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

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U.S. EPA Workshop on Research Needs for Community-Based
                   Risk Assessment

                  October 18-19, 2007
               Research Triangle Park, NC

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              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

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Session I: Data Needs and Measurement
    Methods for Community-Based
          Risk Assessment

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               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

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               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

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               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

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Session II: The Biological Impact of Non-
Chemical Stressors and Interaction With
    Other Environmental Exposures

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               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

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               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

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Session III: Statistical and Mathematical
 Modeling for Community-Based Risk
            Assessment

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               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

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               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

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               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

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Appendices

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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

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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

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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

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     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

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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

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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.

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                                                                                 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

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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

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      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
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              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.
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              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.


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              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


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               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.
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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


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              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
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              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


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              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.
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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.
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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
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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.
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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-


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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


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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.
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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.


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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.
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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


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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.
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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.
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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

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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.


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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.
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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.


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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
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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.
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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
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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.
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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.
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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).
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•   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.
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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.
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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.
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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
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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.
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              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.
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              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
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              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
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              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

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              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

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       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
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              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?
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              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
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