Z (cheap easy) measured
Stage II — more expensive
accurate measures
Stage III - different
expensive, accurate
Case Example
Y ~ Bin(PY = 0.003) Cost associated with measuring Y = $20
X ~ N(0,1) Cost for exposure assessment = $1000
YX = 2.0 Odds ratio between X and Y
I Total Cohort Size = 100,000
Surrogate Z costs $50 and has correlation .5 with X
We determined designs with 80% power
Random Sample
Cost j N
Covariate Dependent
Sample (for X)
Cost I N
Outcome Dependent Sample
(forX)
Cost
N
Analyze
subset only
Incorporate
surrogate
Cost = $5.606.940 n =5,497
nz=23,319
ny=23,686
nz=23,686
4
-------
Adjusting for drinking variation
Consider outcome for a single individual and suppose
Logit(Pr(Y=1)=p0+p1*D*C
D = amount drunk, C = concentration in the water
D is unobserved, but
distribution estimable from an
EPA survey.
What is impact on estimation
of p., (compared to assigning
everyone their village well
concentration)?
Impact on Benchmark Dose
(dose corresponding to 1% risk)
Adjustment?
No
Yes
BMD BMDL
165 145
195 :
Thanks!
Come to Duke tomorrow for more details
on the sub-sampling project
mean of posterior distribution
lower 5% percentile
-------
A Multi-Site Time Series Study of
Hospital Admissions and Fine
Particles:
A Case-Study for National Public
Health Surveillance
Francesca Dominici
ffdominic@ihsph.edu)
Department of Biostatistics
Johns Hopkins Bloomberg School of Public Health
EPA Workshop October 17 2OO7
Sponsored by the EPA, CDC Center of Excellence, and NIEHS
A NATIONAL SYSTEM FOR TRACKING
POPULATION HEALTH
Multiple government databases contain
massive amounts of information on the
environmental, social, and economic factors
that determine health
Research on population health could be
rapidly advanced by:
- integrating these existing databases
- bringing to bear new statistical models that
would describe major threats and their causes
These integrated databases and new
analysis tools would create a national
system for population health research
Air pollution and health:
Fundamental questions
• Is there a risk at current levels?
• How can we estimate it?
• How big is the risk?
• What causes it?
Health Effects Fine Particles:
Objectives
1. assemble a national database of time series
data for the period 1999-2005 on hospital
admissions rates for cardiovascular and
respiratory diseases, fine particulates, and
weather for 204 US counties
2. develop state-of-the-art statistical methods
3. estimate maps of relative risks of hospital
admissions associated with short-term
changes in fine particles
4. illustrate how integration and analysis of
national databases can lead to a national
health monitoring system
Integrating National Data Sources
NCHF: 48 million identification numbers
MCBS: subset of 15,000 Medicare
participants with additional information
on risk factors
AIRS: air pollution monitoring network
NOAA: weather monitoring network
US Census: location characteristics
Integrating national data bases
Health Pollution
-.' ' -• ' v-' »: Jc <-» ' i
L3uS» _ VT S/^V^
-------
U.S. population / Medicare beneficiaries
Age 65 +
2000
Medicare beneficiarii
Age
National Medicare Cohort
(1999-2005)
National study of fine particles (PM2.5)
and hospital admissions in Medicare'
Data include:
- Billing claims (NCHF) for everyone over
65 enrolled in Medicare (~48 million
people),
• date of service
• treatment, disease (ICD 9), costs
• age, gender, and race
• place of residence (ZIP code/county)
- Approximately 204 counties linked to the
air pollution monitoring
MCAPS study population: 204 counties with populations larger
than 200,000 (11.5 million people)
! i I 1 I i
Population (mlllam)
Daily time series of hospitalization rates and PM2 5
levels in Los Angeles county (1999-2005)
2000 2002 2004 2006
COPD
2000 2O02 2004 2006
2QCQ 2002 2004 2QC5
2002 2004 20C5
Multi-site time series studies
• Compare day-to-day variations in
hospital admission rates with day-to-
day variations in pollution levels
within the same community
• Avoid problem of unmeasured
differences among populations
• Key confounders
^Seasonal effects of infectious
diseases and weather
Statistical Methods
• Within city. Semi-parametric regressions for
estimating associations between day-to-day
variations in air pollution and mortality
controlling for confounding factors
• Across cities. Hierarchical Models for
estimating:
- national-average relative rate
- Regional-average relative rate
- exploring heterogeneity of air pollution effects
across the country
-------
Challenges
• For any given city, we try to estimate a
small pollution effect relative to
confounding effects of trend, season and
weather
• Strong role of other time-dependent factors
• High correlation between non linear
predictors
• Sensitivity of findings to model
specifications
JAMA'
cil!Ic;INAI,c:clNTOII)IITIMN
Fine Participate Air Pollution and
Hospital Admission for Cardiovascular
and Respiratory Diseases
Roper D. EVnjv. Itil*
Jonathan M. Sanm, Ml)
March 8 2005
particle! (particular rrutli?i --2 5 |im in .ino'ikii.iit i. Ji.iin^tr-r [PiV.;;]) is limited. Re-
research on health risks at national and regional scales.
Objectives To estimate risks of cardiovascular and respiratory hospital admissions
associated with short-term exposure to PMif for Medicare enrollees and to explore
Design, Setting, and Participant* A national database cornpnsing daily time-
Figure 2. Percentage Change in Hospital izaton Rate by C
PMJ5 on Average Across 204 US Counties
Injury
LogD • —
Lag! •
Lag? •
Osfebrc'.'»: JIT Crmsse
Lag »
Lag •-
F^ripfe Vascular Detain
tag »
Lag
Lag
Lag
Lag i
Heart R ^Im
Lag
S,
H^rt Fa ui&
Lag
Lag
Lag
Lag
Lag
Tola!
tig —
Lag !
% Change In tospflal Admlsaon
useperlO-pg/mMncreasein
Injury admissions
"sham"
_-— —
— • —
• Cardiovascular
* admissions
— • —
• , Respiratory
_. admissions
New Scientific Questions
What are the mechanisms of
PM toxicity?
> Size?
> Chemical components?
> Sources?
Emission Chemical
sources constituents
Size Total mass
Air pollution and health:
Questions and (some) answers
• Is there a risk?
> Multi-site time series studies such as NMMAPS
(1987—2000) provide strong evidence of short-
term association between air pollution and
mortality
> Preliminary results from Medicare data (1999—
2002) indicate that current air pollution levels still
affect health
• How can we estimate it?
> National datasets are powerful resources for
assessing the health effects of air pollution
> Statistical models that can integrate information
across space and time
> National average estimates for the effect of PM
are robust to various model formulations and
statistical methods
-------
Reproducible research
We want to reproduce previous findings
- "Did you do what you said you did?"
Test assumptions, robustness of findings;
check methodology
- "Is what you did any good?"
Implement and test new methodology
- "I can do it better!"
Discussion
Linking national databases and developing
statistical methods that can properly
analyze these them, are essential steps for a
successful national public health tracking
system
Because of the small risks to be detected
and the large number of potential
confounders, single-site studies are
generally swamped by statistical error
A national system, that routinely analyze
data from multiple locations in a systematic
fashion, is a very promising approach for
tracking population health
Explosion of Information
e.g.
large databases
on population health and exposure
to potentially toxic agents
Expertise in:
• Integration of complex
databases
•Statistical Methods
• Reproducibility
More confusion
More knowledge and
Better health risk assessment
Acknowledgments
Our team:
- R. Peng
- S.Zeger
- J. Samet
- A. McDermott
- M. Bell
- L. Pham
Our sponsors:
- EPA
- JHU CDC Center
of Excellence
- NIEHS
-------
Risk Assessment/Risk
Communication-Understanding
the Community
Thomas Schlenker, MD, MPH
Public Health Madison-Dane County
Lead Human Exposure and Health Risk
Volume 1, July 2007
c?
i
Sources
Pathways
Routes
Populations
Internal Disposition
Endpoints
Risk Metrics
Community-based Risk
Assessment: Lead
Benjamin Franklin
Voluminous Research
National Strategies
Substantial Funding
PIONEER
Bone, Blood, CNS
Internal Disposition
— Harmless/harmful
- Hgb, RBCs and breast
feeding
- Developing brain and
synapse story
Chips vs Dust
Sources
Pathways
- Pica
— Child growth/dev
- Housing
- Weather
— Abatement
— Dust wipes
-------
Mothers, babies, doctors and
public health
Routes
Populations
— "community-based research
framework and a
transparent process to instill
confidence and trust among
community members"
- "Effects of Lead in
Milwaukee's Water." Wis
MedJ 1989:88:13
IQ and high school graduation
Risk Metrics
- Herb Needleman in
Somerville, Mass
Community-based Risk
Assessment: Manganese
Sources
Pathways
Routes
Populations
Internal
Disposition
Endpoints
Risk Metrics
EPA Resources
Health Effects Support Document for Manganese,
2003: HRL = 0.30 mg/L
Drinking Water Health Advisory for Manganese, 2004:
lifetime health advisory value
Teach (Toxicity and Exposure Assessment for
Children's Health) Manganese Chemical Summary,
2007: infant formula
Occurrence of Manganese in Drinking Water and
Manganese Control (EPA/Awwa Research Foundation):
"aesthetic problem...relates more to consumer complaints
rather than protecting health."
Sludge vs Sediment
Pathways
- Wells
— Mains
- Laterals
— Hose bibs
-------
Food, Drink, Osteo-Bi-Flex
Sources
— Concentrations
- Bioavailability
- Volume
— Consumer Products
At Risk vs Worried Well
Populations
— "Population factors that
differentially affect
c-Ap'.^ire or loxicity, and
in some cases, resiliency
to environmental
contaminants."
- Infant formula: "contains
50 to 300 ug/L of
manganese" (Collipp et
al,1983)
Human Impact
Endpoints
Risk Metrics
- Parkinson's Syndrome
- ADHD
- Hair analysis?
It must be the water!
Risk Communication
-------
Perspectives, issues and needs in
community-based risk assessment
USEPA Workshop on Research Needs for
Community-Based Risk Assessment
October 19, 2007, Research Triangle Park NC
George Bollweg PhD
USEPA Region 5 Air and Radiation Division
bollweg .georaeOepa .gov
312-353-5598
1
Outline for this talk
One definition of community-based risk
assessment (CBRA)
Some CBRA conceptual approaches
Influence of participant perspective on needs
Issues and needs encountered in risk
assessments with community participants
(organized per 2003 USEPA Framework for
Cumulative Risk Assessment)
USEPA tools and approaches for CBRA
Summary
i
One definition of community-
based risk assessment
According to the Workshop website,
"Community-based risk assessment is a model that
addresses the multiple chemical and non-chemical
stressors faced by a community, while incorporating
a community-based participatory research framework
and a transparent process to instill confidence and
trust among community members."
(http://www.scgcorp.com/riskassessments/index.htm)
M
1996 NRC "Understanding Risk" p. 28
(http://books.nap.edu/openbook.php?isbn=030905396X)
1997 Presidential/Congressional Commission on
Risk Assessment and Risk Management vol. 1
(http://www.riskworld.com/ Nreports/ 1997/riskrpt/pdf/ EPAJAN.PDF]
2003 USEPA Framework for Cumulative
Risk Assessment, p. 13
(http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944)
Planning, Scoping, and
I'luhkin roun illation
Analysis
i r
lull I1]) relation ami
Risk Characterization
-------
Analytic focus/orientation -
agent/stressor, community/host
(2003 Framework for Cumulative Risk Assessment, p. 1-2)
i-i. Cbcnlal (or fl
. limits. Jim iK- civm
I rufcv kjLUil :t^L-vMiw'ni\ mu'f C-K
|>ursin- smi>L' or .ill patlm.ij v ni
Hyatt 1-2. A>pu[fliL>n-hJutf *Afi
vUH wiihihe rea'p4orv and (i-ic-mi
whal chcmiL-aKlrrsMiiv iw .ilk* r
IdtA'irs JTC jtlk't Jiii. llitm.
CBRA-oriented toxicity assessment might
put prior slide in the following words:
"...Our guiding thesis is that toxicity is not simply
an inherent property of the toxicant but derives
from an assortment of jointly acting variables
bound implacably into the individual."
Weiss B, Bellinger DC. Social ecology of children's vulnerability to
environmental pollutants. 2006 EHP 114, 10: 1479-1485
Needs: influence of a hypothetical
CBRA participant's perspective
Community members - need timely "answers"
Research scientists - need timely publications
Industry participants - need to persuade affected
parties that risks are "acceptable"
USEPA managers - need to address management
priorities (e.g. GPRA goals)
State, Regional risk assessors - need to conduct
credible assessments that address participant needs
General CBRA needs - examples
Resources: community assessment can require big,
multi-disciplinary commitment and follow-through
(expertise, people, organization, time, etc.)
Host- and media-integrated human health risk
assessment methods that unify stressor- and host-focus
as well as USEPA Programs fragmented by environmental
medium or law (relevant parts of Superfund, RCRA,
Pesticides, Air, Water, RAF etc. methods?)
Air Program: combined metric for criteria pollutant and
noncriteria pollutant hazards or risks: is "composite risk
characterization" (separate presentation) enough?
Should metrics be combined?
Yes: if needed, feasible and if "combining" is logically
consistent and interpretable
No: if "combining" results in excessive information loss,
hidden incompatibilities, subjectivity, interpretability/
communication problems, false precision, etc.
(Figure from &eg Paoli; http://www.iom.edu/7id =32160)
General CBRA needs - examples
Exclusion of "background" stressor exposure or
susceptibility —> incremental assessments irrelevant
to some participants. Possible remedies:
(a) address site-specific "background" susceptibility
and/or stressor exposures; or
(b) lacking site-specific information, derive a
"reference human exposure profile" to [median??]
environmental pollutants to which incremental
exposures could be added (e.g. use Exposure Factors
Handbook and Pesticides Program info??)
-------
CBRA planning, scoping and problem
formulation: example issues, needs
Methods for choosing participants from "the
community"? (in addition to technical experts and self-
selectees)
Scoping: facilitated meeting among...(?) to formulate
analytic problem(s) and scope
Getting right science (e.g. info on substandard
housing, neighborhood crime) as well as getting
science right (i.e. pollutant exposure concentrations)
How to include "background" stressor exposures,
pollutant and/or nonchemical
Update July 1997 planning and scoping "Guidance"
(http://www.epa.aov/OSA/spc/pdfs/cumrisk2.pdfl?
,ai
k
2002 USEPA "Lessons Learned on Planning
md Scoping": some orienting questions
('http://www.epa.aov/05A/spc/pdf5/handbook.pdf, p. D-7)
1. Who are the parties proposing the assessment?
2. Are there other interested or affected parties?
3. What questions do the parties want the assessment
to answer?
4. What analysis will be done to answer these questions?
5. Who will conduct the analysis?
6. When are the assessment results needed?
7. Who will pay for the assessment?
8. How will the assessment results be used?
CBRA analysis: example issues, needs
More timely IRIS assessments/reassessments (also
needed: evaluation of organizational and political
influences [levels of review; executive branch process
control] on IRIS productivity?)
MOA determinations e.g. for benzene
Short term RfCs e.g. benzene, naphthalene
Limits of Haber's Rule
Assertion that local residents' health is "poorer
than national averages" and not addressed in USEPA
exposure and toxicity estimates - how to evaluate this in
CBRA context? If true, how to address?
1
CBRA analysis: example issues, needs
Are ~20-yr old meteorology datasets appropriate
for simulating local weather patterns 30-70 years
in the future?
Appropriateness of data from fixed-site air
monitors as surrogate for human exposure
concentrations (e.g DEARS Detroit study)
Synergistic or antagonistic toxic effects - how
likely in some mixtures?
Feasibility of an all-species (including humans)
hazard quotient or hazard index
CBRA risk characterization and
interpretation: example issues, needs
Better communicate hypothetical vs. actuarial numeric
risks (e.g. provide lifestyle-risk context?); accurate and
balanced characterization (i.e. not just "the number")
Characterizing and communicating "cascading"
uncertainty, e.g. formal vs. descriptive methods
What are attributes of successful/unsuccessful
deliberative processes (e.g. CARE experiences)?
Should a formal evaluation step (per 1996 NRC, 1997
PCCRARM) be included in USEPA risk assessments?
Expectations management? i.e. USEPA role in addressing
socially-embedded issues
Examples of CBRA approaches, guidance
and tools available through USEPA
Community Action for a Renewed Environment, CARE
(http://www.epa.gov/care). Competitive grant program to help communities
organize and take action to reduce toxic pollution in local environment
Community Air Screening How-To Manual
f http://www.epa.gov/oppt/cahp/pubs/howto.htrrO
ATRA vol. 3-Community-Scale Assessment
(http://www.epa.gov/ttn/fera/risk atra vol3.html), especially Chapters 10-12,
a sort of "CARE how-to" guide
RAGS Part A supplement-Community Involvement in
Superfund Risk Assessments
(http://www.epa.gov/oswer/riskassessment/ragsa/pdf/ci ra.pdfi
RCRA Public Participation Manual
f http://www.epa.gov/epaoswer/hazwaste/permit/pubpart/manual.htrrO
OSA/SPC/RAF Cumulative Risk Assessment Program
http://www.epa.gov/05A/spc/2cumrisk.htm
-------
4
Summary
CBRA attempts to address real-world human
susceptibility, exposure and risk with inclusive, often
resource-intensive deliberative process
Some CBRA conceptual approaches and tools are
already available
CBRA needs to:
• process multiple, diverse participant input to better identify
and formulate problems;
• help unify fragmented disciplinary "silos";
• acquire needed science to address questions/issues of
participant concern (long term commitment)
-------
October 19, 2007
US EPA Workshop on Research
Needs for Community Based
Risk Assessment
A Brief Cumulative Risk History
Closing Remarks
Michael A. Callahan
U. S. EPA Region 6
Dallas, Texas
1970s - knowledge without ability
1983-NRC Red Book
1980s - Environmental Justice questions
1996 - Food Quality Protection Act
1996 - Browner Memo on Cumulative Risk
1999 - Risk Assessment Forum Tech Panel
on Cumulative Risk Assessment formed
2000s - Pesticides assessments, NATA,
DBPs, etc.
2003 - Framework for Cumulative Risk
Assessment
2007 - RAF Case Studies Report
Cumulative Risk Technical Panel Phase 2
Why Should We Invest in Community Based
Cumulative Risk Assessment?
Issue Papers (EHP mini-monograph Frontiers in
Cumulative Risk Assessment, Vol. 115 No. 5, May, 2007)
- If Cumulative Risk Assessment Is the Answe
(Callahan & Sexton)
- A Phased Approach for Assessing Combined
Stressors (Menzie et al)
- Vulnerability as a Function of Individual and
Cumulative Risk Assessment (deFur, et al)
roup Resources in
Assessing Cumulative Health Risks from Exposure to Environmental
Mixtures- Three Fundamental Questions (Sexton & Hattis)
Using Biomarkersto Inform Cumulative Risk Assessment (Ryan, et z
Issues, Case Studies, and Research Needs in
Cumulative Risk Assessment (late 2007)
Communities are asking for it
EPA's relevance with the public is at stake
Fairness
What kind of investment?
Page 1
-------
Some Losses Potentially Not Covered.
Unreconciled Loss: Physical and Symbolic
Loss of extended
family relationships
Loss of rights
Loss of connection to
land
Loss of sovereignty
Loss of cultural pride
Loss of language Loss of spirituality
Loss of sense of Loss of autonomy
belonging
Loss of self-sufficiency Loss of social structure
Loss of culture and
tradition
Loss of history
Loss of community
Loss of identity
Loss of control
Loss of life: Multiple traumatic deaths related to disease, violence,
genetic risk factors...
ource: Lemay and Piotrowski, 2002
Relevance/Credibility
EPA Priorities:
- Legislated mandates
- Court orders
- Political issues/Media circuses
Public needs:
- Federal government as a monolith
» Can't help with problem
» Paternalism = change the problem
» Understand and help
Risk assessments that consider part of
the problem
Page 2
-------
Fairness: Vulnerability
Vulnerability: The state of being open to harm
due to the inability to cope with a hazard
because of biological susceptibility, prior
exposure or disease state, or lack of the
resources for resilience.
Vulnerability = Hazard + Inability to cope
Vulnerability can mean that the exact same
exposure can result in widely different effects
Levels of Coping
First Stage: Non-erosive Coping, includes insurance,
risk-minimizing, loss management, loans, reduction
in dietary intake, cheaper foods, reduction of meals,
sale of small stock and non-productive assets
Second Stage: Erosive Coping, includes disposal of
productive assets, shark loans, sale of large
livestock, land and tools, bonded labor
arrangements, child labor
Third Stage: Failed Coping, results in destitution,
dependency on charity, out-migration, and in
extreme cases prostitution, or even sale of children.
(WHO, 1998)
So Why Invest?
Demand starting now and will increase
Invest in Agency's relevance/credibility
Fairness
Not mission creep
Can start to buy in at modest levels
PageS
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
U.S. EPA Workshop on Research Needs for
Community-Based Risk Assessment
U.S. Environmental Protection Agency
Main Campus, Building C
Research Triangle Park, NC
October 18-19, 2007
SUMMARY
INTRODUCTION AND OVERVIEW
The U.S. Environmental Protection Agency (EPA) Workshop on Research Needs for Community-Based
Risk Assessments was held on October 18-19, 2007, in Research Triangle Park (RTP), North Carolina.
The workshop brought together researchers from academia, private industry, regulatory agencies, and
government to discuss ongoing and potential research on community-based risk assessments. The
workshop also served as a stimulus for increased collaborations among the various researchers and
agencies and resulted in improved knowledge of toxins in the environment. Approximately 85 individuals
attended the workshop.
Ms. Deborah Segal, EPA, opened the meeting. She welcomed the participants, explained the logistics of
the RTP meeting site, and introduced Dr. Hugh Tilson, EPA, National Program Director for Health.
DAY 1: OCTOBER 18, 2007
Welcoming Remarks
Hugh Tilson, U.S. EPA
Dr. Tilson welcomed participants to the meeting and to the RTP facility, which is one of EPA's greener
facilities. He explained that there are many Office of Research and Development programs that involve
human health, but the Human Health Research Program (HHRP) is the only crosscutting program that
addresses multimedia and regional issues. The main objective of the HHRP is to reduce uncertainties
associated with the risk assessment process by providing a greater understanding of exposures to environ-
mental stressors and the basic biological changes that follow. The four Long-Term Goals (LTGs) of the
program address crosscutting issues that most EPA offices and regions must manage. LTG 2, regarding
characterization of aggregate and cumulative risk assessment, is the LTG most applicable to this
workshop. EPA is increasingly being called to provide risk assessments for "super chemicals" and to
determine how these interact with nonchemical stressors. There are several scientific questions driving
research on cumulative risk, including those regarding available biomarkers, exposure models, and
information about mode of action and exposure that can improve risk assessments. The question of how
cumulative risk can be assessed at the community level has emerged in the previous 2-3 years. This
workshop is important for participants to help EPA identify and address priority issues in this area. The
program's goals regarding this issue are to: (1) develop tools and a framework to assess interaction of
environmental chemical and nonchemical stressors at the community level, (2) support research on
assessing exposure and health risk of tribes as a result of cultural practices, and (3) evaluate tools for use
in assessing community risk.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Keynote Address: A Perspective on Community-Based Risk Assessments
Linda Sheldon, U.S. EPA
The fundamental concepts regarding community-based risk assessments (CBRA) are that: (1) not all
communities are the same, (2) different communities can have differential risks as a result of exposure to
environmental contaminants and other stressors, (3) the same community can have differential risks over
time, (4) many of EPA's regulations do not consider these differences, and (5) many communities may be
at higher risk because they are not adequately protected through environmental regulations and/or
distribution of social benefits. Obvious environmental problems prompted the formation of EPA, and the
Agency has addressed many environmental concerns successfully, but some communities still remain at
risk. The Food Quality Protection Act defines cumulative risk as involving exposure to two or more
pesticides, but it is important to consider nonchemical stressor impacts as well. For the purpose of this
workshop, cumulative risk can be defined as the combined risks from aggregate exposures to multiple
agents or stressors. Cumulative risk assessment is an analysis, characterization, and possible
quantification of the combined risks to health or the environment from multiple agents or stressors.
Risk assessors must consider the following questions: (1) How do we identify the most important risks in
these communities? (2) How do we assess the cumulative risk in these communities? (3) How do we
develop appropriate risk mitigation procedures? (4) How do we demonstrate that we made a positive
impact? During the past 3-4 years, the National Exposure Research Laboratory (NERL) expanded its
aggregate risk research to include cumulative risk. In doing so, researchers then needed to consider
multiple stressors and community conditions. Ecologists always consider communities (i.e., ecosystems)
and the entire range of stressors and the condition of the ecosystem as a result of cascading effects.
Ecologists have developed models and GIS tools that should be applicable to human health risk
assessment; ecologists are valuable resources and potential partners for risk assessors.
During the recent International Society of Exposure Analysis (ISEA) 17th Annual Conference, a number
of scientists, including Drs. Marie Lynn Miranda and Marc Serre, presented data on the application of
advanced statistical, GIS, and modeling tools to understand exposure and risk. Dr. Miranda is applying
spatial tools to CBRA research, and Dr. Serre is examining the spatial and temporal distributions of
stressors in the community that allow estimates of pollutants in the community over space and time.
Science, tools, communication, partnerships, and trust are needed to advance CBRA research. To build
the science, the source-to-health outcome continuum (environmental release, environmental concen-
trations, exposures concentrations, target organ dose, early biological effects, adverse outcomes) should
guide the core research that is conducted to determine exposure and health risks. An emphasis should be
placed on building the tools, including simple and low-cost monitoring methods, GIS tools, models for
exposure, comparative databases, tools for interpretation, and primers for conducting assessments and
using the tools. These tools must be developed for and used by the community. To build communication
with the community, scientists must "keep it simple." Researchers must listen to the community, hear its
concerns, and know how the community is different and how this difference impacts community risk.
Researchers should describe the science in simple terms, including the issues, what is known, and what
can be changed. All researchers must be involved with the community at some level.
A paradigm shift for the Agency is the transformation from decision-making to providing technical assis-
tance to help communities make decisions. Exposure and risk analysis has shifted from analysis done for
the community to partnering in a deliberative process. Communities want to know what the possible
exposures are and have concerns regarding exposures addressed; this often is more subjective than objec-
tive. CBRA is important because researchers have an opportunity to make a difference. It is hard work
because CBRA is multidisciplinary, communities must be involved, and impact is an important issue.
Technology exists that makes CBRA research possible, and it is improving steadily. This workshop is
focused on bringing all of these factors together to improve CBRA research.
The Office of Research and Development's National Center for Environmental Research 2
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Summary of Session—"Exposure Assessment Methods in Community-Based Risk Assessment" From
the International Society of Exposure Analysis (ISEA) 17th Annual Conference
Brad Schultz, U.S. EPA
Mr. Schultz summarized the session that he co-chaired with Dr. Valerie Zartarian at the recent ISEA
Conference. The session started with a brief overview of the Community Action for a Renewed
Environment (CARE) Program, which coordinates EPA program and regional offices and the Centers for
Disease Control and Prevention (CDC) via a memorandum of understanding; the program also supple-
ments EPA regulations to support community-driven risk assessment and risk management. One level of
CARE research includes risk prioritization and the selection of risk reduction activities, whereas a second
level involves risk reduction and quantification of effects. The session also included a CARE technical
issues overview by the environmental health assessment co-chair, EPA Regions 1 and 6 case studies, the
status of EPA cumulative assessment guidance, and an overview of EPA work on the National Children's
Study (NCS). A NERL principal investigator provided a summary of exposure tools research;
collaborations with health scientists, risk assessors, and the CARE Program; NCS exposure assessment
research; and research involving measurement methods and modeling. One attractive idea that was
discussed was the use of Google Earth as a possible CBRA tool. Following these overviews, the session
included a discussion regarding community needs and research needs for community-based cumulative
risk assessment. Needs identified included: low-cost techniques for community monitoring; methods to
assess the impacts on health following an action; information on nonchemical stressors and vulnerability;
determination of the value of monitoring and modeling results; better methods to quantify local
nonchemical information; tools to characterize dietary exposures at the community level for unique
cultural groups; inventories and protocols for assessing nonchemical stressors; and research that is
directly usable by the community or its local health or environmental department.
The important issues identified by session participants are as follows: (1) Community-driven assessment
is of great importance. (2) Research needs to be usable by communities and their local health depart-
ments. (3) Cumulative risk assessment, including nonchemical stressors and vulnerability, is important.
(4) Researchers should focus on the main contributors to risk and health impacts and recurring
community questions to address cumulative risk. (5) Protocols for nonchemical stressors are needed, and
low-cost measurements are important. (6) Dose-response for risk prioritization is important, including
comparison with other chemical risks and nonchemical stressors. (7) Quantifying benefits is important for
future applications by communities.
SESSION I: DATA NEEDS AND MEASUREMENT METHODS FOR COMMUNITY-BASED
RISK ASSESSMENT
Development of Nanoscaled Sensor Systems for Detecting and Monitoring Environmental
Chemical Agents
Desmond Stubbs, Oak Ridge Center for Advanced Studies
The Oak Ridge Center for Advanced Studies (ORCAS) is a nonprofit organization operating at the Oak
Ridge National Laboratory as a Department of Defense and Department of Energy corporation. ORCAS
is a "think and do" consortium of research universities, government, industry, and nongovernmental
organizations (NGOs) that partners with local educational institutions to perform research. It focuses on
critical issues with strong science and technology content. Problems are framed broadly, taking into
account their scientific, technical, economic, social, and policy dimensions to develop research and inte-
grated strategies for addressing those challenges. ORCAS attempts to ensure that its ideas and research
are translated into action.
The organization held a workshop in April 2006 entitled "Nanotechnology Applications in Environmental
Health: Big Plans for Little Particles" that introduced nanomaterials/nanosensors to the environmental
The Office of Research and Development's National Center for Environmental Research 3
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
and ecological health communities. The workshop explored the "art of the doable" in terms of
nanotechnology and fostered a discussion of the possible environmental health effects, exposure
assessment, and ecological health applications. The result of the workshop was better informed commu-
nities with increased likelihood of beneficial interactions in the future. Additionally, Dr. Michael Strano,
formerly of the University of Illinois at Urbana-Champaign, published a commentary, The Case for
Nanotechnology, which provided a list of wants and needs of nanotechnology researchers, including low-
detection limits, fluorescence-based techniques, and detection technologies based on nanosystems. The
commentary also points out that shelf life varies as a function of the sensing layer, real-time detection is a
common feature of nanosensing technology, and binding mechanisms for the sensor platform determine
useful life of the technology. Following the workshop, researchers determined several factors that need to
be included in a universal system, such as location and activity sensors, an electronic diary, wearable
sensors, and portable sensors.
ORCAS and its partners are conducting research on several devices for use in exposure assessment,
including passive radio-frequency identification (RFID) tags, an electronic nose (i.e., "dog-on-a-chip"),
microelectromagnetic sensors, and interferometric optical sensors. The vapor phase sensor system
currently being researched is a piezoelectric, surface-sensitive device. The surface sensitivity is important
in vapor detection, and the devices can be used in an array to detect multiple chemical agents. In this
system, antibodies to a selected chemical change the three-dimensional signal following detection.
Antibodies are immobilized on gold electrodes as a result of their high binding affinity for the antigen.
The multi-analyte, multicantilever detection system employs arrays of sensors on a single chip with
selective coatings for application-specific programmable sensors. Eighty different chemicals can be
detected on a single chip. An array of 300 chips can be formed on one wafer at a cost of $3 per wafer.
Built-in redundancies in this system allow comparison, and built-in telemetry provides remote sensing
capabilities. The system was tested successfully via a chip implanted in the necks of rats that measured
blood-alcohol levels.
The dog-on-a-chip technology was explored as a method for detecting trinitrotoluene (TNT), because the
ability to detect TNT is key to reducing fatalities from the 100 million land mines scattered across the
planet, tracking explosives materials, and addressing environmental concerns such as water and soil
contamination. Two TNT analogs are musk oil and ammonium nitrate; the Transportation Security
Administration's current methods are unable to distinguish between TNT and the two analogs. ORCAS
researchers used six TNT analogs to perform its proof of concept testing. Three-dimensionally plotting
data points over time consistently and definitively distinguished TNT from the five other analogs. This
method has the potential to be a universal platform to distinguish various analogs and provide useful data.
Discussion
A participant asked which monitoring device would be most useable in the community. Dr. Stubbs
responded that all of the devices are sensitive devices that can be used in the community for acute
sensing, but there is a saturation issue that must be considered with long-term use. The participant asked
if the $3 cost includes tailoring, to which Dr. Stubbs replied yes.
A participant asked if a library or inventory of chemicals that can be detected is available. Dr. Stubbs
responded that an abstract had been published with the inventory, which includes mercury, pesticides, and
explosives.
A participant asked if these devices could be used internally to detect stress steroids and endogenous
chemicals. Dr. Stubbs responded that investigators currently are exploring internal human use. Assays
have been developed but not tested, but this is the direction in which research is heading.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
A participant asked for additional information on technologies that can be used for continuous
monitoring. Dr. Stubbs stated that an algorithm to measure various factors over time can be built into
these devices. Passive RFID tags allow the ability to retrieve data at any point in time. Using array
technology also provides the advantage of monitoring over time; however, difficulties arise as a result of
size and saturation issues. Researchers are working on a way to purge the device to manage these
difficulties. Over-time, near-real-time, and real-time monitoring algorithms can be built into the selective
layer.
A participant asked for comments on the known limits to the technology. Dr. Stubbs responded that as
these are vapor-measuring devices, they are limited by vapor pressure. How analytes in solution are
presented to the device is important. For example, the dog-on-a-chip cannot function in solution, but the
RFID tag can be used in liquid by changing the configuration of the electrode. This, however, causes a
loss of sensitivity.
A participant commented that the ability to detect the presence and the viability of pathogens is necessary
and asked if the research has examined microbial detection. Dr. Stubbs answered that interdisciplinary
research that includes microbiologists is necessary, and there has been some work completed on glyco-
proteins in the cell wall. Chip researchers can collaborate with microbiologists to determine if there is a
marker that can be used to indicate viability.
A participant asked what the ease of use is for the community and if these technologies are appropriate for
those communities exposed to Superfund sites. Dr. Stubbs replied that the objective of developing these
technologies was for this type of exposure. The devices are designed to be wearable, relatively inexpen-
sive, remotely sensed, small, unobtrusive, and without the need for user literacy.
Data Collection Platforms for Integrated Longitudinal Surveys of Human Exposure-Related Behavior
Paul Kizakevich, RTI International
Dr. Kizakevich described research that addresses the need for an electronic diary that was identified
following the April 2006 ORCAS workshop described by Dr. Stubbs. He explained that the need for
integrated data collection is prompted by the various routes and modifiers of exposure. The overall
objective of his research is to develop a personal data collection system that integrates data input streams
for collection of human exposure-related behaviors, supports EPA human exposure assessment models,
can be easily adapted for other human exposure assessment studies, and possesses sufficiently low burden
that most members of the general U.S. household population will be willing to participate in the study for
at least 1 week per season for 1 year. At a very basic level, the approach is to: develop diary method-
ologies for data collection; develop sensors and automation to reduce burden; evaluate methods in the
general population; assess, improve, and enhance developments; reevaluate methods and technologies;
and facilitate system use for future research studies. The researchers are exploring different methods of
collecting data and evaluating these methods by collecting feedback from the population. Four types of
diaries—paper, electronic menu, voice, and photo—are being explored via automated technologies such
as global positioning systems for outdoor location and movement, wireless beacons for indoor residential
locations, wireless Polar chest belts for heart rate monitoring, and accelerometers for movement and
compliance monitoring.
Paper, electronic menu, and voice diaries were used to collect dietary data. Paper and electronic menu
diaries and automated wireless beacons were used to collect consumer product data. For wireless beacon
collection, a fob was assigned to inventoried products; fob-initiated time-stamps were recorded for each
product-use event, and an accompanying electronic (PC Pocket) questionnaire was answered by the user.
The fobs are a low-burden item to collect data, and the Pocket PC was designed with familiar Web-style
menus for ease of use. Additionally, the Pocket PC measures the length of time that it takes users to
operate the Pocket PC. Menus can be tailored to each individual user's activities. The photo diary is a
The Office of Research and Development's National Center for Environmental Research 5
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
passive diary worn on the belt and takes pictures of the wearer's environment every 2 minutes. The user
has the ability to delete photos before uploading to the EPA Consolidated Human Activity Database
(CHAD); CHAD is used to categorize the locations in the photos. Another technology employed is
locator beacons that are placed throughout the residence in study-designated rooms. The locator beacon
syncs with the Pocket PC worn by the user and records the length of time spent in designated locations
within the residence.
A pilot evaluation of the above technologies was employed to evaluate the technical performance of
technologies and systems as well as participant and analyst burden for various diary modes. The study
included 48 participants who for 7 days each used paper, electronic menu, voice, and photo data
collection methods; agreed to heart rate and residential location beacon monitoring; and used wireless
fobs to record product-use events. Participants represented a range of ages and education levels. Dr.
Kizakevich showed examples of activity and dietary data, statistical integration of one individual's
activity for 1 day, the top 15 activities reported by mode, and the top 10 food items reported by mode.
Participant-reported compliance was underreported compared to the literature and may reflect a training
issue. The perceived data-entry burden was greater than actual burden for activity and product-use data
collection but lower for pesticide-use data collection. The data-coding burden was recorded as the amount
of time the analyst needed to code the data.
The researchers concluded that the burden for menu-based activity and location data entry is low;
however, several participants expressed difficulty with the menus. Activity and location reporting were
lower than in previous studies. Participants liked using the voice diary, although technical issues affected
recording quality. Although most participants liked the photo diary, some participants expressed privacy
issues in their workplace. Because some participants reported avoiding activities and limiting diet to
reduce entries for paper, voice, and menu diaries, further improvement in menu structures, prompting, and
automation may help to improve compliance and avoid behavior modifications.
Discussion
A participant asked if the researchers were moving toward a plan to recommend any of these diaries or a
combination of them and if the 7-day data will be available. Dr. Kizakevich responded that the data will
be made available following the next round of monitoring. Originally the goal was to determine the best
method, but now the plan is to release the data and let individual researchers use this knowledge to
determine what method is best for their needs.
A participant asked if any consideration had been given to measuring exposures in children.
Dr. Kizakevich replied that some of the diary methods could be simplified and made very specific for
children. Activity sets can be tailored to children's activities. The voice method, combined with random
prompting throughout the day, is a good method for children.
A participant asked if the resolutions needed to compute exposure for the different approaches had been
calculated. Dr. Kizakevich answered that this had not been done in a formal manner. An advisory panel is
providing guidance for the modeling studies, and this information may be available following the next
round.
A participant asked how easy the sensors were for senior citizens to use. Dr. Kizakevich responded that
this type of information has not been separated out, but one senior citizen who originally was confused by
the technology became one of the best at using it.
A participant asked if a pictorial version would be available for children, those with language differences,
or elderly individuals who cannot see words as well. Dr. Kizakevich answered that this has been
discussed. All menu items are database driven and can be translated easily into other languages. One
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
problem with a pictorial approach is choosing pictures that have universal meaning so that there is no
confusion. The platform is designed to be flexible enough to adapt to the needs of children and the
elderly.
A participant commented that compliance as a function of education level could be investigated. He asked
if there was a problem with care of the devices. Dr. Kizakevich responded that some were dropped, and
battery longevity was a problem.
Assessment Methods for Community-Based Risk Assessment
Elaine Faustman, University of Washington
Three types of studies were examined to understand which pesticide exposures were occurring in
children. The three types of studies were a community-based participatory research (CBPR) project, a
longitudinal multiple sampling project aimed at understanding between- and within-family variability,
and a longitudinal cohort study. The community was a unit of analysis as well as the individual.
Researchers have only crude statistics of organophosphate and carbamate pesticide usage in various
counties in Washington State, whereas the communities have better knowledge of usage. The study
investigated four Washington State counties: Yakima, Benton, Franklin, and Walla Walla. Significant
amounts of organophosphate and carbamate pesticides are applied each year to apples and potatoes, but
the amounts vary each year and are unpredictable.
The CBPR project examined 12 communities, where community is defined as a town or a labor camp.
The project utilized the Environmental Public Health Continuum adapted from Dr. Hal Zenick, which
helps to facilitate understanding of potential sources and how these sources might lead to exposures at the
individual, community, and/or population levels. The Continuum is a framework to educate the public
regarding exposures and risks. Project researchers educated more than 6,000 community members at
more than 250 events, such as community health fairs. Additionally, community members held more than
1,000 home health parties, and the overall number of participants in all levels of community activities was
more than 18,000. Researchers handed out toys to children while teaching them simple things to help
reduce their exposure to pesticides. Second and third grade students were invited to enter a drawing
contest about methods to reduce exposure, and the winning entries were included in a calendar. Children
also were taught handwashing songs. Following the interventions, children were asked evaluation
questions to determine if they were receiving the message.
Another project received crucial input from the community regarding vehicle dust. As a result of the
community's suggestion, the project model was changed, and this greatly improved the study. This under-
scores the importance of involving the community during the earliest planning stages. This project used
chlorpyrifos metabolites as biomarkers of exposure to understand between-person and mother-child
variability. A framework into which factors can be input is necessary to understand this variability.
Quantifiable levels of two or more organophosphates in dust were found in 36 percent of homes and 42
percent of cars, and 60 percent of households (defined as home and vehicles together) had evidence of
two or more organophosphates in collected dust. Results also indicated that 86 percent of children had
quantifiable levels of at least one dialkyl metabolite, and 36 percent had quantifiable levels of both
dimethyl and diethyl metabolites. Evidence of a take-home pathway was determined via the observation
that workers who thinned crops were more likely than those who did not thin to have detectable levels of
azinophos-methyl in their house dust and vehicles, and children of thinners also were more likely to have
detectable levels. Contrary to expectations, workers who reported mixing, loading, or applying pesticides
had lower incidence of detectable pesticide residues in their homes, vehicle dust, and in their children's
urine; this may be a result of mandated safety training for this occupation versus thinners. These data
were compared to National Health and Nutrition Examination Survey (NHANES) data, which showed
that community farmworkers and their children possessed higher urine concentrations of metabolites
versus the NHANES population. Farmworkers and their children also have higher concentrations when
The Office of Research and Development's National Center for Environmental Research 7
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
compared to nonfarmworkers and their children within the same community. Year-to-year and crop-to-
crop variability also existed. The take-home pathways that increased children's exposure to pesticides
were examined so that effective interventions could be planned.
Two longitudinal studies of organophosphate metabolites were used to estimate within and between
variability of 3,5,6-trichloro-2-pyridinol (TCP), the major degradation product of chlorpyrifos and
chlorpyrifos-methyl pesticides. Multiple measurements in the same person across time permit estimation
of both within- and between-person variability. TCP measurements below the limit of detection were
treated as left censored in statistical analyses. Results indicated that this method has a poor ability to
detect exposure to chlorpyrifos and chlorpyrifos-methyl pesticides. Sources of uncertainty for this method
include stochasticity and parameter and model uncertainties. The collection design included three to five
sampling events in each of the thinning, harvest, and nonspray seasons. Genotypes and gene expression
are being examined in farmworkers versus nonfarmworkers and in parent-child pairs. Biomarkers of
susceptibility, exposure, and effect are being determined. A viable framework that integrates these data is
needed to educate the community; the methodology underlying this integrated framework tool is
complicated. Ascertaining the genotype and phenotype for key chlorpyrifos metabolic genes will improve
prediction of exposure response and at-risk individuals in agricultural communities. Determining
polymorphisms is important as well. The community asks simple questions (e.g., Can I eat vegetables
from my garden?) that have complicated answers; experiments must be designed to answer these relevant
public health questions.
Discussion
A participant asked if study participants request and receive individual results. Dr. Faustman replied that
all individuals receive their results with a detailed explanation.
A participant asked how researchers managed more complex questions, such as those regarding risk when
it is not known, and how doctors in the community were involved. Dr. Faustman responded that
pediatricians in the community already are associated with migrant clinics, and there are a lot of
collaborations with community doctors. Study participants who are identified as having life-threatening
conditions or those who researchers feel need follow-up (i.e., those participants whose risk is unknown)
are sent to community doctors.
Dr. Elaine Cohen Hubal, EPA, asked what plans for gene expression had been made. Dr. Faustman
answered that no analyses had been completed, but the profiles will be examined together. In this manner,
variability should be explained and will be approached in an investigative framework.
A participant asked if drinking water was a possible exposure source. Dr. Faustman replied that her
project examined one particular source, but the National Oceanic and Atmospheric Administration
(NOAA) was performing similar studies in drinking water.
A participant asked how much has been done to intervene at different points in the cycle. Dr. Faustman
explained that interventions are set up to educate people to change their clothes before entering their
vehicle or house. The community knows the message, but researchers have not yet worked with the
community to take the next step. The participant commented that the EPA framework can be used as a
resource to assist with the interventions.
A participant commented that the researchers' plan of explaining all biological results could affect the
design of the entire research project. Dr. Faustman explained that it is important to explain the individual
results, and the community knows that the researchers are committed to them.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
SESSION II: THE BIOLOGICAL IMPACT OF NON-CHEMICAL STRESSORS AND INTERACTION WITH
OTHER ENVIRONMENTAL EXPOSURES
Social Stress, Stress Hormones, and Neurotoxins
James Herman, University of Cincinnati
Social stressors do not deprive an individual of essential needs such as oxygen, but these man-made
stressors do affect human physiology. Stress responses can be anticipatory or reactive. Anticipatory res-
ponses are caused by possible threats to homeostasis and involve innate programs and learning. Reactive
responses, caused by direct threats to homeostasis, are generated by reflexive pathways and are true
emergencies. Stress responses are remarkably conserved and can be studied in mammals to construct
meaningful predictions in humans. Behavior systems, the sympathoadrenal system, and the hypothalamic-
pituitary-adrenal (HPA) axis mediate stress responses and release of glucocorticoids. Glucocorticoids are
ligands; therefore, where receptors are present, physiological reactions can occur. These receptors are
ubiquitous in numerous cell types throughout the body.
The HPA stress axis initiates a redistribution of physiological resources, the short-term benefits of which
are energy mobilization and diversion, immune response limitation, and central nervous system (CNS)
arousal. Constant stimulation of the stress response has several long-term consequences, such as
metabolic disease, obesity, musculoskeletal atrophy, hypothalamic-pituitary-gonadal problems, immune
dysfunction, depression, and possibly post-traumatic stress disorder (PTSD). The neurobiological
consequences of stress are numerous. Stress-related affective disease states (e.g., depression, PTSD)
affect 10 percent of the population in any given year. Stress exacerbates other affective disease states,
such as schizophrenia and bipolar disease, and other organic disease processes. Stress hormone secretion
can contribute to cell loss and cognitive decline in aging and dementia.
It is important to note that stress and glucocorticoids inhibit neurogenesis, and social stress produces a
structural change in dendrites, causing them to shrink, in the hippocampus of nonhuman primates. These
observations are consistent with glucocorticoid affects on memory and learning. Additionally, stress
reduces neurotrophic factor expression in the cortex and hippocampus of rodents. Researchers also have
determined that stress experienced by adults is not the only significant factor; stress experienced in utero
can lead to depression-related syndrome. Stress can cause changes in the distribution of types of fat that
affect obesity and diabetes; the percent of visceral fat is increased on recovery from stress. Following
head trauma, glucocorticoids mediate resulting neurological effects; RU486, a potent glucocorticoid
inhibitor, has been shown to be protective. Because stress is a predisposing factor in neurodegeneration,
stress can be considered a risk factor for Parkinsonism. Stress is a predisposing factor in other
neurodegenerative models, including epilepsy, stroke, aging, and Alzheimer's disease. Additionally,
toxins have the ability to modulate circulating glucocorticoid levels; exposure to lead leads to elevated
circulating glucocorticoids.
In terms of stress as a co-morbid condition, the implications for toxicology are immense. Stress enhances
relapse of addictive behaviors (e.g., smoking, alcohol, other drugs of abuse), and social stress promotes
abdominal obesity. Prenatal stress interacts with lead exposure to alter brain neurochemistry, behavior,
and HPA axis drive. Finally, stress represents one of the "hits" in the multi-hit hypothesis of toxicity. In
terms of risk assessment, it is important to note that substance abuse and obesity are prevalent in lower
socioeconomic status (SES) populations, and these populations have disproportionate exposure to some
environmental toxicants (e.g., lead). Environmental toxicants can modulate glucocorticoid secretion,
which in turn enhances neurotoxic processes. Toxins can magnify stress on neurons, and stress can
potentiate the effects toxins have on nerves. Therefore, stress and toxins can initiate synergistic effects on
nerves.
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Discussion
A participant asked if stressors accelerate disease state and aging. Dr. Herman responded that they did,
and they also affect metabolic capacity. Another participant asked what effects result from diet, vitamin
supplements, and exercise. Dr. Herman replied that antioxidants have been shown to be neuroprotective.
Exercise is interesting in that it increases stress on the body while being performed, but decreases stress
between exercise periods. It has been shown to have a number of positive effects on various processes.
A participant asked what measurement limitations exist. Dr. Herman answered that the ability to measure
stress hormones in an at-risk population in real-time is not yet possible. Blood pressure and heart rate
have daily variability and, therefore, are not reliable. Some hormones can be measured in saliva. The
participant asked if baseline variability data are available. Dr. Herman responded that inter-individual
variability is very high, and he is not aware of any available intra-individual data.
A participant asked if the degenerative process can be reversed after stress is removed. Dr. Herman
explained that the best that can be done is to stop the degenerative process; it cannot be reversed.
A participant asked if there are factors that offset stress. Dr. Herman answered that data support that some
factors can buffer some of the negative impacts of stress. Exercise and small natural rewards (e.g., sucrose
snacks) improve the tone of the HPA axis. The participant asked if multiple stress factors worked together
in a synergistic manner. Dr. Herman responded that intensity is a factor, and increased intensity causes
increased wear and tear on the body.
A participant asked what is known about changes in stress response with recurrent acute stress.
Dr. Herman stated that this was examined in a social stress model. Animals experiencing unfamiliar stress
have increased stress response when compared to familiar stress. There is built-in habituation to similar
stress and sensitization to other stress.
Intersections of Social Ecology, Neurobehavioral Development, and Environmental Contamination
Bernard Weiss, University of Rochester School of Medicine and Dentistry
Dr. Weiss displayed a chart of rates of return to human capital investment originally devised by Dr. James
J. Heckman, a renowned economist; this graphic illustrates the finding that an increase of opportunities at
an early age increases benefits during later life, whereas increasing the delay in providing opportunities
for youth decreases benefits. Abecedarian academic outcomes indicate that early investment in children
increases college graduation rates and decreases the rate of children held back a grade. Rodent
experiments showed that enriched environments initiated a change in brain biochemistry and subsequent
behaviors; these enriched environments promote neurogenesis in a variety of ways. An important question
is whether such effects are counterbalanced by exposure to environmental contaminants.
Dr. David Rail, a renowned environmental health scientist, introduced the concept of the overt effect
when he posed the question about whether people would be aware of the toxic potency of thalidomide if
the drug did not have overt consequences and instead reduced affected children's intellectual potential by
10 percent. Today, there are a wide variety of human exposures to neurotoxic agents such as heavy
metals, pesticides, organic solvents, food and cosmetic additives, air pollutants and endocrine disrupters.
Lead exposure is one example of the consequences of not being observant of mounting evidence and/or
placing economic concerns above health. There is a direct correlation between increased blood lead levels
and decreased IQ. Even a small shift in IQ distribution has significant effects on the population, with a 57
percent increase of those labeled "mentally retarded." Research indicates that blood lead increases
reading-level deficits in children, and bone lead increases aggression and delinquency and decreases
attention span. The academic and social costs of lead exposure are high, and from an economic
standpoint, the cost of low levels of exposure to U.S. society has not been measured. It is the lower SES
The Office of Research and Development's National Center for Environmental Research 10
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
groups that bear the brunt of the cost, including increased risk of drug dependency and jail time and
decreased lifetime earnings. Low income has been correlated with increased blood lead levels, lower math
scores, and increased antisocial behavior when compared to those in higher income levels.
One current perspective on lead is that there is no discernible threshold for lead toxicity. Neurotoxic
effects grow more rapidly at low exposure levels, and behavioral disorders are at least as measurable as
IQ deficits. Lead toxicity is a lifetime issue; its effects, including cognitive deficits and osteoporosis,
persist with aging. The appropriate level of concern should be any value above zero, and lead exposure
may diminish the effects of environmental enrichment. Environmental tobacco smoke (ETS) has a similar
effect to that of lead. ETS and material hardship have a synergistic effect on the Bayley Mental
Development Index, and children of mothers who smoked during pregnancy average a 3 percent drop in
IQ. Using 1994 data and extrapolating back to 1964, this drop in IQ translates into a total earnings loss of
$720 billion for those 30 years. Insecticide use and prenatal exposure to poly cyclic aromatic hydro-
carbons (PAHs) also have similarities to lead and ETS exposure. There are commonalities between toxic
exposures and social disadvantage; poverty is linked to high exposures to ETS and PAHs as well as lead
and other developmental neurotoxicants. Social disadvantage embodies multiple dimensions. Income also
affects relative risks of CNS disorders; increases in income and education decrease the effects of affective
and anxiety disorders and substance abuse.
Many of the above issues can be linked to deficiencies in maternal care. Low mother-infant interaction is
a risk factor for both social-emotional competence and verbal IQ in 4-year-old children. Maternal care has
epigenetic consequences. A study on epigenetic changes induced by different styles of maternal behavior
revealed that maternal fostering behaviors are nongenomically transmitted to the next generation of
female offspring; daughters behave like their mothers. Other studies have shown that prenatal stress
increases the effects of lead exposure; some are gender specific and involve altered male sexuality.
Layered, cumulative risks exist in disadvantaged communities that deplete cognitive potential. Small
changes can accumulate and have effects on the disadvantaged community that exceed effects seen in
advantaged communities. A 3 percent rise in IQ would induce reductions in social risks and have enor-
mous benefits on societal outcomes.
Discussion
A participant asked how a proposal to lower the level of concern of lead from 10 |o,g/dL to 2 |o,g/dL would
translate in practical terms. Dr. Weiss replied that one example would be to remove lead-contaminated
drinking water fountains from schools.
A participant asked how to deal with the increasing frequency of potentially contaminated products that
are not being measured before import into the United States. Dr. Weiss stated that stabilizing or
increasing the budgets of EPA and the Consumer Product Safety Commission would be a start.
A participant asked how decreasing the lead level of concern would be beneficial. Dr. Weiss stated that
there is no apparent threshold for lead toxicity.
A participant commented that metals of concern change over time and asked if it would be necessary to
address all metals at the same time to be proactive. Dr. Weiss replied that additional research is necessary
for all metals and other potential neurotoxicants.
A participant asked about the hypothesis that small levels of toxicants are beneficial because they activate
repair. Dr. Weiss explained that depending on the toxin, more negative effects may be seen at smaller
doses than at moderate doses. Lead has no threshold, and alcohol has no fetal threshold. This 50-year-old
doctrine should be re-examined.
The Office of Research and Development's National Center for Environmental Research 11
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Tilson commented that in terms of prioritization, quantifying risks so that communities can make
decisions is necessary. A national calculation may be a good guideline, but some communities will
deviate from this. Dr. Weiss added that disadvantaged communities have increased exposure compared to
advantaged communities.
Social Environment as a Modifier of Chemical Exposures
Robert Wright, Harvard School of Public Health
Construction of the CNS, which begins in utero and continues throughout childhood, involves the
production of 100 billion nerve cells and 1 trillion glial cells; these cells migrate, differentiate, and form
synapses. Glial cells are the primary regulator of synapse formation. Synapses transmit signals between
neurons. Environmental stimuli cause neurons to fire; neuronal/synaptic firing is a signaling process to
mold the synaptic architecture of the brain. The brain builds its network in a partially stochastic manner.
Synapses are made by the billions, and in some respects randomly, between neurons. Net gains in
synapses occur from fetal life until age 2, and then the number of synapses in the human brain begins to
decrease. Synaptic networks are created in a learned process. When synapses fire, neurotransmitters are
released into synaptic junctions, which in turn release growth factors and provide a signal that this firing
is an important neuronal connection; functional synapses release growth factors, whereas nonfunctional
synapses do not release growth factors.
It has been demonstrated that environmental chemicals affect neuronal development. At "low" doses of
blood lead (approximately 5-10 |o,g/dL), lead interacts with protein kinase C and stimulates
neurotransmitter release; therefore, neurons fire in the absence of an appropriate environmental stimuli.
Additionally, lead mimics calcium, a critical component of nerve signal transmission. Calcium enters
neurons during depolarization, but lead blocks calcium channels. The net effect is that lead stimulates
nerves to fire in a more stochastic fashion and also inhibits both appropriate and inappropriate neurotrans-
mission. In this manner, lead decreases the efficiency of the underlying synaptic architecture.
Plasticity is the brain's capacity to diminish the effects of toxic insults through structural and functional
changes via processes similar to synaptic selection. Plasticity allows for new connections to be made that
improve function following an insult. It has been demonstrated that social environment affects neuro-
development as a result of chronic stress that impairs memory and learning capacity. The handling
paradigm of rat behavior illustrates this point; rats that exhibit behaviors that stimulate stress in their
offspring have fearful offspring with a brisk HPA stress response. Although the behaviors tend to cluster
in family lines, researchers determined that environment, not genetics, plays a large role in influencing the
behaviors. Prenatal and early life exposures increase the risk of late-life disease (e.g., hypertension and
obesity), and the handling paradigm is an example of neuroprogramming.
Genes are influenced by histone methylation, which usually turns off genes, and histone acetylation,
which usually turns on genes. Epigenetics refers to heritable changes in gene expression, such as histone
acetylation and methylation, that do not involve changes to the underlying DNA sequences. Epigenetics
plays an important role in synaptic pruning via environmental stimuli, and epigenetic marks within neu-
rons change with synaptic activity. This "epigenetic opening" of synaptogenesis to the environment is
maximal during childhood, and it is the source of the exceptional cognitive adaptability of humans and
possibly the source of its fragility.
A study in rodents examined the effects of social environment and lead. Rats poisoned with lead during
lactation (at levels seen clinically in humans) and kept in social isolation had less memory and learning
function when compared to lead-treated rats raised in groups with social stimulation. This raised a
question about whether reducing stress can be considered a treatment. One study examined mothers' self-
esteem when their children were 24 months old; covariates included blood lead, mother's IQ and
education, and child's gender. The research showed that the effects of lead varied by mother's self-
The Office of Research and Development's National Center for Environmental Research 12
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
esteem; therefore, a positive social environment may mitigate the effects of lead. Another pilot study
investigated in utero ETS exposure and respiratory outcomes and measured exposure to violence (ETV)
and scores on the Wisconsin Card Sorting Test, a neurocognitive test. Children with in utero ETS
exposure and ETV had significantly lower test scores than those without such exposures. This work led to
the establishment of a new birth cohort that will study stress, lead, iron deficiency, and neurodevelopment
from a holistic perspective. The long-term goals of that study are to: (1) identify factors that increase
and/or decrease metal toxicity, (2) understand the biology of metal neurotoxicity, (3) prevent toxicity, and
(4) treat toxicity after it has occurred by finding the appropriate intervention(s).
Discussion
A participant commented on the holistic framework of salutogenesis and the ability of some people in a
normal population to overcome exposures. The positive factors that allow them to do this must be
explored. He asked what Dr. Wright would like to see more of to further this type of research. Dr. Wright
responded that he would like to see Superfund issues considered in risk assessments. Also, society as a
whole can decrease the emphasis on economics. There is no budget for social interventions, but there is
significant funding for pharmaceuticals. This inequality must be overcome.
Dr. Weiss agreed that interventions later in life are useful because neurogeneration still can occur in the
aging brain. It makes economic sense to eliminate contaminants and intervene in cases of contaminated
individuals because the plasticity of the brain is great.
A participant asked how EPA could contribute more to risk assessments. Dr. Wright commented that he
understood that EPA faces budget cuts and undeserved hostility from the community. If enough research
is completed that proves these concepts, the political climate may shift so that there is a mandate for EPA
to receive the resources it needs.
SESSION III: STATISTICAL AND MATHEMATICAL MODELING FOR COMMUNITY-BASED RISK
ASSESSMENT
Community-Based Risk Assessment—A Statistician's Perspective
Louise Ryan, Harvard School of Public Health
Dr. Ryan reported a past case about Cape Cod citizens living near a U.S. Air Force base who were
concerned about excess cancer rates reported on the Upper Cape. There was clear evidence of multiple
exposures, but the number of excess cases was small to moderate, the study power was limited by the
total population, and no individual exposure assessment was completed. The data were very noisy, and
smoothing of the data did not help. It was a very frustrating experience for researchers and the
community. Another home allergen study completed in Boston with mother-child pairs found geograph-
ical variation in maternal serum immunoglobulin E, but geoadditive modeling suggests a "hotspot" in the
city that is confounded by race and poverty. Another study involves cardiovascular response to air
pollution that will attempt to determine exposure levels at various points in the Boston area. The goal of
the study is to relate predicted exposures to health outcomes (e.g., heart rate variability, arrhythmias, birth
weight), and the latent variable formulation is promising. The similarities of these studies include sparse
data, a clever combination of data from multiple sources, and the inclusion of spatiotemporal modeling in
the study designs.
Mercury is an important human exposure of concern. A controversy arose as a result of conflicting
conclusions from two large, well-conducted epidemiological studies. Both studies included prenatal
enrollment, had reliable biomarkers of exposure, adjusted for similar important confounders, and
measured similar outcomes. The National Academies of Science confirmed the quality of both studies and
identified a third. When the focus was shifted from p-values to dose-response estimation, the studies were
The Office of Research and Development's National Center for Environmental Research 13
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
less discrepant. Researchers now are using the data to focus on how methyl mercury relates to IQ because
IQ has been monetized and relates to other endpoints. A summary of endpoints are available from the
three studies and can be divided by domain (e.g., cognition, attention, motor). Graphical representation of
all of the data shows that there is not much commonality between the three studies, but adding additional
endpoints does show some similarities. Random effects formulation was used to express the data as a set
of estimated dose-response coefficients, standard errors, and study and endpoint codes. There are not
enough data to reliably estimate separate study and endpoint variance components, so a sensitive analysis
was employed as assumptions were varied. This showed that one effect of mercury exposure was
decreased IQ. Including the third study's outlying data point made the results appear concordant.
The researchers learned that uncertainty tends to be large when dealing with data collected in real-world
communities, and there is a need to measure characteristics of the community in addition to individuals.
There are major benefits to using statistical techniques (e.g., Bayesian) to synthesize information from
multiple sources. Good tools, such as spatiotemporal and hierarchical models, exist. Researchers must be
cautioned against over-interpreting model results and placing too much emphasis on p-values. Many
sensitivity analyses must be performed. In the future, researchers should fine-tune spatiotemporal models
and initiate work to adjust available tools for combining information so that they are able to handle
multiple scales, levels of accuracy, and so forth. Researchers also should design studies about neglected
topics. One such project is working on developing strategies for ingenious subsampling to maximize
information and minimize cost; another project involves extensions to spatial setting. Spatial design in
general is very interesting; including a spatial and a temporal piece allows space and time effects to be
separated.
Discussion
Dr. Weiss commented that one of the differences between the two controversial studies was that one
examined fish and the other examined whales, which are much more contaminated. The fish study
separated the effects of poly chlorinated biphenyls, and Dr. Weiss asked if it is possible to separate factors
out when they truly are tangled. Dr. Ryan replied that if the characteristics of the studies themselves can
be built, then separation of effects and confounding factors may be possible. If the unit of observation is
the community, then more communities are needed. Hierarchical models, however, do not have the
potential to do this.
A participant asked what was meant by measuring more characteristics of the community. Dr. Ryan
replied that examples would be levels of community violence, racism, poverty, and so forth. The sample
size is related more to the number of communities than to the number of individuals in the community.
A participant asked if data were being collected to validate the model to ensure that the researchers were
not underestimating exposure concentrations and exposures. Dr. Ryan replied that in developing a statis-
tical methodology, agents to test possible underestimation are employed. Her colleagues are beginning to
examine this, and it is a complicated issue.
A Multi-Site Time Series Study of Hospital Admissions and Fine Particles: A Case-Study
for National Public Health Surveillance
Francesca Dominici, Johns Hopkins University Bloomberg School of Public Health
One broad goal of environmental health scientists is the creation of a national system for tracking
population health. Currently, multiple government databases contain substantial amounts of information
on the environmental, social, and economic factors that determine health. Research on population health
could be rapidly advanced by integrating these existing databases and designing new statistical models
that could describe major threats and their causes. These integrated databases and new analysis tools
would create a national system for population health research.
The Office of Research and Development's National Center for Environmental Research 14
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Fundamental research topics regarding air pollution and health include determining if there is a risk at
current pollution levels, how the risk can be estimated, how large the risk is, and what causes the risk. The
objectives of a research project dealing with the health effects of fine air particles are to: (1) assemble a
national database of time-series data for the period of 1999 to 2005 on hospital admissions rates for
cardiovascular and respiratory diseases, fine particulates, and weather for 204 U.S. counties; (2) develop
state-of-the-art statistical methods; (3) develop maps that illustrate relative risk of hospital admissions
associated with short-term changes in fine particles; and (4) illustrate how integration and analysis of
national databases can lead to a national health monitoring system. National data sources include: the
National Claim History Files (NCHF), the Medicare Current Beneficiary Survey, EPA's AirData
database, the NOAA Weather Monitoring Network, and the U.S. Census. The project is examining the
204 U.S. counties for which there are matched data. This national cohort is a national study of fine
particles and hospital admissions in Medicare. Data include billing claims (NCHF) for everyone older
than the age of 65 and enrolled in Medicare, date of admission/doctor's visit, treatment, disease, costs,
age, gender, race, and place of residence (by ZIP code and/or county). The study design includes a large
sample size to identify sample effects. Thus far, researchers have noted seasonality of hospitalization for
chronic obstructive pulmonary disease in Los Angeles, California.
Multi-site time-series studies compare day-to-day variations in hospital admission rates with day-to-day
variations in pollution levels within the same community. The study design avoids the problem of
unmeasured differences among populations, and key confounders are the seasonal effects on infectious
diseases and weather. Semiparametric regressions for estimating associations between day-to-day
variations in air pollution and mortality and controlling for confounding factors are used for within-city
analysis. Hierarchical models for estimating national-average relative rate and regional-average relative
rate and exploring heterogeneity of air pollution effects across the country are used for between-city
analyses. For any given city, the researchers attempt to estimate a small pollution effect relative to
confounding effects of trend, season, and weather. Challenges include the strong role of other time-
dependent factors, the high correlation between nonlinear predictors, and the sensitivity of findings to
model specifications. Results have indicated that all effects are small but consistent across location.
Respiratory data show a lag before the effects of air pollution occur. Determining the mechanisms, size,
chemical components, and sources of particulate matter (PM) toxicity is the next step.
Multi-site time-series studies provide strong evidence of short-term association between air pollution and
mortality, and preliminary results from Medicare data (1999-2002) indicate that current air pollution
levels affect health. It is important to note that national datasets are powerful resources for assessing the
health effects of air pollution, there are statistical models that can integrate information across space and
time, and the national average estimates for the effect of PM are robust to various model formulations and
statistical methods. Researchers need to be able to reproduce previous findings, test assumptions and
robustness of findings, check methodology, and then implement and test new methodologies. One method
by which researchers can share data and advance the science is to utilize the Internet to build databases
and share methodologies from published papers.
Linking national databases and developing statistical methods that can properly analyze them are essential
steps for a successful national public health tracking system. Because of the small risks to be detected and
the large number of potential confounders, single-site studies generally display increased statistical error.
A national system that routinely analyzes data from multiple locations in a systematic fashion is a promis-
ing approach for tracking population health. The explosion of information requires reproducibility and
expertise in statistical methods and integration of complex databases.
Discussion
Dr. Cohen Hubal asked if there are current methods that allow national data to be used to inform at the
community level. Dr. Dominici replied that extrapolation across similar communities is possible.
The Office of Research and Development's National Center for Environmental Research 15
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Cohen Hubal clarified that it is possible to borrow strengths of other characteristics that are more
relevant and asked if at some point community-level data are too sparse to accomplish this. Dr. Dominici
answered that much information may be available in some communities but very little in others. The
choice can be made to extrapolate the data and account for differential variations.
A participant asked if having multiple sites gives power to the data. Dr. Dominici responded in the
affirmative. The participant commented that layers can be added, but it is limited by hospital admissions.
Dr. Dominici replied that this is true, and in terms of linking data together, mortality data also can be
acquired, and geographical resolution can be linked with other confounders. The participant asked if that
meant that statistical methods are built in. Dr. Dominici replied that they were not at this point, but
increased integration makes analysis easier.
A participant commented that this method appeared to work for communities in the range of a population
of 1,000-30,000 individuals and asked what the role is for statistics in a community-based setting.
Dr. Dominici responded that the goal is to be as practical as possible and link only community data with
other available data. The participant asked if it is ever possible to state specifically what factors are
responsible for what endpoints. Dr. Dominici answered that it is possible to address data in one
community by using other community data to increase power. Dr. Ryan added that complexity depends
on what factors are being examined. It is beneficial to reduce citizens' focus on cause and effect, and
instead quantify how much risk people may have. A participant stated that context-driven data still are
needed.
Dr. Cohen Hubal noted that one goal of this workshop is to identify tools and the gap between tools and
answering questions at the community level. It is necessary to be aware of weaknesses and the charact-
eristics of communities that are linked to increased risk of chemical exposure, as well as how more
holistic techniques can be used to determine risks. What types of research can and should be done must be
determined. One outcome of the workshop should be to determine how research can be done to move
forward to answering CBRA questions in a better way.
Risk Assessment/Risk Communication: Understanding the Community
Thomas Schlenker, Public Health Madison-Dane County
Accurate and valid risk assessment cannot be performed unless there is an understanding of the commun-
ity and communication between the community and researchers. A current CBRA involves human
exposure to lead and the associated health risk and will analyze sources, pathways, routes, populations,
internal dispositions, endpoints, and risk metrics. There is an enormous history related to lead, which was
recognized as a risk by Benjamin Franklin more than 200 years ago. There is much research about lead,
and national lead strategies involving EPA and the U.S. Department of Housing and Urban Development
have been successful. Substantial funding is available for lead research.
When communicating with communities, it is necessary to tell a story about the "life" of lead in the body
to engage them instead of merely providing data and scientific jargon about internal disposition about
lead in blood, bone, and the CNS. Community research must involve the knowledge of how people live
and their housing, SES, and behavior patterns. In Milwaukee, Wisconsin, community members and the
media were focused on lead in water, which was a large distraction because researchers were attempting
to focus on other routes of exposure. Policymakers, confused by the media, confounded the problem.
Researchers eventually performed a simple study that indicated that there was no correlation between the
age of the house and lead in water; this allowed them to focus on the issue of lead in paint. It has been
established that increased exposure to lead causes a decrease in IQ; in one cohort, Dr. Herbert Needleman
also determined that children not exposed to lead had a seven times higher rate of high school graduation
than children with lead exposure.
The Office of Research and Development's National Center for Environmental Research 16
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Manganese is considered beneficial in small doses. In Madison, Wisconsin, manganese in water is a
concern because manganese is precipitated out of the water by chlorine and settles into pipes. When there
is a change in hydraulics, the manganese re-enters the water and enters homes as a thick, brown sludge.
Researchers in Madison used the same model to examine manganese as was used to examine lead. EPA's
2003 Health Effects Support Document for Manganese established the health reference level for manga-
nese to be 300 |og/L; in 2004, EPA's Drinking Water Health Advisory for Manganese established a
lifetime health advisory level, which is much more useful as it defined the concepts of short- and long-
term exposure. In the Madison case, one well was perceived as the worst offender in terms of manganese
exposure, but two different wells a great distance from the perceived offender had higher levels of
manganese. Brown water had unsafe levels of manganese, and some clear water with no visible signs of
manganese also had unsafe levels. Additionally, manganese is present in infant formula; foods such as
nuts, grains, tea, and soy; and over-the-counter supplements. The predigested form of infant formula
contains manganese at the maximum health reference level. Human endpoints for exposure to manganese
are generally unknown, but long-term effects are associated with Parkinson's Syndrome and Attention
Deficit Hyperactivity Disorder.
Discussion
A participant commented that models that are developed to bring exposure risks to the community level
must be understood by community stakeholders and asked how researchers can approach the need to take
complicated models and move them into a context where they can be trusted and understood by the
community. Dr. Schlenker replied that providing examples of how it has been or can be used at the
community level would be best. It is helpful to have community guidance and advice. A participant added
that community members do not need to have a technical knowledge of the models to understand the
scientific narrative if it is explained in simple terms. Dr. Faustman noted that helpful guidance is available
to assist in determining what information is needed to answer community questions.
DAY 2: OCTOBER 19, 2007
Perspectives, Issues, and Needs in Community-Based Risk Assessment
George Bollweg, U.S. EPA
This workshop's definition of CBRA is "a model that addresses the multiple chemical and nonchemical
stressors faced by a community, while incorporating a community-based participatory research frame-
work and a transparent process to instill confidence and trust among community members." The National
Research Council's 1996 Understanding Risk was the first well-organized approach to this type of
research. It recognized that not just technical experts perform risk assessment and established steps for
synthesis and implementation. CBRA researchers should consider including an evaluation step at the end
of each research project. The 1997 Presidential/Congressional Commission on Risk Assessment and Risk
Management, Volume 1, identified risk management in addition to risk assessment and stressed the
importance of the problem/context step of the process. The 2003 EPA Framework for Cumulative Risk
Assessment provides a useful, streamlined process. Traditional assessments focused on chemical stressors,
whereas a new focus is population-based assessments, which emphasize that toxicity is influenced by
factors surrounding an individual and not by the toxicant alone.
Different CBRA participants have different needs. Community members need timely answers, whereas
researchers need timely publications. Industry participants need to persuade affected parties that risks are
"acceptable," and EPA managers need to address Agency management priorities. Additionally, state and
regional risk assessors need to conduct credible assessments that address participant needs. Community
assessment can require substantial, multidisciplinary commitment and follow-through. Integrated human
health risk assessments are necessary that combine the various EPA programs having different focuses
and different methods of doing business. For example, the Air Program combines metrics for criteria and
Th e Office of Research and Development's National Center for Environmental Research 17
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
noncriteria pollutant hazards or risk, but some programs may find that combining metrics results in
excessive information loss, hidden incompatibilities, subjectivity, interpretability and communication
problems, false precision, and so forth.
What may be considered "background" exposures are in the foreground for those exposed; fragmented
EPA programs that have a single focus may not consider this. Exclusion of background stressor exposure
or susceptibility results in incremental assessments that are irrelevant to some participants. This can be
solved by addressing site-specific background susceptibility and/or stressor exposures or, if site-specific
information is lacking, deriving a reference human exposure profile to which incremental exposures could
be added.
Methods for choosing participants from the community are needed. Additionally, "getting the right
science" and "getting the science right" are equally important. CBRA problem formulation must include
background (pollutant and/or nonchemical) stressor exposures. What questions the community and the
researchers want answered must be considered during the CBRA planning and scoping process. Organi-
zational and political influences (e.g., levels of review, executive branch process control) on EPA's
Integrated Risk Information System (commonly known as IRIS) productivity should be evaluated; the
levels of review have become too lengthy. The limits of Haber's Rule also must be addressed. In cases
where a community's health is determined to be poorer than national averages but is not addressed in
EPA exposure and toxicity estimates, an epidemiological investigation is necessary. The problem is how
to evaluate this in a CBRA context, and if the assertion is true, how this situation can be addressed.
CBRA research needs to examine synergistic or antagonistic toxic effects, determine the feasibility of an
all-species hazard index, ascertain the appropriateness of using old datasets for future predictions,
establish attributes of successful and unsuccessful deliberative processes, and determine if a formal
evaluation step should be included in EPA risk assessments.
CBRA attempts to address real-world human susceptibility, exposure, and risk with inclusive, often
resource-intensive deliberative processes. Some conceptual approaches and tools are available, but CBRA
needs to process multiple, diverse participant input to better identify and formulate problems; help unify
fragmented disciplinary "silos"; and acquire needed science to address questions and issues of participant
concern.
Discussion
A participant asked what a graph of return on EPA investment in single agents versus mixtures would
look like. Dr. Bollweg responded that he did not know, but it would probably depend on an individual's
needs, as some are exposed to single toxicants and some to mixtures.
A participant asked from a cost perspective whether it is better to create a healthy exposure profile or a
reference exposure profile. Dr. Bollweg answered that the purpose of the reference exposure profile was
to include items that normally were excluded. It is specific to areas and exposures (e.g., dust exposure of
individuals living near roads).
A participant noted that comments from communities near contaminated sites show that the communities
instinctively understood that their present condition is not good in terms of health and wellbeing. He
asked whether Dr. Bollweg purposely excluded the need to satisfy regulations and laws from his presen-
tation. Dr. Bollweg replied yes, because although difficulties have arisen as a result of permit
requirements, the situation, especially with Superfund sites, is improving. There is a need to satisfy the
goal of the Superfund as well as the conflicting needs of the community; CBRA may be able to integrate
these differing needs.
The Office of Research and Development's National Center for Environmental Research 18
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
A participant commented that local health departments need to be involved in CBRA projects and asked
how to go about securing their participation, as well as the participation of other agencies. Dr. Bollweg
answered that resource commitment is important. Also, determining the availability of data is important
because some agencies are not authorized to share some data. Prior knowledge that obtaining information
is a complex and complicated process may decrease frustration.
Overview of Breakout Groups
Yolanda Sanchez, Association of Schools of Public Health (ASPH) Fellow, U.S. EPA
Ms. Yolanda Sanchez reiterated the definition of CBRA that Dr. Bollweg introduced in his presentation.
The three breakout session themes follow the three session topics of the previous day: (1) data needs and
measurement methods for CBRA, (2) biological impact of nonchemical stressors and interaction with
other environmental exposures, and (3) statistical and mathematical modeling for CBRA. Each breakout
group should: (1) identify tools and approaches that may be applied to conduct CBRA, (2) discuss how to
incorporate community-based information into traditional EPA risk assessments, and (3) evaluate the
research needs for CBRA. To facilitate dialogue in the breakout session, the organizing committee
produced charge questions that have been included in the workshop materials.
CONCURRENT BREAKOUT SESSIONS
Breakout Session 1: Data Needs and Measurement Methods for Community-Based Risk Assessment
Moderator: Elaine Cohen Hubal, U.S. EPA
Recorder: Jennifer Hurlburt, The Scientific Consulting Group (SCG), Inc.
Attendees: See Addendum
Dr. Cohen Hubal showed slides depicting two different conceptual models and a list of vulnerability
factors to help facilitate thoughts about data needs and measurement methods. Important questions for the
group to address are: (1) Are there data currently available? (2) What are the data sources? (3) When is it
necessary to collect data in the community? (4) What are the characteristics of the environment and of the
individual environmental indicators that researchers must consider?
One issue that is confusing to many, including scientists and those conducting assessments, is how to link
individual-level environmental exposures to community-level factors. The actual assessments are
conducted on the individual level, but one method to connect the two is to group the individuals together
for the analysis of the community-level factors, as they were in the distribution curves from Dr. Faust-
man's study.
Dr. Faustman asked Dr. Cohen Hubal about the Conceptual Model for Considering Vulnerability in
Cumulative Risk Assessment. She wondered about the best method to incorporate the information from
Session II: The Biological Impact of Non-Chemical Stressors and Interaction with Other Environmental
Exposures into this type of model. For example, where do the potency factors enter for a given stressor,
whether it is chemical or nonchemical? Dr. Cohen Hubal responded that that particular model was not
intended to represent exposure length. The model's focus was on classification of all of the different
factors; there are many issues (e.g., temporal aspects) that must still be addressed in the study.
Mr. Matthew Lakin, EPA, spoke about the distinction between vulnerability and susceptibility. One
school of thought is that vulnerability and susceptibility are two different things. Susceptibility includes
the biological factors that make a person more predisposed to some type of effect or adverse outcome.
Vulnerability includes the environmental characteristics that might lead to a higher level of exposure.
These appeared to be only one category in the displayed conceptual model. Dr. Cohen Hubal explained
that in that particular study, susceptibility was categorized as a vulnerability.
The Office of Research and Development's National Center for Environmental Research 19
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Alesia Ferguson, University of Arkansas for Medical Sciences, mentioned that a speaker the previous
day had mentioned a theory related to resilience. Would resilience be considered a vulnerability or a
susceptibility? Mr. Kent Thomas, EPA, answered that resilience would be considered a susceptibility.
Resilience occurs on two levels: (1) at the individual level, resilience is lessened as a person ages, so
repeat exposures may be more harmful to older individuals; and (2) at the community level, the
community as a whole may have less resiliency to recover from exposures. Dr. Cohen Hubal explained
that in her study susceptibility was defined as genetic susceptibility or developmental stage susceptibility.
She explained that researchers traditionally have studied the source-to-outcome paradigm, but this breaks
down when multifactorial issues are examined. She maintained that researchers need to move from a
pathway focus to a focus that includes other issues that are present with these exposures. Dr. Faustman
did not agree that the framework necessarily breaks down with these issues. She has worked with
engineers who use some interesting vulnerability diagrams, and many issues are involved. For example,
community location or conditions are important factors. Dr. Cohen Hubal commented that a researcher
could define a system as a community and then specifically examine particular individuals or particular
sources, depending on how the boundaries are drawn. If the intent is to identify multiple factors, the
researcher must draw the boundaries to ensure that all the inputs and outputs are considered.
Dr. Cohen Hubal explained that she presented the conceptual models as examples to stimulate discussion.
What are the important factors at the individual and community levels? Mr. Thomas explained that four
categories of data are needed for a cumulative risk assessment: (1) physical environment, (2) social
environment, (3) chemical environment, and (4) health (as an outcome or as a risk factor). Dr. Ferguson
asked if data needed to be defined to represent risk quantitatively. Mr. Thomas replied that in terms of a
screening-level assessment, researchers are able to determine some of the major stressors in the
community. The next step is to work toward understanding the relative risk associated with these
stressors.
Dr. Cohen Hubal asked if the participants knew of publicly available data that could serve as a starting
point for researchers. Dr. Danelle Lobdell, EPA, responded that the data available depend on the research
question and on the community. Dr. Faustman asked if any of the participants knew of an example of a
known stressor other than air pollution that had been linked to specific communities. Dr. Dina
Schreinemachers, EPA, replied that data on various toxicants are available in four states. She suggested
that researchers start with ecologic studies and then move to subject-based studies. A series of multilevel,
multidisciplinary studies is needed. Dr. Faustman mentioned that the CDC conducts surveillance projects
in partnership with universities across the country. Dr. Socoby Wilson, University of South Carolina,
added that he recently submitted a proposal to EPA to develop national health indicators.
Dr. Cohen Hubal asked those with experience working in communities if they often found the data they
needed when they began their work. She asked for examples of the types of data found and whether the
data were general or community-specific. Are there efficient, cost-effective ways to obtain these data?
Dr. Ferguson responded that it depends on the chemical of interest and the location. For example, some
states collect extensive lead-related data, whereas others collect no lead-related data. Mr. Thomas
suggested that researchers start by determining the community's data needs. The next step is to determine
what data are available. Dr. Mari Eggers, Montana State University, added that it would be helpful if
there were guidelines detailing where different types of data could be found. Mr. Lakin said that he and
his CARE Program colleagues currently are drafting guidelines, but there are a lack of data on many
topics, and even if data exist, access often is an issue. Dr. Ferguson suggested that data be extrapolated
from one community to another. Mr. Lakin added that this approach would involve quantifying the
differences between the communities (e.g., accounting for a higher smoking rate in one community). Dr.
Faustman suggested compiling a list of available data. Mr. Lakin agreed that a list could be helpful but
added that the ultimate goal is to identify quantitative relationships. Dr. Ferguson mentioned the study
conducted by Dr. Zartarian as a potential model; Dr. Zartarian and her colleagues identified 100 factors
and performed a stacked quantitative analysis. Dr. Wilson suggested developing spatial indices. He
The Office of Research and Development's National Center for Environmental Research 20
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
mentioned some other potential models, including the social vulnerability index and a project in
California related to risk and environmental health disparities. Mr. Lakin noted that there still is difficulty
in linking the information to environmental risks.
Dr. Wilson pointed to the importance of collecting qualitative data as well as quantitative data.
Quantitative data alone will miss many important issues, such as the effects of living in a stressful
environment. Mr. Lakin agreed that there is value in both quantitative and qualitative data. Mr. Thomas
noted that people often do not understand the risks associated with environmental stressors. The perceived
risk might be very different from the actual risk. Dr. Ferguson pointed out that perceived risk still is very
important, and Mr. Thomas clarified that he was not discounting perceived risk. Dr. Pamela Rao,
Farmworker Justice, commented that, as a social scientist, her work always begins with the people in the
community; their perceived risks are the starting point. Mr. Lakin asked Dr. Rao if she thought better
information on community cohesion, sense of identity, and other factors linked to perceived risk were
needed. She agreed that better data are needed and emphasized the importance of starting with qualitative
data; without qualitative data the work will have no direction.
Dr. Cohen Hubal asked the participants to share their thoughts on measurement methods. Dr. Faustman
commented that GIS data are very useful. GIS data can be used to ensure that areas are not missed in risk
assessments. Alternatively, researchers need to be careful when using these data to determine specific risk
areas. For example, a 1-mile radius might be identified as an area of concern, but what about the people
living just outside of that 1-mile radius? Dr. Wilson pointed out that this is where the qualitative data is
useful. Dr. Rao emphasized that research cannot be performed at a distance; it must be done in the
community.
Dr. Ferguson asked if there is a point at which there are too much data. Mr. Lakin thought that a better
question might be: What is the right amount of assessment? In his work, Mr. Lakin has found that the
answer depends on the community. Dr. Cohen Hubal added that the information collected would be based
on the community's concerns and conditions present in that community. Dr. Rao suggested starting with
the research question. Mr. Thomas pointed out that from EPA's perspective, the question is: Where does
the chemical and biological pollutant risk fit into that context? Mr. Lakin stated that it would not be
inappropriate to begin a risk assessment by focusing on specific chemical stressors; that can be one of the
solutions offered to the community, and if the community identifies other problems, others can be brought
in to address those issues.
Dr. Faustman warned that risk comparisons can be dangerous. It is important not to ease the pressures on
industry; they are responsible for keeping the environment clean. Dr. Cohen Hubal noted that there are
still many compounds in the everyday environment about which little is known. Dr. Lobdell offered lead
as an example; it is still not known if any level of lead in the blood is safe.
Dr. Faustman gave an example of a multifaceted problem that would require a multidisciplinary
approach: the loss of traditional diets in Native American communities. This loss has resulted in serious
health problems for this population. Loss of salmon, a staple of the Native American diet, from the
waterways has contributed significantly to this problem. This loss can be represented with data. One
aspect of improving the health of Native Americans involves ensuring that the waterways are clean to
allow salmon to thrive. This problem requires that various agencies work together.
Mr. Thomas noted that some of the studies presented the previous day had indicated that the effects of
exposure could be magnified because of certain attributes and vulnerabilities. What data are needed to
understand those vulnerabilities? Dr. Rao asked if he was referring to taking the analysis to the chemical
or environmental level. Mr. Thomas clarified that he was referring to the understanding that in a
community there are multiple risks, and many of them have little to do with chemical and biological
exposures.
The Office of Research and Development's National Center for Environmental Research 21
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Cohen Hubal asked Dr. Rao about a comment she had made earlier about the difficulty of measuring
and characterizing the location of certain groups (e.g., migratory farmworkers) and their related risk.
What are the limitations? What measurements are needed? Dr. Rao clarified that she was referring to
cumulative risk issues that are not dependent on the individual's geography. Given that, Dr. Cohen Hubal
asked how a researcher could define, track, and characterize the community. What should be measured?
Dr. Rao responded that in many cases the data needed are not readily available. In her work with
pesticides, she and her colleagues have had to use sales records and other clues to gain a better
understanding of farmworkers' exposure. Dr. Wilson noted that different data are available on the
national and local levels. The CDC has performed much work collecting environmental public health
data, and EPA has state-level environmental indicators in areas such as air and water. Dr. Wilson added
that the data frequently must be collected at the local level.
A participant asked if there were any case studies of comprehensive cumulative risk assessments that
could be used for guidance. Dr. Faustman replied that there are some good examples, including
Community Risk Profiles and Understanding Risk. Dr. Ferguson commented that as the risk assessments
become more advanced, multidisciplinary approaches are needed. Mr. Lakin commented that, from a
research needs perspective, taking a community-based participatory research approach is one method by
which to ensure a multidisciplinary approach. He stated that more demonstration projects are needed to
advance the work in this area. Dr. Wilson mentioned a book called Street Science by Jason Corburn that
includes examples of community groups using EPA's exposure risk model.
Dr. Schlenker explained that most of his work involves starting with a health outcome and moving
backward to find the cause. For example, in Madison-Dane County, as in the nation as a whole, the infant
mortality rate (the rate of infant deaths occurring before age 1) for African Americans was more than
twice the Caucasian rate. Since 2000, however, the African American infant mortality rate has steadily
decreased in Madison-Dane County and is now comparable to the rate for Caucasians. What changed?
Dr. Schenkler said that answering that question would involve qualitative research comparing the African
American mothers currently in Madison-Dane County to African American mothers in other counties or
comparing them to the group of mothers experiencing the high infant mortality rate.
Mr. Lakin mentioned the public availability of certain data, such as the mapping information available
through Google Earth. The availability of this information makes it more difficult to mislead the public,
but there still is a need to further expand these types of tools in terms of community access to data and
interactivity. Dr. Faustman cautioned that with the current accessibility of certain data, researchers must
be careful to protect people's privacy. In one case, for example, breast cancer data were mapped by house
in a neighborhood, allowing everyone in the neighborhood to see who did and did not have breast cancer.
Mr. Lakin thought that address-level data could be very useful in risk assessments.
Dr. Lobdell reminded the group that risk assessments must take into account the realities of the people
living in those areas. For example, a factory may be a major polluter, but if the livelihoods of the people
in that area depend on that factory, they may not want to address the pollution problem for fear that they
might lose their jobs. Dr. Wilson added that many people do not have any other employment options.
Dr. Faustman emphasized that communities should not feel as if pollution control is their burden; it is
industry's responsibility. Dr. Ferguson said that for health outcomes, it is known that multiple stressors
can contribute to health outcomes, even independent of one another. Thus, a chemical stressor could be
removed, and the community could still have the same health outcome. If EPA finds that the chemical
stressor is not the major problem in a community, then other agencies will need to be involved.
Dr. Faustman suggested that other agencies be included from the beginning. Mr. Lakin pointed out that
EPA's Ecological Program focuses on many of these multifactorial issues (e.g., how urban sprawl affects
the environment); much of this work is performed in partnership with other agencies.
The Office of Research and Development's National Center for Environmental Research 22
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Wilson suggested using the environmental justice framework. He gave an example of a community in
North Carolina that blocked the building of a highway by submitting a complaint to the Department of
Justice arguing that their civil rights would be violated if the highway was built because they would not
be able to access basic amenities. Are there other innovative approaches like this that could be used to
affect change? Mr. Lakin agreed that this was one way to approach the problem. He asked what the
research needs are. What is the missing component in terms of current scientific understanding?
Dr. Wilson responded that, in this case, the community performed its own cumulative risk assessment.
Mr. Lakin encouraged the other participants to think about ways to reproduce this type of success story in
other communities.
Breakout Session 2: The Biological Impact of Non-Chemical Stressors and Interaction With Other
Environmental Exposures
Moderator: Carrie Knowlton, ASPH Fellow, U.S. EPA
Recorder: Kristen LeBaron, SCG, Inc.
Attendees: See Addendum
Ms. Knowlton explained that the group's first charge was to identify tools and approaches that could be
applied to CBRA. Mr. Gary Bangs, EPA, noted that some researchers have obtained access to difficult-to-
access datasets. Perhaps a preconstructed, integrated database could be made available by those
researchers who have broken barriers. Mr. Ravishankar Rao, EPA, added that Census data could be
included. Ms. Kathy Sykes, EPA, mentioned the Interagency Forum on Aging-Related Statistics and
noted that there may be a parallel dataset with families and children. Mr. Michael Callahan stated that
there are many data in the literature about stress-causing impacts, the effects of violence on asthma, and
other topics that EPA normally does not study. Dr. Robert MacPhail, EPA, agreed that there is a
significant amount of data on psychoneuroimmunology topics.
Ms. Kacee Deener, EPA, asked if data on biological stressors or social stress in combination with
environmental stressors were available. Dr. MacPhail responded that data on both, but primarily on
biological stressors, existed. Ms. Deener asked if data on toxins other than lead were available. Dr. Peter
deFur, Virginia Commonwealth University, commented that other toxins were included in a background
paper.
Mr. Rao noted that some common data are available that may address community concerns. Mr. Bangs
shared Mr. Callahan's concern that the right data may not be considered, and some data related to
stressors, housing, measurement endpoints are not necessarily found in PubMed. Dr. Weiss stated that the
number one factor in health risk is poverty.
Ms. Knowlton asked participants to identify models and technologies in addition to data sources.
Mr. Michael Wright, EPA, suggested an examination of group-level effects separate from individual-level
effects. Mr. Callahan noted that the Tool for Health and Resilience in Vulnerable Environments, an index
of social capital commonly known as THRIVE, is one available tool.
Dr. deFur asked if models in this context were defined as computer-predicted or conceptual.
Ms. Knowlton replied that she interpreted the question as computer-predicted, but conceptual models
could be considered if necessary. Dr. Robert Hubal, RTI International, explained that one possible method
is high-performance computing that simulates community impacts after an event. Dr. deFur added that
some comparative behavioral science technologies may be useful, as well as some in the strict ecological
sciences. Behavioral science may be a closer topic area that will not necessitate too many interpretations.
Dr. MacPhail asked if the ecological science technologies were nonhuman-based. Dr. deFur responded
that this was the case and that he was referring to the topic of experimental ecology in which the science
examines large animal populations and ecosystems that have population changes as a result of stress
(e.g., fragmentation of the ecosystem). These data can be indirectly translated into human systems.
The Office of Research and Development's National Center for Environmental Research 23
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. MacPhail commented that field research provides the opportunity to perform mesocosm studies and
gain control over stressors. Dr. deFur agreed that mesocosm studies have potential.
Mr. Bangs asked if social coping models were available that examined the addition of stressors and what
factors lead to a failure or breakdown of coping at either the individual or the community level. Dr. Weiss
stated that there is a large amount of information in medical and social science literature about the effects
of stress on behavior and biology, but there are very few islands of data that have examined the joint
effects of these types of displacements and chemical exposure.
Mr. Nigel Fields, EPA, commented that not many researchers were working on these types of effects. He
mentioned the Broken Windows Theory, which explores social problems in the community that increase
stress, and the Weber Theory, which states that African American women over time experience different
impacts on their health than women of other races, and these impacts affect their children as well. There
are a number of social models and theories that can be explored.
Dr. Weiss noted the difference between health and conceptual models. A given population has certain
parameters and then is stressed by a chemical exposure; the biological basis for this effect has not been
examined. This is a whole new field. He cited the example of a Montreal group that is examining an
epigenetic model and maternal exposure to chemicals.
Ms. Knowlton summarized that social and environmental information need to be integrated. Dr. deFur
commented that much of the research is attempting to address different questions. Dr. Weiss stated that
the research addresses nonchemical stressors that are not usually considered by EPA. Mr. Bangs
described a workshop in February 2007 that discussed microbial insult of nonimmunocompetent
individuals and how these individuals respond. Dr. deFur described work that examines specific
contaminants, how the contaminants affect community by source, and how disease affects response.
Dr. MacPhail noted that the stress experienced by home caregivers has not been examined and this
phenomenon will increase over time. It is possible that environmental factors could be involved. Stress
could result in accelerated aging in the caregiver. Ms. Sykes added that premature death also could be a
result.
Mr. Ross Highsmith, EPA, added that epigenetic studies could be added to the toolbox. Mr. Wright
suggested that simulation-based techniques and approaches across disciplines could be included.
Ms. Debbie Lowe Liang, EPA, asked if there was a deadline for providing suggestions and input to EPA
about these topics. Ms. Deener responded that EPA would accept input for the next month. Ms. Liang
asked if input from individuals who did not attend the workshop was acceptable. Ms. Knowlton
responded that is was.
Ms. Knowlton moved the discussion to the second charge question and asked the group to consider how
CBRA could be added to traditional EPA risk assessments.
Ms. Deener stated that the community can be important in identifying the exposure pathway.
Ms. Sanchez, ASPH Fellow, added that the community also can identify exposure sources. Dr. Highsmith
commented that they can describe lifestyles that may be outside of expectations. Mr. Wright noted that
unique diets could be identified by the community. Ms. Liang stated that community input regarding
social stresses is important.
Dr. deFur noted that several methods are presently in use at EPA. The 2003 EPA Community
Involvement Conference, which might have identified successful methods regarding community focus
The Office of Research and Development's National Center for Environmental Research 24
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
groups and meetings, could be a potential resource. Existing social structures (e.g., church) can be used as
a gathering tool to obtain community input.
Dr. Weiss described a Web-based system for CBRA that he developed 10 years ago as the result of an
EPA initiative. The reference for the resulting publication is: Weiss B. A Web-Based Survey Method for
Evaluating Different Components of Uncertainty in Relative Health Risk Judgments. Neurotoxicology
2001;22(5):707-721.
Mr. Fields cited the Casa de Salud in Massachusetts as an example of building community infrastructure
and knowledge. Researchers worked with the community and set up house parties to address household
chemicals and asthma. It took approximately 3 years to escalate, but it has become a significant health
movement about a variety of health topics such as diabetes, HIV/AIDS, and so forth. The mayor has
incorporated it into the city's mainframe. Originally, this was a large, disenfranchised population that did
not know how to be included but has increased its involvement. Additionally, Drs. Barbara Harper and
Anna Hardy are exploring nontraditional routes of exposure during religious rites.
Dr. MacPhail asked if the group's definition of community included a cross-section with all ages, races,
gender, education, and so forth represented. Mr. Callahan indicated that this was not necessarily the case.
Mr. Bangs stated that the community of interest includes affected individuals, and this might be a very
specific group. Dr. deFur added that geography might be one classification.
Dr. Weiss advised that the term community must be defined. He is involved in a community advisory
board that has varied members from industry, academia, and county health, who cover all constituents of
the community. The community provides input so that the board can determine their environmental health
needs. EPA could construct a paradigm in which community representatives are approached and included
in an advisory board. Dr. deFur stated that EPA facilitates such committees at cleanup sites. Ms. Sanchez
asked if Superfund sites were included. Dr. deFur stated that cleanup sites include both Superfund and
non-Superfund sites, as well as states mandated with the Comprehensive Environmental Response, Com-
pensation, and Liability Act (commonly known as CERCLA). There has been mixed success with this
approach, and he is not aware of any studies regarding why certain attempts succeed or fail.
Ms. Knowlton asked participants to consider how the information obtained from the community can be
used.
A participant asked about the CARE Program. Ms. Knowlton replied that the CARE Program provides
communities with tools to determine their most important stressors and technical assistance to implement
programs to reduce their own environmental problems. It does not use traditional risk assessment
methods.
Mr. Callahan stated that if new information (i.e., community input) is being placed into an old framework
(i.e., EPA traditional risk assessment process), then stakeholders and researchers must determine a
method to make EPA decision-makers realize that it is in their best interest to consider it, or this will not
happen. Dr. deFur agreed that this problem must be solved at the beginning; the same holds true for
motivating the community. The inertia of encouraging citizens to be involved and inducing decision-
makers to care must be overcome. Dr. Weiss suggested identifying community members who are active
and approaching them. Mr. Callahan stated that decision-makers need a reason for change to happen; this
is how to attract them.
Dr. Hubal stated that specific, real-time data can be gathered from individuals in the community; EPA
managers can be shown the real-time data to drive policy decisions that need to be made. One method
may be an interactive survey. Dr. Highsmith cautioned that some individuals and communities have been
oversurveyed. It may be possible to find people in the community who have better questions.
The Office of Research and Development's National Center for Environmental Research 25
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Ms. Deener suggested increasing the level of trust between communities and EPA. Dr. deFur agreed that
researchers must know the community, or the whole effort will fail. Mr. Fields added that understanding
the linkages and social cohesiveness is necessary. Some communities provide services and support for
each other; these services make the group functional. It is necessary to characterize the connections and
know who provides what services to whom. Dr. deFur summarized this as assessment of social capital.
Mr. Bangs stated that the needs of the EPA risk manager and the needs of the community must be
satisfied, or the effort is a failure.
Dr. deFur suggested changing and reshaping the risk management process so that it is not so rigid and
stepwise, so that new types of information or processes can be inserted. Currently, the process does not
work if it becomes necessary to work backward. The source-to-outcome paradigm cannot be used because
the research is not starting with the source.
Ms. Knowlton asked the group to consider ways that this discussion could be expanded to include
nonchemical stressors. Dr. Weiss stated that nonchemical stressors have biological effects. This can be
the baseline with which to start. Having national standards that may not apply to all communities is not
effective. Some communities will be more susceptible because of current health standards. Ms. Sanchez
commented that within the environmental justice movement the issue that equal exposure does not equate
to equitable exposure has been argued for more than 15 years. Dr. Weiss wondered if it had been argued
on a biological basis.
Mr. Bangs replied that a common complaint is that there is no metric. Ms. Sanchez thought that
Dr. Faustman currently was involved in a water quality standards decision that affects a tribal community
and whether or not the community should have lower standards because of their lifestyle. Mr. Bangs and
Dr. deFur asserted that the states of Oregon and Washington had lowered standards; there is a precedence
for this type of decision based on community lifestyle.
Dr. MacPhail stated that local newspapers have good knowledge of their own community. They are able
to collect and disseminate information that might be useful.
Dr. deFur commented that a review board, comprised of community members with local knowledge,
needs to be instated because local knowledge can be a modifier of quantified data. The local community
might have a different perspective than what statistics indicate. Mr. Fields agreed and cited the example
of a community in which political leaders did not know the practice of Santeria existed; the practice was a
source of mercury exposure that would have been otherwise unknown without local knowledge.
Ms. Liang commented that the technique might not work with national standards, but community
advisory boards could help EPA determine the most impacted communities. Dr. MacPhail agreed that
these boards could help identify at-risk communities, but they will not be able to help researchers
understand why the communities are at risk; that is a scientific question. Mr. Callahan stated that com-
munity knowledge often is surprising. Ms. Knowlton added that community members know their own
health and nonchemical stressors. Dr. MacPhail said a distinction between "identify" and "understand"
must be made.
Ms. Knowlton asked the group to consider the third charge question, which asks participants to evaluate
research needs for CBRA.
Dr. Highsmith stated that many factors result in stress. The two questions to consider are: Is there a
relative potency of stress? What is the relevance of stress to susceptibility? Susceptibility appears to be
an issue because it changes how exposures affect susceptible individuals. Mr. Callahan thought that by
The Office of Research and Development's National Center for Environmental Research 26
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
taking the approach of relative potency, it is similar to saying that stress is a carcinogen. A different
approach must be taken.
Dr. deFur stated that there are decades of clinical and laboratory research on stress response. The largest
gap is that no one has asked questions that are specifically applicable to the issues being discussed. Data
about stress and about certain environmental contaminants are available, but there are no data regarding
how to combine this information or about what factors make individuals or groups more vulnerable. The
question of vulnerability can be answered indirectly by gathering data from the individual parts and
overlaying or combining them. The research question that has not been asked is what makes individuals
in the community more vulnerable; in this regard, community is defined geographically or demograph-
ically. He thinks of vulnerability as a specific exposure concentration and of susceptibility as having a
biological basis. Dr. Highsmith clarified that vulnerability means sensitivity and that susceptibility is a
biological term. Mr. Callahan responded that the 2003 Framework for Cumulative Risk Assessment
defined vulnerability, susceptibility, and sensitivity. Sensitivity and susceptibility are biological, whereas
differential exposure, differential ability to recover, and differential preparedness are not.
Dr. deFur commented that social capital can crumble as a result of changes in infrastructure; therefore,
this is one topic that can be considered.
Ms. Deener asked about the usefulness of laboratory animal studies versus community or epidemiological
studies. Mr. Callahan replied that epidemiological studies in small communities are not useful because
there is not adequate power. What is needed is a combination of laboratory research and community
studies. Dr. MacPhail stated that the most beneficial features of laboratory research are the ability to con-
trol stressors and to collect tissues and other samples. Stress markers in the brain can be linked to urine
and blood, which in turn can be linked to the community.
Dr. Hubal commented that the military is studying PTSD in returning soldiers; this could be a potential
source of data. This is a specific community that can be studied, and laboratory data are available because
the military is starting to collect them. Dr. MacPhail added that the military is collecting baseline,
predeployment data so that comparisons can be made. This community is exposed to many stressors, so it
might become too prohibitive to study all of them. Dr. deFur stated that the myriad of combinations also
makes it prohibitive.
Dr. MacPhail stated that it is necessary to have a simplified design that can measure complex systems.
Ms. Knowlton asked the group to consider the second part of the charge question regarding important
methodological gaps for incorporating nonchemical stressors into traditional EPA risk assessments.
Mr. Bangs commented that a holistic approach is needed. Ms. Deener speculated whether a discussion
about incorporating nonchemical stressors into traditional EPA risk assessments can occur if the basic
questions are not known. Mr. Fields commented that one gap includes determining what amount of
epigenetics and other research will be studied before moving into the community.
Dr. deFur stated that research that tests assumptions is needed, especially the source-to-outcome
paradigm. Mr. Callahan commented that the cumulative risk paradigm does not use the source-to-
outcome paradigm, so this does not need to be addressed. Research is needed to determine which
chemical stressors are important. Dr. MacPhail asked if a ranking for stressors had been investigated.
Dr. deFur replied that such a ranking was published in the May 2007 issue of Environmental Health
Perspectives. Ranking items such as psychosocial factors could change the quantification component or
increase efficacy at the receptor level. Ranking also can change the dose-response curve in many ways
that could result from vulnerability. There is no mathematical distinction between the ability to respond
and the ability to recover, but there is a biological difference.
The Office of Research and Development's National Center for Environmental Research 27
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Mr. Bangs commented that basic biological and epigenetic research about multistressors, as well as a
more ecological approach to risk assessment and risk management, is needed. Mr. Callahan agreed that
this is how cumulative risk assessment must be done. Dr. deFur commented that specific ecological
activities must be considered, and eventually cumulative risk must be a combination of both human health
and human ecological risk assessment.
Mr. Callahan stated that there must be a plausible link between cause and effect (i.e., more than random
data) for decision-makers to act. Dr. MacPhail added that regulators must realize that this is an exceed-
ingly complicated issue.
Breakout Session 3: Statistical and Mathematical Modeling for Community-Based Risk Assessment
Moderator: Pasky Pascual, U.S. EPA
Recorder: Mary Spock, SCG, Inc.
Attendees: See Addendum
Mr. Pasky Pascual thanked participants for attending the session and asked them to introduce themselves.
After the introductions, he noted the need to formalize and quantify data for use in decision-making.
There should be a difference between the analytical component in the model and the modeling form itself,
because the latter is what informs communities about their risks. If the modeling form is transparent,
community members can follow the narrative of the science without needing to understand the analytical
component behind it. Duke University is conducting interesting research in this area and has produced
very simple, accessible modeling forms that lay people can understand, despite the sophisticated set of
analytical techniques behind the models.
Dr. David Reif, EPA, agreed that it is important to present data to communities in a manner that does not
involve excessive technical language. How a solution to a problem is represented is more important than
the underlying method used to reach the solution. One approach is to use easily accessible infographics,
maps, graphs, and pictures.
Mr. Pascual suggested that the HB Model is a ready answer to the first question, which asked participants
to identify tools and approaches that could be applied to CBRA. Mr. Schultz responded that HB is a tool
that works well for spatial representation of levels but does not incorporate some of the nonchemical
stressors or human activity patterns that might affect nonspatial factors such as mixtures, activities, and
community practices. Mr. Pascual recommended that the group parse the first bullet point and determine
the various issues involved.
Dr. Paloma Beamer, University of Arizona, stated that researchers need better dose estimates and better
methods for interpreting biomonitoring. Researchers must get closer to what they are measuring to access
risk.
Dr. Janis Johnston, AAAS Science and Technology Policy Fellow, noted that researchers need to account
for, quantify, and assess social variables, and these do not easily lend themselves to the process. For
instance, if community members are asked to rank a variable from one to five, this creates noncontinuous
data; however, if asked to rank a variable from one to 100, the task often seems too difficult and
information may be lost. Researchers must decide how to determine which social and contextual variables
are important and apply these to the model.
Mr. Pascual agreed that pertinent social variables must be identified in each case and then converted into
measurable indicators to include in a model. Dr. Bollweg added that researchers must identify and
parameterize variables.
The Office of Research and Development's National Center for Environmental Research 28
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Reif noted that if researchers have, for example, a suite of measured, quantitative airborne exposures
and a suite of questionnaire data, then perhaps a decision tree is a useful approach. This would be an
explicit representation of the interaction between a quantitative variable and a socioeconomic variable.
Dr. Beamer mentioned a paper by Ms. Rhona Julien published in the Journal of Exposure Science and
Environmental Epidemiology, "Pesticide loadings of select organophosphate and pyrethroid pesticides in
urban public housing," in which these types of classification regression trees were used to examine
pesticide levels in Boston public housing.
Ms. Eloise Mulford, EPA, explained that Native American tribes tend to distrust models provided by
EPA. A situation pertinent to tribes is the desire to return to previous diets that consist of more fish. Risk
assessment, however, will examine their current diet, the majority of which might be store-bought
groceries and not fish from a contaminated river. Researchers therefore must determine how to
incorporate the tribes' planned dietary changes into risk assessment models. Another variable has not
been included in previous risk assessments for political reasons; Native American tribe members, unlike
other Americans, cannot relocate to avoid contaminants. This variable increases risk for this population.
Additionally, some tribes have only 100 or 1,000 members, and this is another variable often missed in
risk assessment. Researchers must communicate effectively the risk of 1/1000 to a tribe of only 100
members. Dr. Reif responded that perhaps risk could be presented specifically in terms of the risk per 100
fish from the contaminated river.
Mr. Pascual noted that Ms. Mulford's point was consistent with Dr. Johnston's statement: As researchers
attempt to formalize problem scoping, they must include the typically nonquantifiable values.
Ms. Mulford explained that tribal members tend to be process-oriented. They care about what is included
in the input for risk assessment and also want to know how researchers use the input. Dr. Bollweg
interpreted this as a communication challenge. "Black box" processes are not acceptable to tribes, so
researchers must improve their ability to communicate complex ideas and the extremely mathematically
complicated models behind them.
Mr. Pascual explained that based on the workshop's definition of CBRA, the session participants had
been focusing on chemical and nonchemical stressors but needed to examine the two additional building
blocks, participatory-based research and transparency. Research starts with a holistic perception of the
problems, but analytical modeling tools (such as Analytica and Stella) can identify the primary factors of
interest and allow researchers to choose arrows of association and causation.
Dr. Bollweg stressed that modelers must be able to explain their technically complex models in plain
English. Mr. Pascual suggested that community members be engaged in building the models, using stan-
dard conceptual modeling tools to determine what factors are important. Dr. Beamer added that one of the
goals of modeling is to develop a structure that can be applied from one community to another.
Ms. Mulford added that researchers frequently explain only simple facts to the public, but the knowledge
and understanding of communities should not be underestimated.
Mr. Pascual summarized the important needs that the group had identified:
• Better geospatial characterization of the communities.
• Greater ability to deal with multiple scales (temporal, spatial, or data from multiple sources).
• Greater ability to deal with mixtures versus single insults.
• Better measures of physical variables (e.g., dose).
The Office of Research and Development's National Center for Environmental Research 29
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
• Greater ability to identify which social variables to measure and to turn those variables into
something quantifiable.
• Better measures of quantified social variables.
• Greater ability to explain models and/or to build them in collaboration with the community to ensure
transparency.
Dr. Tilson asked how researchers can validate complex models to ensure they are working. Mr. Pascual
commented that working with communities starting from model conception would be useful because
different people have different versions of reality. If researchers chart out important variables in a group,
they can ascertain that the versions of reality match in a qualitative, consensual manner. Mr. Pascual
added that he prefers using Bayesian mathematical approaches to examine the likelihood of the model
against data that emerge over time. This provides a formal way to test the ability of the model to capture
reality.
Dr. Reif stated that the usual method researchers use to build risk assessment models involves
prespecification. This approach works if the community has identified a problem, but if the problem is not
known, researchers must measure a number of variables and use an empirical model. He wondered if
communities would be amenable to research that determines what is important based on what the
collected data show. The important issues might not be those the community initially thought were
important, so the strength of the model must outweigh prior conceptions about the problem. Mr. Pascual
added that under this premise, when in the laboratory, the goal is to capture all possible data. In the
community setting, however, data are expensive, and this approach may not be possible. Dr. Reif
explained that there would still be an underlying hypothesis that what researchers are measuring is
relevant; determining how factors are important differs from the determination that they are important.
Mr. Pascual added that another significant set of research needs involves verifying and increasing the
credibility of models.
Mr. Schultz noted that when communicating with communities regarding dose, interpretation of what the
dose means in terms of effect is important. Mr. Pascual added that when building exposure models,
researchers must link the dose to both the effect and the source.
Dr. Winona Victery, EPA, mentioned that researchers should consider using data collected by the CDC's
Environmental Public Health Tracking Program, which is attempting to link environmentally measured
situations with health records. Mr. Pascual agreed that pooling data is beneficial when combining data
from multiple sources.
Ms. Segal advised that regarding CBRA and nonchemical stressors, dose-response will shift when other
factors are considered. Different communities will show different dose-responses and effects based on
socioeconomic disparities.
Dr. Beamer noted that exposures cannot occur without activities that lead to them, and there has been
insufficient examination of these activity patterns, such as lead exposure as a result of hand-to-mouth
activity, which might be higher in poorer children with fewer toys.
Mr. Pascual mentioned that a key point regarding national models had been raised at previous sessions.
The basic approach of HB is to say that there is a common model that applies nationwide, but the value of
HB is in viewing the model not as fixed but as stochastic; if data from a certain community are entered,
the value can change. There may be a common model with parameters that vary from location to location.
The Office of Research and Development's National Center for Environmental Research 30
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Researchers then can determine why they vary. HB models are single models working on many scales,
not numerous different models.
Dr. Johnston advised that when researchers display a map, often some Midwestern states have no data
listed, and the people living in those areas will perceive the model as irrelevant. Dr. Roy Whitmore, RTI
International, stated that researchers conducting a community-based study from one of those areas could
still incorporate data from that area into the model but would need less local data if using related data
from other geographic areas. This concept could be explained to the community.
Mr. Schultz asked for clarification on whether Mr. Pascual suggested that researchers use HB methods for
the whole process (from chemical concentration to the health effects) or specifically for estimating
localized concentrations. Mr. Pascual explained that he was working on a project that was attempting to
link societal behaviors and physical changes and determine the valuations, but this was not entirely based
on HB methods. One specific set of issues is related to combining data over several dimensions. He asked
for assistance from the group on accounting for the interactions of multiple stressors.
Dr. Reif noted that when combining multiple data types, decision tree-based models could be effective.
The approach is nonparametric, so these models are not affected by sample size, as are many others. They
also are easy to interpret. Dr. Tilson agreed that this approach is reasonable and asked if research had
been conducted using physiological measures of stress, such as steroid hormones, in subpopulations to
determine if stress is a factor. Dr. Victery noted there was a study that examined cortisol levels and
exposure to violence. Ms. Segal mentioned studies by Dr. Cory-Schlecta evaluating the interaction of lead
and corticosteroids. Dr. Tilson added that many nonchemical stressors will produce a fairly generic stress
response.
Dr. Beamer suggested that researchers incorporate physiologically based pharmacokinetic (PBPK) and
physiologically based pharmacodynamic (PBPD) models into CBRA. For instance, if there is a known
hormone level shown under stress, researchers could incorporate this with another variable with a
physiological basis.
Mr. Pascual added that socioeconomic factors are difficult to desegregate at the individual chemical level
and wondered how researchers could handle this issue. Dr. Reif explained that each individual would
have a decision tree, and if, for example, there were five causes leading to a particular outcome,
community members could be partitioned into five groups. Dr. Pascual stated that the particular behavior
activity could serve as a proxy to estimate exposure to mixtures. Researchers might only be able to study
the effects of mixtures on a cellular mechanistic level. Dr. Beamer explained that this is why more
pharmacodynamics of the PBPD models, as well as data to validate them, are needed. There is a
relationship between physiological and sociological responses, and researchers can use mathematics to
describe physiological factors.
Dr. Tilson noted that regarding the interaction of chemical and nonchemical stressors, if the stress of the
environment produces a response, there will be a differential response to chemical stressors in that
population, which offers some biological plausibility about the interaction. Dr. Beamer added that models
also can incorporate the unique physiologies of different communities.
Mr. Pascual stated that the group had not discussed incorporating community-based information into the
research. Dr. Reif raised the point that when science is presented to the public, what appears to be a
decent weight of evidence to the scientists (such as a 95% confidence interval) is not seen as such by
community members, because the concepts of uncertainty and variability are not widely understood.
Scientists must communicate these concepts so that people understand that the data do apply to them;
how to best accomplish this is unclear.
The Office of Research and Development's National Center for Environmental Research 31
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
Dr. Bollweg responded that people simply want to know if a stressor is safe or not; they do not want to be
given a number. Researchers do not get questions in an objective form, however, and part of the job is to
convert these subjective questions into testable variables.
Dr. Victery noted a use for this concept at the local governmental level. For example, during a
presentation on manganese in the water supply in Wisconsin, there were questions raised on how the
information was ascertained and what indicated that the water was or was not safe. The data should be
user-friendly and easy to locate. Researchers have a great deal of information, but it may not be accessible
to the affected communities.
Ms. Mulford agreed that communities want to know not only whether the water is safe but how scientists
determine this. Dr. Whitmore stated that the answer to whether or not something is safe is not always
"yes" or "no." Mr. Pascual agreed that the binary approach does not always work. Using an analytical
hierarchical process, researchers might not be able to put a number on what people prefer, but they can
decide in an ordinal way what factors are important, weigh different options, and analyze the tradeoff.
Communities need to know that scientists frequently do not deal in certainties. In one study, Mr. Pascual
worked with fishermen in the Philippines, and decision-making was conducted in the form of a board
game. Fishermen learned about the stochasticity of decision-making by playing the game 10 times and
making strategic decisions that led to various outcomes.
Ms. Mulford explained that if agencies list options for tribes in terms of pollution cleanup standards, the
answer they receive may be that none of the options are sufficient, and only zero pollution is acceptable.
A better approach with a community is for the Agency to ask where they should begin to cleanup, and
honor that preference.
Mr. Pascual summarized that the four main areas the group had discussed were: (1) selecting the proper
analytical tools; (2) using these tools to link exposure back to emissions and forward to effects; (3) taking
better measurements on the physical and social sides to feed into the analytical tools; and (4) building up
credibility and learning better ways to verify the models used (i.e., "meta" issues).
Dr. Bollweg pointed out that in terms of modeling exposures to mixtures, there are some new methods,
such as toxicity testing prioritization using high-throughput methods. Researchers can learn which
mixtures (and what concentration of these mixtures) are found repeatedly in large areas. Dr. Reif added
that this is being done for toxic gas, and researchers are attempting to extend the method to other
domains. Dr. Beamer offered that combining PBPK with Bayesian methods might be a way to integrate
some of the issues discussed.
Mr. Pascual suggested that shared, mapable ontologies for organizing data gathered at multiple levels is
critical to ensure that information can be shared and located easily using semantic search engines.
Dr. Reif added that communities should be able to organize data themselves using a desktop tool.
Whoever within a particular community establishes a formal ontology for data sharing can be a contact
person at the community level. Ms. Mulford agreed that a tool that the community can operate themselves
would be beneficial for tribal communities, many of whom do not like to share data. Dr. Whitmore added
that this approach may encourage them to share data, and the National Institutes of Health have developed
some relevant data-sharing protocols.
Mr. Pascual concurred that, for example, if Maricopa County in Arizona can see a benefit from using
New York data, the community may feel a sense of reciprocation. Shared ontologies allow different
versions of reality to be mapped to each other.
The Office of Research and Development's National Center for Environmental Research 32
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
CLOSING SESSION
Breakout Reports to the Group
Breakout Moderators
Drs. Cohen Hubal and Faustman summarized the salient points of Breakout Group #1 (See Appendix A,
Data Needs Outline). The group identified data needs, especially contextual information. Data needs are
driven by community needs. Data access is an issue; existing data may not always be obtainable. A list of
available tools would be beneficial. The differences between vulnerability and susceptibility must be
explained to the community. Development of indicators and metrics is needed as well as translation of
indices to risk. Several options for applying existing tools and developing new tools exist. Detailed case
studies are needed, but completion of demonstration projects could address this. One important point is
that EPA needs to partner with other agencies, universities, NGOs, and advocacy groups. Communication
and the responsibility of a formal report-back to the community are critical, and ethics, training, and
education also need to be considered. Additionally, tools and approaches from other fields also should be
examined and adopted to CBRA as appropriate.
Ms. Knowlton summarized Breakout Group #2's discussion (See Appendix B, The Biological Impact of
Non-Chemical Stressors and Interaction With Other Environmental Exposures Breakout Session
Responses). The group discussed scientific and social data that are not integrated and debated the pros
and cons of local versus national databases. Participants examined the role of communities in improving
data on nonchemical stressors to be used in EPA's traditional risk assessments, including modifying
quantitative data and identifying sources and pathways of exposure, activity patterns, and important social
stressors and health endpoints. Existing CBPR literature, the 2003 EPA Community Involvement
Workshop, and Dr. Barbara Harper's work on Native Americans and treaty rights offer potential models
for involving communities. Existing models from the fields of ecology and the social sciences can be built
on to incorporate the information gained from national databases and local community input into a risk
assessment framework. Participants also suggested that local standards should be developed to accom-
pany national standards, and representatives from the most impacted communities should be present on
national advisory boards. Expanded community involvement may not increase the understanding of inter-
actions between chemical and nonchemical stressors, but it will help make associations that drive
research. In terms of gaps in knowledge and methodology, more community-based studies and laboratory
research are needed to better understand the relationship between environmental and social stress. More
research also is needed to determine the most important nonchemical stressors and identify biomarkers of
stress and its interactions with chemical exposures. The basic assumptions of the source-to-outcome
paradigm must be tested, and researchers must look beyond biological effects and dose-response
relationships to incorporate a more ecologic approach, including risk perception and social/economic
effects.
Dr. Reif and Mr. Pascual provided the summary of Breakout Group #3's session (See Appendix C,
Statistical and Mathematical Modelling). Interpretable solutions exist for answering the question that the
community is asking (i.e., translation of results). Credible results are needed, and explanations that
underestimate the community's ability and desire to understand must be avoided while respecting the
need for nontraditional or advanced methods. Diverse data types, such as environmental, biological, and
social, should be included in statistical modeling. The group discussed how to identify relevant data that
can be converted to an understanding of indicators, which in turn must be associated with chemical
stressors. Data does not need to be stored in one manner as long as it is hierarchical. Analytical issues
include how to manage multiple scales and stressors. A general model can be adapted by geographic
location and include multiple sources. The Hierarchical Bayesian Model requires more research to
increase its ability to add data from multiple sources and scales. One approach to answering the question
of mixtures may be to use desegregation techniques to classify lifestyles that serve as proxies for
The Office of Research and Development's National Center for Environmental Research 33
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
exposures. It is important to ensure that linkages are appropriate in models. A certain level of
transparency is necessary for credibility, and involving the community in building the model will help
accomplish this. The preferred outcomes of stakeholders must be identified, and the most important
mixtures must be identified and prioritized.
Closing Remarks
Michael Callahan, U.S. EPA
Mr. Callahan commented that he is encouraged that a workshop such as this was organized and noted the
quality of the presentations. He provided a brief history of cumulative risk assessment, stating that the
first cancer risk report in 1976 has become simplified over the years, and too much emphasis has been
placed on some assumptions. Many documents and reports during the subsequent 30 years have provided
a revisiting of these assumptions. The Cumulative Risk Technical Panel has commissioned a series of
papers regarding issues, case studies, and research needs in cumulative risk assessment. CBRA should be
considered a wise investment because communities have begun to request it, EPA's relevance with the
public is at stake, and issues of fairness are involved. Environmental justice groups have determined that
CBRA is a good tool for communities. Communities are not asking for total risk, and some parts of the
assessments the communities desire can be accomplished now.
Some communities perceive that risk assessment does not work for them as a result of items such as
cascading effects, nonconventional stressors, and potential losses being omitted from past risk
assessments. Physical and spiritual losses that may not be identified in a traditional risk assessment but
are important are loss of land, language, spirituality, extended family relationships, sense of belonging,
autonomy, rights, self-sufficiency, social structure, connection to land, culture and tradition, identity,
history, cultural pride, community, and trust. EPA managers are concerned that including these items
contributes to "mission creep," but even under the narrowest view of EPA's mission (i.e., identifying
harm as a result of chemical exposures) these factors constitute harm. Public needs are a part of EPA's
priority, and EPA needs to respond to the public's question in such a manner that demonstrates
understanding and the desire to help.
Vulnerability is the state of being open to harm as a result of the inability to cope with a hazard because
of biological susceptibility, prior exposure or disease state, or lack of the resources for resilience.
Vulnerability can mean that the exact same exposure can result in widely different effects; equal exposure
is not equitable. Three levels of coping exist: (1) nonerosive, (2) erosive, and (3) failed. Risk assessors
consider the first two stages but rarely consider the third. This third stage needs to be considered, and
communities have known that for quite some time. The third stage provides some range of vulnerability.
CBRA can begin with screening methods that determine important nonchemical stressors and factors that
contribute to vulnerability. CBRA is not an all-or-nothing process; it starts step by step. Investment in
CBRA is important because demands for it will increase, it will enhance the Agency's relevance and
credibility, and it can be entered into in a modest, step-wise manner.
Discussion
Dr. deFur asked what the next step was to continue this discussion on a larger scale and to increase
participation by individuals from other parts and outside of the Agency. Mr. Callahan replied that a
bottom-up approach was the key; other groups will follow as more dialogues occur.
A participant commented that CBRA is necessary, but quantification is extremely difficult. He asked if
quantification is necessary to mitigate risk. Mr. Callahan responded that it is not.
The Office of Research and Development's National Center for Environmental Research 34
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
A participant stated that tribes deal with stress in different manners to mitigate final risk. Mr. Callahan
agreed that tribal examples are unique, and decision-makers must be aware of the unique harms facing
tribes. A participant agreed that community values must be included and prioritized. Mr. Callahan
answered that this is what comparative risk assessment is (i.e., how risk is ranked according to values).
A participant suggested that communication within EPA be improved, because frequently after the
condition of the environment has been determined, the environment has changed.
A participant agreed with the concept of placing stresses in an economic context because communities
need to know the economic consequences of risk. Mr. Callahan noted that poverty is a correlate and may
be one way to quantify various issues.
Ms. Segal thanked the presenters for their excellent presentations, which received many favorable
comments from attendees. She thanked Dr. Cohen Hubal, Ms. Knowlton, and Dr. Reif for organizing the
breakout sessions and Mr. Pascual, Mr. Bangs, Dr. Meta Bonner, Mr. Schultz, and Mr. Lakin for their
assistance in organizing the workshop. She recognized Mr. Fields as the impetus for the workshop, and
thanked him for his guidance. He and Ms. Deener contributed to the original proposal for the workshop.
Dr. Cohen Hubal thanked Ms. Segal for her organization of the workshop.
The meeting was adjourned at 1:05 p.m.
The Office of Research and Development's National Center for Environmental Research 35
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
APPENDIX A: DATA NEEDS OUTLINE
1. Data needs—contextual information
a. Based on scoping
b. Community-level concerns
c. Contextual experts needed
d. Community-driven versus community-based
2. Data access
a. Guidance on available sources
b. Multi-agency
c. Surveillance (e.g., CDC, multi-university, environmental health tracking)
d. Indicators
e. EPA/National Institute of Environmental Health Sciences Children's Centers
f Databases that are available and accessible
g. GAPS AT THE LOCAL LEVEL—AND ACCESS (e.g., NHANES)
3. Definition of community
a. What important factors characterize similarities/differences among communities (when is
extrapolation appropriate)?
b. What factors are important for characterizing vulnerabilities that may interact to increase risk
from chemical exposure?
c. Geography is not always a defining factor (Not all communities geographically bound, may have
shared exposures, vulnerability factors)
4. Development of indicators and metrics
a. How much data are needed, when do you have enough, when does too much limit interpretation?
5. Translation from indices to risk
a. What available social indices may be applicable for EPA cumulative risk assessment?
b. How can these indices be translated in a quantitative way to assess risk?
c. Importance of both qualitative and quantitative indices
6. Application of existing tools and developing new tools
a. Geographic information systems have tremendous power but significant limitations in
interpretation (often because of data limitations)
b. Linking with risk
c. Make tools available and accessible to community (Google Earth-ish)
7. Multidisciplinary teams
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
8. Case studies
a. Review, compile
b. Lessons learned
c. Use available tools
9. Demonstration projects
a. Exposure-based (highly exposed)
b. Outcome-based (specific health issues)
c. Population-based (particularly vulnerable group)
d. Solutions-based (identification of positive trend, understand why)
10. EPA needs to partner!! (Responsibility)
a. National Institutes of Health
b. CDC/Agency for Toxic Substances and Disease Registry
c. Department of Housing and Urban Development
d. Departments of Transportation, Agriculture, Education, etc.
e. State and local level
11. Partner for context
a. Universities
b. Non-governmental Organizations
c. Advocacy groups
12. Communication
a. Scoping
b. Interpretation
c. Methods of dialogue and interaction
13. Ethics
a. Balance accessibility with confidentiality
b. Research needed on de-identifying data to improve access for analysis
c. Data ownership
d. Report back
e. Honor and build off of existing relationships in community!
14. Training/education
a. Attract more representatives of minority communities to field
b. Education in academia on how to work with communities and conduct CBPR
c. Communities need introduction to RA—basic training on environmental health and RA
15. Mining other fields
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
APPENDIX B: THE BIOLOGICAL IMPACT OF NON-CHEMICAL STRESSORS AND INTERACTION
WITH OTHER ENVIRONMENTAL EXPOSURES BREAKOUT SESSION RESPONSES
The following was recorded from the session flipchart.
1. Identify tools and approaches that may be applied to conduct CBRA. (Workshopparticipants: We will
touch on this question briefly during the breakout session, but if you know of additional research
programs or studies that contribute to the body of knowledge, please e-mail them to the facilitator at
knowlton.carrie@epa.gov before or after the workshop.}
• What data are available on biological impact of nonchemical stressors and the associated
interaction with environmental exposures?
• Census data
• Interagency Forum on Aging-Related Statistics
• Extensive social/economic data, just not commonly used by EPA
• Must make a distinction between local data and national databases
• Stress and caregiver studies give insight into biological effects of stress
• What models exist to help us understand interactions of nonchemical stressors and environmental
exposures?
• THRIVE social capital index
• Social coping models
• High-performance computing
• Epigenetics
• What techniques (i.e., measurement, modeling) can be borrowed from other disciplines to
quantify the effects of nonchemical stressors?
• Computer simulations
• Methods from social epidemiology
• Behavioral sciences
• Ecology (community structure, disturbance)
2. Discuss how to incorporate community-based information into traditional EPA risk assessments.
• How can community-based participatory research frameworks be most useful for identifying
important exposures and risks?
• Modifiers of quantitative data
• Sources and pathways of exposure
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
• Lifestyle/activity pattern
• Social stressors/poverty
• Must demonstrate CBRA to be an improvement on traditional risk assessment
• Increased participation -^ more data
• What methods have been successfully used to collect community-based information regarding
nonchemical health issues? Are these methods transferable to any community?
• Review existing literature and outcome of EPA's community involvement conference
• Neurotoxicology has published an article on a Web-based community risk assessment tool
• Barbara Harper's work on Native Americans and treaty rights
• Use of advisory boards representative of communities
• Create models based on lessons learned
• Real-time surveys (e.g., sensor technology) can lead to increased participation
• Need a fundamental change in the risk assessment process
• Need to look at biological endpoints, not single chemicals
• How can community knowledge be incorporated into EPA's risk management process?
• Can lead to standards based on local conditions, as opposed to national standards
• Lead to community-driven programs, designed by and implemented by communities
• Local media can become involved to disseminate information
• National risk management and standard setting can incorporate community advisory board
with representatives from most impacted communities
• What is the role of community knowledge in understanding the interaction of multiple stressors?
• Community knowledge may not help us understand interactions but will help make
associations that drive research
3. Evaluate the research needs for CBRA.
• What are the most significant gaps in our understanding of the biological impacts of stress and
interactions with environmental exposures?
• Need research on effects of combination of stress and chemical exposure
• What makes certain communities more vulnerable?
• Community epidemiological studies need to be combined with animal data and laboratory
research
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
• Biomarkers
• Need to look beyond biological effects at risk perception and social/economic effects
• Need to know which nonchemical stressors are most important
What are the important methodological gaps for incorporating nonchemical stressors into
traditional EPA risk assessments? How can this information be used in risk assessments?
• Need to test basic assumptions of source-to-outcome paradigm
• Need an ecologic approach beyond dose-response
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
APPENDIX C: STATISTICAL AND MATHEMATICAL MODELLING
• Interpretable solutions
• Answer the question the community is asking (translate results)
• Credible results
• Avoid the "black-box" explanation, but respect the need for nontraditional or advanced methods
• Include diverse data types (environmental, biological, social . . .)
• Data sharing (ontologies)
• Can analysis be a two-way street?
The Office of Research and Development's National Center for Environmental Research
-------
U.S. EPA Workshop on Research Needs for Community-Based Risk Assessment
ADDENDUM: BREAKOUT SESSION PARTICIPANTS
Breakout Session I
Name
Affiliation
Eggers, Mari
Faustman, Elaine
Ferguson, Alesia
Hu, Chih-yang
Cohen Hubal, Elaine
Kizakevich, Paul
Lakin, Matthew
Lobdell, Danelle
Rao, Pamela
Schlenker, Thomas
Schreinemachers, Dina
Thomas, Kent
Watkins, Timothy
Wilson, Sacoby
Breakout Session II
Name
Montana State University at Bozeman
University of Washington
University of Arkansas for Medical Sciences
Louisiana State University
U.S. EPA
RTI International
U.S. EPA
U.S. EPA
Farmworker Justice
Public Health Madison-Dane County
U.S. EPA
U.S. EPA
U.S. EPA
University of South Carolina
Affiliation
Bangs, Gary
Callahan, Michael
Deener, Kacee
deFur, Peter
Fields, Nigel
Highsmith, Ross
Hubal, Rob
Knowlton, Carrie
Lowe Liang, Debbie
MacPhail, Robert
Rao, Ravishankar
Rouse, Tonesia
Sanchez, Yolanda
Sykes, Kathy
Weiss, Bernard
Wells, Sharon
Wright, Michael
Session III
Name
U.S. EPA
U.S. EPA
U.S. EPA
Virginia Commonwealth University
U.S. EPA
U.S. EPA
RTI International
ASPH Fellow, U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
ASPH Fellow, U.S. EPA
U.S. EPA
University of Rochester
U.S. EPA
U.S. EPA
Affiliation
Beamer, Paloma
Bollweg, George
Johnston, Janis
Mulford, Eloise
Pascual, Pasky
Reif, David
Schultz, Brad
Segal, Deborah
Tilson, Hugh
Victery, Winona
Whitmore, Roy
University of Arizona
U.S. EPA
AAAS Science and Technology Fellow, U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
U.S. EPA
RTI International
The Office of Research and Development's National Center for Environmental Research
------- |