EPA/600/R-00/049

STRATEGIC PLAN FOR THE ANALYSIS OF THE

NATIONAL HUMAN EXPOSURE ASSESSMENT

SURVEY (NHEXAS) PILOT STUDY DATA

National Exposure Research Laboratory 

and

National Center for Environmental Assessment

Office of Research and Development

U.S. Environmental Protection Agency

November, 2000
ii

Disclaimer

This document has been reviewed in accordance with U.S. Environmental Protection Agency

policy and approved for publication. Mention of trade names or commercial products does not

constitute endorsement or recommendation for use.
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Table of Contents

Page

List of Tables .................................................................. v

Authors and Contributors ........................................................ vi

Acknowledgments ............................................................. vii

EXECUTIVE SUMMARY ....................................................... 1

1. INTRODUCTION ........................................................... 3

2. OVERVIEW OF NHEXAS .................................................... 5

2.1 BACKGROUND ON EXPOSURE TO CHEMICAL POLLUTANTS .............. 5

2.2 THE PURPOSE OF NHEXAS ............................................ 6

2.3 HISTORY AND PARTICIPATING ORGANIZATIONS ........................ 7

2.4 MAJOR DESIGN ELEMENTS ............................................ 8

3. STRATEGIC FRAMEWORK ................................................. 10

4. TOPIC AREAS AND PROJECTS ............................................. 17

4.1 DATA ANALYSIS AREA ONE: DESCRIPTIVE STATISTICS ................. 18

4.1.1 Overview ...................................................... 18

4.1.2 Developing Priorities for the Projects .................................. 19

4.2 DATA ANALYSIS AREA TWO: PREDICTORS OF EXPOSURE AND DOSE .... 23

4.2.1 Overview ...................................................... 23

4.2.2 Developing Priorities for the Projects .................................. 24

4.3 DATA ANALYSIS AREA THREE: SPATIAL AND TEMPORAL 

VARIABILITY ....................................................... 30

4.3.1 Overview ...................................................... 30

4.3.2 Developing Priorities for the Projects .................................. 31

4.4 DATA ANALYSIS AREA FOUR: AGGREGATE EXPOSURE, PATHWAY

ANALYSIS, AND CUMULATIVE RISK ................................... 37

4.4.1 Overview ...................................................... 37

4.4.2 Developing Priorities for the Projects .................................. 37

4.5 DATA ANALYSIS AREA FIVE: EVALUATION/REFINEMENT OF 

CURRENT EXPOSURE MODELS AND ASSESSMENTS ..................... 42

4.5.1 Overview ...................................................... 42

4.5.2 Developing Priorities for the Projects ................................. 43

4.6 DATA ANALYSIS AREA SIX: DESIGNING EXPOSURE STUDIES ............ 49

4.6.1 Overview ...................................................... 49

4.6.2 Developing Priorities for the Projects ................................. 50
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APPENDIX A: List of Workshop Participants ...................................... A-1

APPENDIX B: Science Advisory Board Reviewers .................................. B-1

Table of Contents

(cont’d)

Page

APPENDIX C: NHEXAS Projects and Analyses—Completed and In Progress ............ C-1

APPENDIX D: Project Priority Listings ........................................... D-1

APPENDIX E: Project Descriptions .............................................. E-1
v

List of Tables

Number Page

1 Summary of NHEXAS Studies ................................................. 9

2 Key SAB/IHEC Recommendations for the Analysis of NHEXAS Pilot 

Study Data ............................................................... 13

3 Relationship of NHEXAS Pilot Study Data to Advancing EPA Strategic Goals 

Identified in the Government Performance and Results Act (GPRA) ..................... 14

4 Key NHEXAS Objectives ................................................... 16

5 Descriptive Statistics Projects and Priorities ...................................... 20

6 Predictors of Exposure and Dose Projects and Priorities ............................. 25

7 Spatial and Temporal Variability ............................................... 32

8 Aggregate Exposure, Pathway Analysis, and Cumulative Risk ......................... 38

9 Evaluation/Refinement of Current Exposure Models and Assessments ................... 43

10 Designing Exposure Studies .................................................. 51
vi

Authors and Contributors

Primary Authors

Maurice Berry, National Exposure Research Laboratory (NERL)

Judith A. Graham, NERL

Karen Hammerstrom, National Center for Environmental Assessment (NCEA)

Stephen Hern, NERL

Haluk Ozkaynak, NERL

Dale Pahl, NERL 

James Quackenboss, NERL

Major Contributors

Kelly Leovic, NERL

Gary Robertson, NERL

Linda Sheldon, NERL

William Steen, NERL
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Acknowledgments

The authors are grateful to the participants in the NHEXAS Workshop, which was held in

Research Triangle Park, NC, from July 27 to 30, 1999. The individuals identified in Appendix A

provided expert advice to identify scientific approaches for analyzing the data from the NHEXAS pilot

studies.

The authors are also grateful to the Integrated Human Exposure Committee (Appendix B) of the

U.S. Environmental Protection Agency’s Science Advisory Board for their insightful review of the draft

of this strategy on July 10-11, 2000.

The authors are also grateful to John Barton, David Belton, Yvonne Harrison, Bettye Kirkland,

and Carolyn Perry of OAO Corporation for their parts in the production of this publication.

Contact: Sheldon.Linda@epa.gov

Additional copies available after December 20, 2000 on www.epa/nerl/nhexas/htm
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EXECUTIVE SUMMARY

The Office of Research and Development (ORD) of the U.S. Environmental Protection Agency

(EPA) initiated the National Human Exposure Assessment Survey (NHEXAS) in the early 1990's. It

was a population-based pilot study of the exposure of over 500 people in three areas of the U.S. to

metals, pesticides, volatile organic compounds, and other toxic chemicals. Measurements were made

of the air people breathed, the foods and beverages they consumed, and the soil and dust in/near their

home. Chemicals in their blood and urine were measured. The participants also completed

questionnaires to help identify possible sources of exposures and to characterize activities that might

contribute to exposure. To this date, NHEXAS remains the largest multimedia, multipathway,

multichemical study of its kind. Key goals included evaluating the feasibility of conducting such a large

study, documenting the population distribution of exposure to the chemicals examined, understanding

the factors that contribute to high exposures, and improving the accuracy of exposure models.

Such a study produces a multitude of data that must be thoughtfully analyzed to realize its full

potential. EPA’s Science Advisory Board (SAB) recommended that EPA develop a strategy to

analyze the data to ensure the optimal use of the data (EPA-SAB-IHEC-ADV-99-004,

www.epa.gov/sab). Therefore, ORD developed this Strategic Plan. ORD began with a workshop at

which about 70 scientific and policy experts from ORD, EPA program offices, EPA regions, other

federal agencies, state health agencies, academia, and private institutions offered their suggestions on

the most useful analyses of the NHEXAS pilot data. ORD used their thoughtful contributions as the

basis to begin development of the Strategic Plan. The draft Plan was reviewed by the SAB (EPASAB-IHEC-00-018, www.epa.gov/sab), and made available to all EPA program offices and the

public. This document has been revised based upon those recommendations.

The Strategic Plan describes projects in six topic areas: descriptive statistics; predictors of

exposure and dose; spatial and temporal variability; aggregate exposure, pathway analysis, and

cumulative risk; evaluation/refinement of current exposure models and assessments; and designing

exposure studies. Criteria, founded on both the near- and long-term value to EPA, were established

for ranking projects within each of these topic areas. The text describes how the criteria were applied

to each project. The projects are described in the appendix. This prioritization will be used as a guide
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for ORD to implement the analyses. To expand the opportunities for all interested persons to get

involved, the NHEXAS information is being prepared for entry into a publically available database, with

appropriate metadata, in late 2001.
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1. INTRODUCTION

To evaluate the risks posed by chemical pollutants in the environment, the U.S. Environmental

Protection Agency (EPA) must be able to estimate the number of people exposed to the pollutants, as

well as the magnitude and duration of the exposure. Typically estimates of exposure have been based

on “default assumptions” such as emissions or environmental concentration data, rather than actual

measures of human exposure to contaminants. Without measurements of human exposure, these

default assumptions are of limited value because they do not reflect actual patterns (distributions) of

human exposure to chemicals in the environment.

Increasingly, EPA’s scientific advisors are concerned about reliance on these default

assumptions—particularly when evaluating the risks from exposure to environmental contaminants or

when estimating the benefits that may be obtained from managing these risks. Addressing these

concerns is a vital link in reducing the scientific uncertainty in health risk assessment and in regulatory

decision making.

To respond to these concerns, EPA’s Office of Research and Development (ORD) sponsored

three related pilot studies known as the National Human Exposure Assessment Survey (NHEXAS). 

The NHEXAS studies tested protocols for acquiring population distributions of exposure measurements

and developed exposure databases for use in exposure models and assessments and, hence, risk

assessments. The principal objectives of the NHEXAS pilot studies were to (1) evaluate the feasibility

of NHEXAS concepts, methods, and approaches for the conduct of future population-based exposure

studies; (2) evaluate the utility of NHEXAS data for improved risk assessment and management

decisions; (3) test the hypothesis that the distributions of exposure given by modeling and extant data do

not differ from the measurement-based distributions of exposure; (4) define the distribution of

multipathway human exposures for a relatively large geographic area; and (5) stimulate exposure

research and forge strong working relationships between government and nongovernment scientists.

During 1998, the Science Advisory Board’s (SAB’s) Integrated Human Exposure Committee

(IHEC) conducted a review of the NHEXAS pilot studies. The SAB issued a report of their review

early in 1999 (Appendix B). This report—An SAB Advisory: The National Human Exposure

Assessment Survey (NHEXAS) Pilot Studies (EPA-SAB-IHEC-ADV-99-004, February
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1999)—praised the NHEXAS pilot studies and recommended several actions to ensure that as much

benefit as possible is derived from this very rich database. One major recommendation was to develop

a strategic plan for completing the analysis of the NHEXAS pilot data.

This report represents the strategic plan requested by the SAB. To develop background

information for this strategic plan, ORD convened a workshop from July 26 through 28, 1999, to

obtain a wide range of expert opinion on which scientific analyses would be helpful to interpret the

NHEXAS data. The scientific analyses identified during the workshop are documented in a report

entitled Proceedings of the NHEXAS Data Analysis Workshop (EPA 600/R-99/077; October

1999). An electronic version of the proceedings document is available on the Internet at

www.epa.gov/nerl/nhexas. The proceedings document represents one significant source of information

considered by the authors of the ORD strategy for the analyses of the NHEXAS pilot study data. A

draft was reviewed by the IHEC in July, 2000. Copies were sent to the EPA Program Offices and

made available to the public. The IHEC recommendations served as the basis for revising the Strategy

(An SAB report: the draft strategic plan for the analysis of national human exposure assessment

survey (NHEXAS) pilot study data (EPA-SAB-IHEC-00-018, September 2000,

www.epa.gov/sab)).

Two projects discussed during the NHEXAS Data Analysis Workshop are not included in this

strategy: a project to develop and review a publicly accessible NHEXAS database and a project to

document the lessons learned from the field recruitment and sampling portions of the pilot studies. 

ORD initiated work on these projects during FY99 because they represent essential precursors to the

data analysis projects discussed in this plan. For example, many NHEXAS data analyses described in

this report cannot proceed until ORD completes a publicly accessible database. These projects are

described in more detail in Appendix C.

This report incorporates both strategic objectives and a description of projects arising from those

objectives. On one hand, it has more structure than a typical strategy because of the need for a

framework for classifying and describing a large number of highly related analyses. On the other hand,

it avoids the prescriptive approach of a detailed workplan to permit researchers to engage their

creativity and expertise in defining the details. Although this approach represents more narrative than

that found in some strategies, it represents a necessary elaboration on the extensive information
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presented in the two documents cited above. Therefore, most projects are relatively broad in scope

and large in size.

Section 2 of this strategic plan contains an overview of the NHEXAS pilot studies to provide the

background on the broad types of data available. Section 3 describes the strategic framework that

ORD developed to prioritize and recommend analyses of the NHEXAS pilot study data. Section 4

summarizes the analysis projects and presents the priorities for implementing them. Appendix A lists

the participants in the July 1999 NHEXAS Data Analysis Workshop. Appendix B lists the IHEC

participants in the July 2000 SAB review. Appendix C describes the ongoing analyses, including the

development of the database and the scope of the lessons-learned project, and lists the titles of

NHEXAS papers that have been published or are in preparation at this time. Appendix D is a listing of

the priorities for all of the projects. Appendix E contains the description of the projects referred to in

the main text.

It is clear that many organizations and individuals are interested in the NHEXAS databases, in

learning about the major findings of the NHEXAS pilot studies, or in performing their own analyses of

the data. ORD plans to respond to this interest by establishing a web site to communicate about the

NHEXAS analyses and to ensure ease of access to the NHEXAS data.

2. OVERVIEW OF NHEXAS

2.1 BACKGROUND ON EXPOSURE TO CHEMICAL POLLUTANTS

To assess the risks posed by chemical pollutants in the environment, EPA must be able to

estimate the number of people exposed to these chemicals and the intensity of exposure. In the past,

most studies have focused on exposure to one chemical at a time by one route of exposure. For

instance, a study might look at how much of a particular chemical is found in outdoor air. In many

cases, these studies have relied on very indirect measures to estimate exposure to the chemicals. An

example would be to sample emissions from a smokestack and then apply air transport models to

predict exposure to residents in the surrounding area.
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Although such studies are important, studying chemicals and sources in isolation does not reflect

actual patterns (distributions) of human exposure to chemicals in the environment. In reality, people can

be exposed to chemicals from a variety of sources that contaminate water, food, air, dust, and other

media. Exposure to a single chemical may occur from contact with several environmental media (e.g.,

air, water), via several pathways (e.g., hand-to-mouth transfers, food), and through several routes (i.e.,

inhalation, oral, dermal). Additional complexities arise when considering an individual’s exposure to

multiple chemicals at any point in time or over extended periods. The fact that different people also

spend varying amounts of time indoors and outdoors or otherwise engage in activities that can have

important impacts on chemical exposure adds to this complexity. More accurate assessments of risks,

therefore, must take into account exposure to multiple chemicals from various routes and media. By

understanding total or aggregate exposure, it also will be possible to identify those pathways and routes

responsible for the greatest exposure, thereby providing direction for decisions on the most effective

strategies to reduce risks.

2.2 THE PURPOSE OF NHEXAS

NHEXAS, in its fullest sense, is a conceptual design, which, on implementation, will have longterm implications to exposure research and assessment. The ultimate goal is to document status and

trends of national distributions of human exposure to potentially high-risk chemicals to improve the

accuracy of exposure (and risk) assessments and to evaluate whether exposure (and risk) is

deteriorating or improving over time with the application of risk management steps. However, such an

extensive program requires much preparation, including making improvements in the state of exposure

science. The Phase I pilot projects are the initial phase of this long-term program. Based on the

scientific advances from this first phase of NHEXAS, two follow-up phases are envisioned. One

encompasses special studies to test particular hypotheses related to issues, such as characterization of a

pathway of concern for a specific subpopulation or a chemical of concern at specific geographic scales

(community and regional) or an uncertainty related to the effect of temporal variability in an exposure

assessment model. The second is the design and implementation of a much broader national survey of

population-based exposures, building on the foundation laid by the pilot-phase investigations.
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Phase I of NHEXAS (hereafter referred to as just NHEXAS or pilot NHEXAS studies) is

perhaps the most ambitious study ever undertaken to evaluate total human exposure to multiple

chemicals on both community and regional scales. It focuses on the exposure of people during their

daily lives to environmental pollutants. To accomplish this, hundreds of volunteer participants were

selected randomly from several areas of the country to obtain a population-based probability sample. 

NHEXAS scientists measured the levels of a suite of chemicals to which participants were exposed in

the air they breathe, in the foods and beverages they consume, in the water they drink, and in the soil

and dust around their homes. Measurements also were made of chemicals or their metabolites in

biological samples (including blood and urine) provided by the participants. Finally, participants

completed questionnaires to help identify possible sources of exposure to chemicals and to characterize

major activity patterns and conditions of the home environment.

In addition to improving measurement-based estimates of total exposure to chemicals and

contaminants, NHEXAS has the following aims.

• Identify subgroups of the general population that are likely to be highly exposed (at least the 75th

percentile) to chemicals in their environment.

• Provide a baseline of the normal range of exposure to chemicals in the general population that can be

used to compare to the results of other investigations conducted at particular sites of concern or to

address specific routes.

• Compare the results of a 1-week “snapshot” of exposure to the results obtained from multiple

sampling cycles over a year.

• Evaluate and improve the accuracy of models developed to predict or diagnose exposure of people

to chemicals.

• Test and evaluate different techniques and design approaches for performing multimedia,

multipathway human exposure studies.

2.3 HISTORY AND PARTICIPATING ORGANIZATIONS

NHEXAS has been implemented with extensive research collaboration that includes scientists

from EPA’s ORD, from other federal agencies, and from leading academic and research institutions. 
8

Scientists from the Food and Drug Administration (FDA) and from the Centers for Disease Control

and Prevention (CDC) participated through interagency agreements with EPA scientists in the analysis

of samples. Scientists from the National Institute for Standards and Technology provided quality

assurance (QA) support through an interagency agreement with EPA. The NHEXAS projects were

funded as cooperative assistance agreements and coordinated by EPA’s ORD. These cooperative

agreements were awarded after a national research solicitation and peer review by national scientific

experts.

(1) The cooperative agreement supporting the Arizona study included the University of Arizona,

Battelle Memorial Institute, and the Illinois Institute of Technology.

(2) The cooperative agreement supporting the Region V study (states of Illinois, Indiana,

Michigan, Minnesota, Ohio, and Wisconsin) included the Research Triangle Institute and the

Environmental Occupational Health Sciences Institute (EOHSI). A related smaller-scale study

in Region V focused on children’s exposures to pesticides and was conducted with the

participation of the Minnesota Department of Health. 

(3) The cooperative agreement supporting the Maryland study included Harvard University,

Emory University, Johns Hopkins University, the Southwest Research Institute, and Westat,

Inc.

2.4 MAJOR DESIGN ELEMENTS

Table 1 summarizes the major design elements of NHEXAS. There were common features

across the three consortia. All three consortia used the same basic set of questionnaires. Within

chemical classes selected by the consortia, each consortium analyzed for a basic set of chemicals

(primary analytes). However, by utilizing three consortia, alternative and innovative variations on the

theme of multimedia measurements to estimate total human exposure were possible. For example, each

consortium was able to target some specific concerns or opportunities. Two of the consortia focused

on measuring potential exposures of each participant once; one consortia studied fewer people but

repeated the measurements several times over the year to enable estimates of temporal variability for

the exposures and activities of interest.
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The participants were selected through a probability sample to permit subsequent statistical

inferences about the larger population. The only exception was a special panel on children exposed to

pesticides. This was based on oversampling households reporting more frequent applications of

insecticides and on a commercial listing of households with listed telephone numbers that were

predicted to have age-eligible children.
TABLE 1. SUMMARY OF NHEXAS STUDIES

Consortium

University of Arizona/Battelle Memorial

Institute/Illinois Institute of Technology

Research Triangle Institute/Environmental and

Occupational Health Sciences Institute

Harvard/Emory/Johns Hopkins/

Southwest Research Institute/Westat

Type of Study Exposure field study Exposure field study Special study: relation of short-term

data to longer term exposures

Geographic

 Region

Arizona Region V (Illinois, Ohio, Indiana, Michigan,

Minnesota, and Wisconsin)

Baltimore and surrounding counties

Design Representative sample of general population Representative sample of general population Representative sample includes

suburban, urban, and rural groups

Approximate

Number of People

179 (plus others in sampled households) 249, plus 52 for pesticides (no others in sampled

households)

53 people sampled six times over

1 year

Analytes Pb, As, Cd, Cr, Ni, Ba, Mn, Se, V, Cu, and Zn;

benzene, chloroform, perchloroethylene,

trichloroethylene, methylchloroform, styrene,

toluene, xylene, p-dichlorobenzene,

formaldehyde, 1,3,-butadiene, methylene

chloride, carbon tetrachloride, plus 11 additional

VOCs; chlorpyrifos, diazinon, malathion, and

carbaryl 

Pb, As, Cd, Cr; benzene, chloroform,

perchloroethylene, trichloroethylene,

methylchloroform, styrene, toluene, xylene, and

p-dichlorobenzene; chlorpyrifos, diazinon,

malathion, atrazine, chlordane, dieldrin,

heptachlor, 4,4'-DDE, -DDD, and -DDT;

B(a)P, anthracene, phenanthrene, pyrene,

B(a)A, acenaphthylene, fluoranthene,

B(g,h,i)perylene, and indeno(1,2,3-c,d)pyrene

Children’s study (pesticides and PAHs) 

Pb, As, Cd, and Cr; chlorpyrifos,

diazinon, malathion, atrazine (water

only), chlordane, dieldrin, heptachlor,

4,4'-DDE, -DDD, and -DDT; B(a)P,

anthracene, phenanthracene, and

chrysene

Samples Air, water, food, and beverages; soil/dust and

surfaces; urine and blood

Air, water, food, and beverages; soil/dust and

surfaces; urine and blood

Air, water, food, and beverages;

soil/dust and surfaces; dermal; urine

and blood

Questionnaire NHEXAS NHEXAS NHEXAS

9
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Chemicals to be analyzed by NHEXAS were chosen because they are known (or strongly

suspected) to present major environmental health risks, had been found in two or more environmental

media (air, water, soil, or food), and had been identified as being of importance to several EPA

program or regional offices or to other federal agencies. Chemicals were selected only if it was feasible

to collect and analyze them. The chemicals fall into three categories: (1) volatile organic compounds

(VOCs), such as trichloroethylene, benzene, and perchloroethylene; (2) metals, such as lead, arsenic,

and cadmium.; and (3) pesticides, such as the herbicide atrazine and the insecticides, chlorpyrifos,

diazinon, and malathion. In some media, measurements of selected polycyclic aromatic hydrocarbons

(PAHs) were made.

3. STRATEGIC FRAMEWORK

This Section describes the strategic framework that ORD developed to identify, characterize, and

prioritize important analyses of the NHEXAS pilot study data. The starting point for developing the

strategic framework was the NHEXAS Data Analysis Workshop that ORD convened in July 1999. 

About 160 scientists and science policy experts were invited to the workshop; Appendix A identifies

those who were able to attend. Each participant received a copy of the SAB advisory report and

extensive background information on NHEXAS well in advance of the workshop itself. Workshop

participants identified and described a number of analysis projects for interpreting the NHEXAS pilot

study data. These projects are documented in the Proceedings of the NHEXAS Data Analysis

Workshop (EPA 600/R-99/077).

After the workshop, each analysis project was reviewed and projects with a substantial amount

of overlap or duplication were merged. The large number of very worthwhile analysis projects created

a significant challenge for ORD: that of establishing priorities to ensure that the “critical” projects are

funded as quickly as possible. Many criteria were considered for sorting these projects and

establishing priorities (e.g., relevance to Agency GPRA Goals, relevance to previous SAB

recommendations, relevance to regulatory needs or timeframes, degree of scientific uncertainty in a
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given component of exposure assessment, feasibility). Ultimately, the strategic framework adopted

consists of two logical steps.

A. In the first step, analysis projects were classified according to the type of scientific

interpretation contemplated. This classification resulted in six distinct topic areas:

1. Descriptive Statistics These projects describe the basic features of the

NHEXAS study results, both for the measurements and the questionnaires, and

provide comparisons between demographic groups. 

2. Predictors of Exposure These projects address the relationships among

various type of measurements (environmental, exposure, and biomarkers),

questionnaires, and activity diaries with a view towards whether one type of

measurement, possibly in combination with questionnaire/activity information,

can be an indicator of another type of measurement.

3. Spatial and Temporal Variability These projects involve analyzing the

variability in human exposures to both single and multiple chemicals, as well as

the key factors that affect inter- and intra-individual variability in exposures.

4. Aggregate Exposure, Pathway Analysis, and Cumulative Risk These

projects focus on assessments enabled by the multi-pathway and multi-chemical

nature of the NHEXAS studies.

5. Evaluation/Refinement of Exposure Models and Assessments These

projects describe the testing of existing exposure models and developing new or

improved exposure and dose models.

6. Designing Exposure Studies These projects involve examination of the

feasibility of NHEXAS concepts, methods, and approaches for the conduct of

future population-based exposure studies.

B. In the second step, four “ranking” criteria were developed and applied in a hierarchical fashion

to establish priorities for the projects within each of these six topic areas.
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1. Timing: Identifying projects that should begin in the near-term, in an intermediate

timeframe, and in the long-term was influenced by:

• Critical path issues: For example, the completeness of the analytical results should

be evaluated for each type of sample before making comparisons between

measurements.

• Sequencing issues: For example, simpler analyses should be undertaken to

understand the distributions of the measurements data before more complex

analyses of these data are performed.

• Note: This refers to the timing for initiation of research, rather than the immediacy

of regulatory needs (see Demand bullet that follows). For example, there is an

“immediate” need to begin projects with both short-term regulatory and long-term

scientific impacts that ultimately improve regulatory foundations.

2. Feasibility: The feasibility of completing any individual project depends on:

• Limitations in the NHEXAS designs and data: For example, limitations in the

designs of the NHEXAS pilot studies, types of samples and questionnaires

collected, quantity and quality of results, and in the ability to combine data sets

influence feasibility.

• Other scientific limitations: For example, limitations in the current state of the

science (e.g., the lack of cumulative risk models) and in the availability of data

(from outside the NHEXAS database), statistical methods, or models needed to

complete the analysis project will affect feasibility.

3. Applicability: The broad applicability–or relevance--of a project to important

objectives described in three other sources.

• SAB recommendations about NHEXAS: The extent to which any individual

project responds to the SAB recommendations in its advisory report (Table 2)

influences applicability.

• EPA strategic goals, as identified by the Government Performance and Results Act

(GPRA): The extent to which any individual project is relevant to EPA’s GPRA
14

objectives (Table 3) increases the significance of the exposure assessment, risk

assessment, or risk management information that may result from that project.
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TABLE 2. KEY SAB/IHEC RECOMMENDATIONS FOR THE ANALYSIS OF

NHEXAS PILOT STUDY DATA

Exposure Assessment

•critical evaluation of the potential value of meta-analysis across the three subcomponents of

NHEXAS and development of a plan for any meta-analysis

•identification of findings of considerable importance to help the Agency in some current risk

management efforts

•once descriptive and summary statistics have been completed, concentration data should be

transformed into exposure data

•integrate total exposures from all media and to estimate long-term exposures from

short-term measurements

•prototypical analyses of exposure and assessments of intervention strategies should be made

for a variety of chemicals measured

•improve the quality and utility of the databases from the three pilot studies 

- integrate databases (Region V and Arizona)

- assess the implications of the Maryland study for the Arizona and Region V study

- integrate NHEXAS results with information on criteria pollutants

• assess source-to-dose trends

Exposure Analysis

•complete QA and quality control (QC)

•conduct descriptive analyses

•test study hypotheses which can be addressed

•evaluate questionnaires and activity diaries and the relationships with measurements

•integrate total exposures across all media, and assess the relative contribution of different

sources, pathways, routes to exposure and body burden 

•identify factors related to high-end exposures and correlate exposure to various

chemicals/classes

Lessons Learned

•how to optimize the measurement and analytical approaches

•amount and nature of the new knowledge ... as it relates to the methodologies implemented

•national survey ... uses the experience of the pilot study so that the most appropriate

multimedia measurements (including questionnaires) are used

Modeling

•develop physical models that integrate exposures from different media in order to estimate

long-term exposures from short term-measurements. 

•models for identifying factors related to high-end exposures

•address model validation and refinement
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TABLE 3. RELATIONSHIP OF NHEXAS PILOT STUDY DATA TO 

ADVANCING EPA STRATEGIC GOALS IDENTIFIED IN THE 

GOVERNMENT PERFORMANCE AND RESULTS ACT (GPRA)

1. Clean Air

• NHEXAS-collected data on personal, indoor, and ambient concentrations of several air toxics can be used

to estimate exposure distributions and to verify models that predict ambient concentrations/exposure

from emissions inventory data

• NHEXAS data can contribute significantly to identifying some of the key pollutants likely to cause urban

toxics risks, to making determinations of the adequacy of existing rules in addressing risks, and to

estimating whether residual risks remain after technology-based standards are put in place for individual

source categories

2. Clean and Safe Water 

• NHEXAS data can show the distribution of exposures to disinfection byproducts (e.g., chloroform),

arsenic, and other compounds from drinking water.

• NHEXAS multipathway data can provide information on the relative source contribution of water to

exposure to the chemicals studied.

3. Safe Food 

• NHEXAS data on multipathway exposures of children to pesticides can provide the scientific foundation

for reducing uncertainties and reliance on default assumptions used by EPA in determining potential risks

to children exposed to pesticides, especially through the dietary pathway

• NHEXAS data can be used to develop and evaluate aggregate and cumulative exposure model(s) of

pesticides for infants and children.

• NHEXAS measurement-based results and probabilistic models can provide better exposure and risk

assessments for the pesticides studied

• NHEXAS provided direct measurements of dietary exposure that can be used to evaluate uncertainty in

the pesticide tolerance approach (i.e., indirect estimates of dietary exposure).

4. Preventing Pollution and Reducing Risk in Communities, Homes, Workplaces and Ecosystems

• NHEXAS measurement-based information on population distributions of exposures to the selected

pesticides and toxic substances can improve exposure assessments of communities.

• NHEXAS characterization of multiple pathways of exposures can assist the Agency in identifying highrisk pathways to target risk reduction.

• NHEXAS results will also help to evaluate the contribution of various pathways by examining blood lead

in the context of both environmental concentrations and activities.

• NHEXAS measurements of indoor air quality and total personal exposure can be used to estimate the

sources (e.g., indoor, outdoor) of the greatest exposure to chemicals studied. 

5. Better Waste Management, Restoration of Contaminated Waste Sites, and Emergency Response 

• NHEXAS data can provide baseline population exposure data to contrast with non-NHEXAS exposure

data collected at Superfund or hazardous waste sites.
17

TABLE 3 (cont’d). RELATIONSHIP OF NHEXAS PILOT STUDY DATA TO 

ADVANCING EPA STRATEGIC GOALS IDENTIFIED IN THE 

GOVERNMENT PERFORMANCE AND RESULTS ACT (GPRA)

6. Reduction of Global and Cross-border Environmental Risks

• NHEXAS data on persistent chemicals (e.g., some pesticides, limited mercury data) can be used to

understand exposure to these compounds.

7. Expansion of Americans’ Right to Know About Their Environment

• NHEXAS provided data on the distribution and predictors of exposure to selected chemicals. 

• NHEXAS can help to identify factors (environmental indicators and sources) responsible for the highest

exposures (and body burden), enabling people to identify their behaviors that contribute significantly to

exposures.

• NHEXAS data can be used to develop substantially more cost-effective community exposure study

designs, enabling others to conduct such studies in their communities.

8. Sound Science

• NHEXAS data can be used to significantly improve understanding of exposure factors that are

fundamental to conducting exposure assessments.

• NHEXAS information on multipathway exposure to a variety of compounds can be used to develop and

verify improved aggregate and cumulative probabilistic exposure models.

• NHEXAS data could be evaluated to estimate whether some of the compounds measured suggest an

emerging risk.

• NHEXAS measurements of biomarkers of exposure, together with environmental and exposure

measurements and activity information, can be used to estimate total absorbed dose and to evaluate

pathway contributions.

• NHEXAS objectives: The extent to which any individual project helps to meet

overall NHEXAS objectives and those identified for each study (based on the

July-Sept., 1995 issue of Journal of Exposure Analysis and Environmental

Epidemiology; summarized in Table 4) will further achieving NHEXAS goals.

4. Demand: Projects for which an urgent demand for the results has been identified by

the EPA’s Program Offices (e.g., aggregate pesticide exposures for Food Quality

Protection Act)
18

TABLE 4. KEY NHEXAS OBJECTIVES

• Evaluate the feasibility of NHEXAS studies for conducting future studies (e.g., better

methods and approaches)

• Document the occurrence, distribution and determinants of exposures (e.g., population

distributions of measurements, analysis of questionnaire information on sources and

activities relative to exposures)

• Understand the determinants of exposure for potential at-risk populations as a key element

in developing effective risk management strategies

• Evaluate and improve the accuracy of models developed to predict or diagnose exposure

of people to chemicals. 

As mentioned, these criteria were applied in a hierarchical fashion within each of these six

topic areas. For example, those projects with a scientific focus on Predictors of Exposure and Dose

(Table 6 on page 25), were first sorted based on the timing criterion. Next, those projects that are

needed in the near-term were sorted as to their feasibility. Subsequently, the highly feasible projects

were examined to identify those with broad applicability. Ultimately, those with high demand were

identified. The next cycle focused on those the Predictors of Exposure and Dose projects that are

needed in an intermediate-term time frame to determine their feasibility, applicability, and demand. 

No long-term Predictors of Exposure projects were identified. But had they been, the hierarchal

process of ranking for feasibility, applicability and demand would have been repeated.

The remaining strategic issue not yet discussed is the relative priority of projects across the six

topic areas. Recognizing the limitations of future resources that may be available to support these

data analysis projects and the scientific merit of these categories, we conclude that the priorities for

supporting analysis projects across the six topic areas are inherently equivalent. Thus, over the next

several years, the highest priority projects across the six areas will be funded, in priority order, within

each area. Ultimately, judgement will be required for implementation decisions, but this judgement

will be guided by the criteria and priorities discussed here.

The prioritization criteria relate to overall EPA needs. Others may have different specific

priorities that are valid for them. We expect that when the database is completed and publicized,

many scientists and organizations will find additional analyses of interest to them. For example, an
19

EPA Region or a state public health department may have an immediate need for an exposure

assessment of one chemical from only one pilot study. They might then apply their resources for this

specific analysis. A graduate student with funding may use the publically available database to test a

hypothesis for his/her dissertation, even if it is not ranked high in this strategy. Many such examples

could be given. Having this variety of thinking can be very valuable and will add to the breath of what

will be learned from NHEXAS. This value will be enhanced if the people performing these analyses

contribute to the NHEXAS web site so that others do not unnecessarily duplicate analyses and 

citations for the resultant publications are readily available to everyone. We do respectfully request

that all persons contemplating their own NHEXAS analyses carefully reflect on the priorities

described here, understanding that these analyses are likely to have a high impact on environmental

health decision making.

Any classification scheme requires compartmentalization of projects that can obscure their

interrelationships. Thus, one of the implementation goals of the ORD staff is to ensure the appropriate

degree of project integration. For example, some analyses within the area of Predictors of Exposure

and Dose provide inputs into model comparisons under Evaluation/Refinement of Current Exposure

Models and Assessments. Interdisciplinary integration with data or research outside the NHEXAS

realm is also important. For example, some of the exposure assessments based on NHEXAS data

will be compared to health effects information to create some risk assessments.

4. TOPIC AREAS AND PROJECTS

This section briefly summarizes the topic areas and the projects within them and explains the

basis for the prioritization relative to the criteria of Section 3. Each subsection contains a table of the

priorities for each project. Although the projects are listed in rank order, all projects are highly

valuable. Appendix D contains a single table that combines the priorities for each topic area. The

individual project descriptions are in Appendix E. The project descriptions are intentionally at a level

of detail that provides goals and guidance to the investigators, while allowing them the freedom to

apply their ideas in developing the details of the analyses based on the specifics of the data available
20

and their creativity. Therefore, each project has numerous options. Use of an external peer-review

process for analysis tasks performed by ORD and external scientists will assist in ensuring the quality

of the analysis approach chosen.

The first three project descriptions in each topic area contain estimates of the level-of-effort

expected for each project. Such information is subjective and only intended to provide guidance for

what resources may be needed. We chose to indicate personnel needs because they form the

predominant cost category and costs/person can vary widely across performing organizations. We

did not develop such estimates for each project because, at this time, it is not credible to make

estimates for projects that will not begin for several years and that are dependent on information not

yet available.

One overarching issue is the need to maximize utilization of resources by adhering to priorities

and avoiding unnecessary duplication of effort. Because so many analyses are going on concurrently,

the possibility of duplication arises. Insofar as the analyses are funded by ORD, internal

communication can prevent this problem. However, we are hopeful that many others will be using the

publically available database independent of ORD. As mentioned elsewhere, ORD intends to

develop and maintain an NHEXAS website that provides summaries of ongoing analyses, with

contact information, and citations to completed studies. This will provide important information to

these other scientists. Even so, it is critical for everyone working with the data sets to be

knowledgeable of the full range of analyses to ensure that the research is not redundant. Thus, we

will be developing an easy way to engage all NHEXAS analysts in communication through the

website.

4.1 DATA ANALYSIS AREA ONE: DESCRIPTIVE STATISTICS

4.1.1 Overview

This data analysis area contains research projects that describe the basic features of the

NHEXAS pilot study results, both for the measurements and for the questionnaires and activity

diaries. Residential environmental concentrations were measured for air (indoor and outdoor), tap

water, soil, house dust, and surfaces for multiple target chemicals. Corresponding personal
21

measurements were obtained for air, diet, and dermal exposures; biomarkers of exposures were

determined for blood, urine, and hair. However, not all sample types were collected for all chemicals

nor for all participants within a study. The NHEXAS studies collected information using

questionnaires for demographic and housing characteristics and potential sources of pollutants; and

used diaries for personal activities, such as duration of time spent in different locations, source- and

contact-related activities, and dietary consumption. Sampling weights have been calculated and can

be used to draw inferences to the target populations and subgroups (limited by sample sizes). These

include adjustments for nonparticipation in different elements of the study, including those providing

only questionnaire information or participating in selected measurements.

As a first step in the analyses of these data sets, information on the summary statistics for the

questionnaire and measurement results will be collected. This includes collecting and comparing

results of analyses reported by the individual study investigators and conducting additional analyses

using a common set of statistical methods, including weighted variance estimates. These studies will

provide summaries for different population groups and supply a broad range of information about

distributions (for continuous variables) or frequency of responses (for categorical variables). In

addition, the completeness of the measurements data is to be evaluated relative to the potential utility

of the data in the analysis or modeling of multipathway or multiroute exposures.

4.1.2 Developing Priorities for the Projects

Timing was first used to prioritize studies (Table 5) because of the need to understand the basic

structure of the NHEXAS data prior to conducting more complex analyses. These descriptive

analyses can be used to provide estimates of various exposure concentrations and exposure factors

for exposure assessments. These assessments often rely on point estimates or distributions obtained

from limited data sets that may not be appropriate to the populations of interest for that assessment. 

The NHEXAS results also can provide reference ranges (baseline information) for comparison to

other locations, such as Superfund sites. Another use of these results is to determine the potential

bias in estimates of national exposure factors and distributions that may result from the use of local or

regional sampling. The projects described 
22

TABLE 5. DESCRIPTIVE STATISTICS PROJECTS AND PRIORITIESa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

D-01 An Analysis of Media Concentrations, Exposure,

and Biomarkers by Demographics

N H H

D-02 Univariate Statistics for Use in Exposure and Risk

Assessment

N H M Y

D-03 Impact of Censoring and Method Sensitivity and

Precision on Multimedia Exposure Distributions and

Associations

I H H

D-04 Quantify Uncertainties in NHEXAS Data and

Assess Contribution to Model Errors

I M M

D-05 Investigate National Representativeness of

NHEXAS Sampling Results by Comparing

Measurement and Exposure Results Across the

Three Regions

I L M

aN = near term; I = intermediate term; H = high; M = medium; L = low; Y = yes.

in this section also address specific recommendations by the IHEC for conducting descriptive

analyses and examining the shapes of exposure distributions.

Simple breakdowns by demographics (Project D-01) and providing univariate statistics for

exposure and risk assessments (Project D-02) were identified to be completed first among the other

projects in this topic area. Both of these projects also were identified as being highly feasible, given

the availability of the NHEXAS data sets and current statistical methods and software. Several

Agency needs include describing differences in exposures for different population subgroups. 

NHEXAS objectives to document distributions, including those of subgroups, also are met. Thus,

Project D-01 was viewed as having slightly broader applicability than Project D-02. The next three

projects involve more complex analyses, including multiple media and pathways (Projects D-03 and

D-05), or model-based uncertainty analyses (Project D-04). Feasibility of completing these studies,

given the limitations of the NHEXAS studies, was used to prioritize them: describing the impact of

detection limits in various media (Project D-03) should be highly feasible, quantifying uncertainties

(Project D-04) was viewed as being more difficult, and comparing measurement results across the
23

three studies (Project D-05) was considered less feasible. Specific comments are provided below

for each project.

D-01 An Analysis of Media Concentrations, Exposure, and Biomarkers by Demographics — 

The goal of this project is to provide descriptive analyses of media concentrations, exposure,

and biomarkers measurements for population subgroups (age, gender, ethnicity, socioeconomic

status [SES], urban/rural, or other important groupings) in each NHEXAS study to identify

differences among subgroups and to compare distributions with other studies.

Summary analyses need to precede more complex analyses; these descriptive analyses and simple

demographic comparisons should be highly feasible. The project meets several EPA needs, related

to subpopulation differences, as well as NHEXAS objectives and SAB/IHEC recommendations.

D-02 Univariate Statistics for Use in Exposure and Risk Assessment – The goal of this project is

to develop univariate descriptive statistics (distributional information) for NHEXAS data that

can be used broadly in exposure and risk assessment and in the design of human health effects

studies.

This project develops summary statistics for those measurements and factors identified (by EPA’s

National Center for Environmental Assessment [NCEA]) as being commonly used in risk assessment,

for which data were collected in one or more of the NHEXAS pilots. The data collected by

NHEXAS can be used to better define distributions of these concentrations and exposure factors,

such as activities, time spent in specific locations, dietary intake, and product usage. Although there

are similarities between this project and Project D-01, this project is intended to support revision of

the EPA Exposure Factors Handbook, and the selection of measurements and factors analyzed may

be more limited than the previous project. Several program offices have identified access to summary

information from the NHEXAS studies for use in exposure and risk assessments as an “urgent” need.
24

D-03 Impact of Censoring and Method Sensitivity and Precision on Multimedia Exposure

Distributions and Associations – The goals of this project are twofold: (1) to examine how

method sensitivity and precision and the censoring of data below detection limits affect the

estimation of distributions and means for exposure, media concentration, and biomarker

measurements and (2) to evaluate associations among such measurements. 

The timing for some components of this project (i.e., summary of measurement sensitivity, proportion

of samples above detection limits) is near-term, although identification of measurements to represent

multiroute exposures for selected chemicals will be more complex. The feasibility is high, given the

availability of codes in the database that indicate whether each sample’s analytical results were above

the detection limits. The applicability was also high, given the need for this information before

conducting analyses (or assessments) involving multiple pathways or routes of exposure.

D-04 Quantify Uncertainties in NHEXAS Data and Assess Contribution to Model Errors – The

goal of this project is to provide uncertainty estimates within the NHEXAS database that are

available to researchers and the public, so that uncertainty is addressed consistently and does

not lead to redundant effort by modelers. The results will identify how the data uncertainties

may impact modeling uncertainties and will be illustrated with case studies.

The timing for this project is intermediate (or longer) term, based on the need to first determine the

completeness of the NHEXAS measurements for multiroute exposures (Project D-03). The first

component of the project, to identify variability and potential measurement errors (i.e., survey,

sampling, analytical), should be feasible as an extension and publication of the QA results from each

study. However, feasibility to quantify the impact of these sources of uncertainty on models may be

limited by the need to identify and apply a suitable multimedia human exposure model (or

framework).

D-05 Investigate National Representativeness of NHEXAS Sampling Results by Comparing

Measurement and Exposure Results Across the Three Regions – The goal of this project is

to evaluate the effects of using local or regional studies to provide estimates of national

exposure factors and distributions. Very few national studies are available for use in
25

development of national distributions for exposure factors or related measurements; therefore,

local or regional studies are used instead. The three NHEXAS studies provide a method for

comparing very similar studies to determine the magnitude of regional differences for various

exposure factors.

The timing for this project follows that of the projects to conduct basic summary analyses within each

study. Feasibility is limited by the number of chemicals that were measured in all three studies, by

potential differences in the methods or protocols employed (especially for sample collection), and by

differences in the target populations for some chemical classes (e.g., a limited number of children in

Arizona and Maryland studies, compared with the Minnesota study for pesticides). 

4.2 DATA ANALYSIS AREA TWO: PREDICTORS OF EXPOSURE

AND DOSE

4.2.1 Overview

This data analysis area includes research projects to analyze the relationships among the various

type of measurements (environmental, exposure, and biomarkers), questionnaires, and diaries that

were collected in the NHEXAS pilot studies. The comparisons included in this section include

measurement and questionnaire data related to

•sources, characteristics, concentrations, activities, exposures, and biomarkers; 

•multiple environmental media or exposure pathways; 

•indoor and outdoor concentrations and estimated contributions of indoor and outdoor

concentrations to integrated inhalation exposures; 

•residential environmental media concentrations and existing monitoring data (e.g., fixed sites); 

•biomarkers of internal dose and risk factors, including demographics, housing characteristics,

questionnaire data, and measures of exposure and correlations among risk factors; and 

•biomarkers and questionnaire responses and exposure and environmental media

concentrations using multivariate analysis methods. 
26

NHEXAS provides a rich source of information to support analyses of exposure and internal dose

based on data collected from questionnaires and measurements of chemicals in residential and other

environments. These analyses will be explored within each study and compared among studies.

Several of the projects involve hypotheses-testing, including hypotheses identified for the design

of the pilot studies, or structural (model-based) analyses of exposure and dose. Included is an

analysis of the relationships between measurements and estimates of dietary exposures. Other

projects involve analyses of questionnaires and activity diaries. These analyses will evaluate the

information content obtained from the questionnaires and compare that with exposure and

environmental measurements to determine the value of the questionnaire items. Regression analyses

will be used to identify the predictors of exposure. Factor analysis or principal components analysis

will be used to identify the most important questions (or groups of questions) that would be used to

analyze chemical exposures. Categorical or exploratory data analyses (e.g., classification and

regression trees [CART]) could be used to identify questions useful in identifying those who are highly

exposed, both to single chemicals or classes and to multiple chemicals. 

4.2.2 Developing Priorities for the Projects

Timing was considered relative to other projects within this area (i.e., which of these projects

should be done first), given the increasing complexity of these projects relative to the previous topic

area (Table 6). The types, complexity, and scope of proposed analyses were used to identify

Projects P-01 and P-02 as near-term. Feasibility of conducting the analyses using the NHEXAS

study data and requirements for other models or data then were used to further rank both near- and

intermediate-term projects. For projects related to biomarker analyses and interpretation (Projects

P-04 through P-06), broad applicability and demand were used to help set the priorities.
27

TABLE 6. PREDICTORS OF EXPOSURE AND DOSE PROJECTS

AND PRIORITIESa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

P-01 Analysis and Comparison of NHEXAS Exposure

Data to Residential Pollutant Sources,

Concentrations, and Activity Patterns

N H H Y

P-02 Compare Traditional Indirect Method of

Estimating Dietary Exposures with Duplicate

Diet Data and Compare Methodologies Utilized

in NHEXAS

N M H

P-03 Identifying Predictors of Exposure I H M

P-04 Risk Factors for Biomarkers of Internal Dose:

Demographics, Questionnaire Data,

Concentrations, and Exposures 

I M H Y

P-05 Determinants of Dose Measurements

(Biomarkers) from the NHEXAS Studies

I M H

P-06 Exploratory Data Analysis Methods for

Evaluating Relationships Among

Questionnaires, Exposure, Dose, and Risk

Factors

I M M

P-07 Use of NHEXAS Data To Test Assumptions

About Activity Pattern Factors and Other

Exposure Factors in EPA Risk Assessments

I L M

aN = near term; I = intermediate term; H = high; M = medium; L = low; Y = yes.

P-01 Analysis and Comparison of NHEXAS Exposure Data to Residential Pollutant Sources,

Concentrations, and Activity Patterns – The goals of this project are to (1) evaluate

hypotheses about relationships among residential pollutant sources, characteristics,

concentrations, and human activity patterns that contribute to personal exposures, especially

for high-end exposures, and (2) to determine the value of questionnaires for understanding

various aspects of exposure and the reliability and validity of the instruments used for

ascertaining these factors.

This project was identified as near-term, given its ability to help identify the major predictors

(or explanatory factors) of exposure. The feasibility should be high, given the range of questions and
28

associated measurement data and the availability of analysis methods. The project has very broad

applicability for identification of factors associated with higher exposures, relating ambient and indoor

concentrations to exposures, evaluating the value of questionnaires (and items) for understanding

public health and exposures, and classification of exposures in epidemiological studies. Demand for

this study was classified as “urgent” given several of the needs identified by IHEC, including

descriptive analyses, evaluation of questionnaires, and characterization of high-end exposures. 

P-02 Compare Traditional Indirect Method of Estimating Dietary Exposures with Duplicate

Diet Data and Compare Methodologies Utilized in NHEXAS – The goals of this project

are to (1) compare dietary exposure estimates from a dietary exposure model with direct

measurements of dietary exposure; (2) evaluate the reliability and validity of dietary intakes

determined in NHEXAS; and (3) evaluate alternative and less costly methods for measuring

dietary exposure. This will involve comparison of direct exposure data from NHEXAS

duplicate diet measurements with indirect exposure estimates derived from recorded food

consumption combined with concentrations of NHEXAS chemicals measured in other diet

studies, and of food intake rates from NHEXAS questionnaire surveys with those from the

U.S. Department of Agriculture (USDA) and the National Health and Nutrition Examination

Survey (NHANES) for comparable years, geographical regions, and population subgroups. 

This project was identified as near-term, given its potential contribution to the understanding of

dietary exposure and methods. Indirect estimates of dietary exposure, based on combining food

intake rates with residue data, have been used for regulation of pesticides and for assessing exposures

to metals and other chemicals. The NHEXAS data provide a unique opportunity for evaluation of

indirect estimates using direct monitoring data (duplicate diet) to enhance the scientific basis for

decision making. Feasibility was considered moderate, because the food diaries may require

recoding and these data then need to be linked to existing dietary concentration databases. 

Applicability is broad because this study relates to several EPA needs (e.g., Safe Food) and also

tests a basic NHEXAS study hypothesis (e.g., the adequacy of extant data and models to predict

exposure). The results also will help to evaluate survey instruments (diet diary and recall
29

questionnaire), assess the contribution of dietary exposure, and identify less costly alternatives for

dietary exposure monitoring. 

P-03 Identifying Predictors of Exposure – The goal of this project is to identify primary

predictors of exposure, using questionnaires and biological or environmental measures for use

in epidemiology studies and other studies where individuals’ exposure levels are sorted into

categories, such as high, medium, and low.

The timing for this project was identified as being intermediate-term because the proposed

multivariate analyses are likely to be more complex than those identified in the previous projects. 

Feasibility to conduct these analyses should be high, given the availability of statistical methods. The

applicability appears to be less broad, in terms of meeting multiple EPA needs, than the previous

projects but will help to meet the needs of epidemiologists, risk assessors, and risk managers who

need exposure classification methods. 

P-04 Risk Factors for Biomarkers of Internal Dose: Demographics, Questionnaire Data,

Concentrations, and Exposures – The goal of this project is to develop methods of

estimating internal dose that can be used in studies of health outcomes, based on an analysis of

the association of biomarkers of internal dose with (1) demographics; (2) questionnaire

information on behaviors, activity patterns, health indices, etc.; and (3) measures of personal

exposures and media concentrations.

The timing for this project was identified as being intermediate-term, given the broad scope and

complexity of the proposed analyses. Feasibility may be limited by the need for other models and

information (e.g., absorption and elimination rates, timing and routes of exposures) to interpret

biomarker measurements relative to dose and by the timing of the NHEXAS exposure and

environmental measurements relative to the time periods represented by the biomarkers (e.g., shortterm for blood-VOCs; long-term for blood-lead). Further understanding of the interpretation of

biomarker levels is valuable because they may be a better predictor of health outcome than

environmental concentrations, which do not account for multiple routes or for uptake/intake and

absorption processes. The ability of these markers to account for multiroute exposures gives this
30

study broad applicability in addressing EPA needs, as well as those identified by IHEC (evaluate

questionnaires, activities, concentrations, and biomarkers) and for the NHEXAS studies (distribution

and determinants of exposures; provision of baselines for biomarker distributions). Demand has been

high for information on distributions of biomarker measurements and their interpretation relative to

questionnaire information and environmental concentrations. 

P-05 Determinants of Dose Measurements (Biomarkers) from the NHEXAS Studies – The goal

of this project is to identify and evaluate environmental and questionnaire determinants of

absorbed dose and to better understand the time course and associations between exposure

and dose. Questionnaire response data will be considered as a modifier of the exposure/dose

association. This association will be evaluated further by taking into account existing

pharmacokinetic models and parameters. Methods and approaches for assessing the dermal

exposure contribution relative to the biomarker measurements are of particular importance

because dermal exposure methods are not well developed.

The time frame for this project was identified as intermediate, given the complexity of the analyses. 

Feasibility is moderate, given the need to link pharmacokinetic models and parameters with statistical

analyses. There is broad applicability for improving the ability to interpret biomarker measurements

to a range of EPA goals, IHEC recommendations (integration of exposures and relative contributions

and questionnaire analyses), and NHEXAS objectives (occurrence and determinants of exposure and

dose). Demand for these analyses appear to be less than for Project P-04.

P-06 Exploratory Data Analysis Methods for Evaluating Relationships Among

Questionnaires, Exposure, Dose, and Risk Factors – The goal of this project is to identify

the factors that contribute to high exposures, to establish relationships among these factors and

exposure magnitudes and distributions, and to understand subpopulation differences. Several

analysis methods are now available for analyzing complex data sets to identify patterns,

relationships, sociodemographic variables, important factors, and combinations of factors that

influence or affect exposure distributions. These data will be analyzed without a priori
31

decisions about relationships among the variables to generate new hypotheses regarding

environmental exposures.

This project involves more complex analytical approaches and a very broad scope that will probably

require a longer time frame for completion. Feasibility may be limited by the completeness of the

NHEXAS study data and by limitations in applying some analytical techniques to categorical

response data (i.e., questionnaires). However, the results could have fairly broad applicability by

helping to classify the NHEXAS data into variable groups and focus future exposure assessments in

national surveys, epidemiological studies, and risk assessments. Refinements could be made to the

questionnaires used in subsequent studies that reduce participant burden and study costs. This

project addresses some EPA needs, as well as IHEC recommendations for questionnaire analyses

and NHEXAS objectives to understand the determinants of exposures. 

P-07 Use of NHEXAS Data To Test Assumptions About Activity Pattern Factors and Other

Exposure Factors in EPA Risk Assessments – The goal of this project is to test assumptions

and scenarios used in current assessment procedures, to improve current exposure assessment

methodologies, and to identify factors where further study is needed. This project will

examine the use of activity pattern factors and other exposure factors in risk assessments as

they are done in EPA’s Air, Water, Hazardous Waste, Pesticides, and Toxics programs. 

Examples include (1) examining NHEXAS time/activity diaries and follow-up questionnaire

data to determine the repetitiveness (frequency) of behavior over a 6- or 7-day period and

comparing this with existing time/activity databases; (2) examining the relationship among

climate, season, level of exertion, and drinking water intake; (3) preparing exposure scenarios,

evaluating scenarios with NHEXAS data, and comparing those results to results obtained

using current exposure assessment methods, scenarios, and assumptions; and (4) using

NHEXAS data to design scripted sampling protocols for subsequent model testing or trend

monitoring.

The timing for this project was identified as intermediate, given the complexity of tasks relative to

other analyses. Feasibility was estimated to be low, given the limited resolution (time and locations)

of the NHEXAS time/activity diary used for a week-long collection period, as compared to more
32

detailed recall diaries that have been used for a 1-day period and without the additional requirements

involved in a monitoring study. The analysis of activity patterns could be used to test assumptions and

scenarios used in current assessment procedures, to improve the current EPA methodologies, and to

identify factors where further study is needed. Applicability was considered moderate for addressing

EPA needs, as well as IHEC recommendations and NHEXAS objectives.

4.3 DATA ANALYSIS AREA THREE: SPATIAL AND TEMPORAL

VARIABILITY

4.3.1 Overview

Environmental media concentrations of chemicals and exposure patterns of individuals vary

over both space and time. NHEXAS studies have collected extensive data on environmental

concentrations, exposures, questionnaires, time activity, and dietary patterns from participating

subjects and households selected from many different communities in EPA Region V, Arizona, and

Maryland. Moreover, the Maryland component of the NHEXAS study has gathered exposure,

activity, and dietary survey data on a large cohort of subjects over multiple months and seasons and

over seven consecutive days in each cycle. Thus, the NHEXAS database (particularly the Baltimore

Study) offers a unique opportunity to examine the spatial and temporal variability in human exposures

to both single and multiple chemicals and to identify key factors that effect inter- and intraindividual

variability in exposures. 

The analysis of temporal variability in exposures and concentrations will include analysis of both

single and multiple chemical concentrations measured in each of the environmental media by the three

NHEXAS studies. Both within- and between-study variability will be examined. Temporal variability

in human behaviors and dietary patterns will be analyzed and interpreted in relation to observed

changes in the exposure patterns over time. Specifically, NHEXAS Maryland dietary and activity

pattern data will be used to develop predictive relationships between single-day and longer term

observations. This analysis will determine the reliability of using short-term measures of exposure in

the assessment of long-term or chronic exposures of individuals and populations. 
33

NHEXAS data from all three studies also will be used to investigate the spatial variability in

concentrations exposures, doses, and activity patterns. Geographical factors (i.e., differences

because of various spatial aggregations, states versus counties, rural versus urban) and climatic

factors influencing these measurements will be evaluated. The spatial and temporal analysis of the

NHEXAS data will be used to characterize the variance components of NHEXAS data, including the

inter- and intrapersonal, temporal (e.g., integration time, seasonal, weekly), activity-related, and

spatial variabilities by sample size for each of the pollutants by pathway, medium, and integrated total

exposure. Results will be used to optimize future NHEXAS-like study designs. Finally, the results

from these analysis and the NHEXAS database will be used to develop and evaluate models for

quantifying within- and between-subject variability in pesticide exposures and biomarker

concentrations.

4.3.2 Developing Priorities for the Projects

Seven projects were identified in this topic area. The ranking scheme and criteria described

earlier—timing, feasibility, and broad applicability—were used to rank the projects in this area. 

Table 7 provides the rankings, and the following sections discuss the rationale for the rankings. Once

again, relative timing was considered as the first criterion to establish rankings for the projects in this

research area. Many of these investigations can be started in the near term, when the NHEXAS data

sets are available (Projects ST-01 through ST-04). The methodologies and expertise are available to

start these projects immediately. However, Project ST-01 was the highest ranked project because it

scored best in all categories (timing, feasibility, and broad applicability). Second-ranked Project ST02 also received the highest rankings in terms of timing and feasibility. However, it does not have the

broad applicability that Project ST-01 has because it focuses solely on the temporal aspects of

dietary and activity behavior. The other two projects, which were ranked highest for the timing

criteria (Projects ST-03 and ST-04), both received a medium feasibility criteria ranking because

comparisons of personal exposures with point sources cannot be accomplished without the

cooperation of the principal investigators of the various NHEXAS consortia who need to maintain the

anomymity of the location of the subjects.
34

Projects ST-05 and ST-06 were ranked as intermediate projects in terms of timing because of

the complexity and scope of the analysis required for their successful completion. Also, this sequence

of rankings is consistent with the philosophy of completing simpler building blocks before more

complex tasks are undertaken.

The project that ranked last in terms of timing was ST-07. This project requires the

development and refinement of pharmacokinetic models. 

TABLE 7. SPATIAL AND TEMPORAL VARIABILITYa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

ST-01 Temporal Variability in Exposure Concentrations

and Aggregate Exposure Using NHEXAS Data

N H H

ST-02 Use NHEXAS Dietary and Activity Pattern Data

To Develop Predictive Relationships Between

Single Day Observations and Long-Term Patterns

of Behaviors

N H M

ST-03 Characterization of the Variance Components of

NHEXAS Data to Optimize Future Designs

N Mb H

ST-04 Spatial Variability N Mb H

ST-05 Investigate Stability of Individuals in Population

Exposure Ranks Over Time

I H M

ST-06 Spatial and Temporal Variability in Multichemical

Exposure

I Mb H

ST-07 Development and Evaluation of Models for

Interpreting and Quantifying Inter- and

Intraindividual Variability in Pesticide

Exposure/Dose Using NHEXAS Data.

L M H

aN = near term; I = intermediate term; H = high; M = medium; L = low; Y = yes.

bSpatial variability can be determined on national, regional, and community bases when the NHEXAS data

 sets are available. However, the exact location of NHEXAS participants will not be included in the

 NHEXAS data sets to protect the confidentially of the individual participants of the study. Thus,

 comparisons of personal exposures with point sources cannot be accomplished without the cooperation of

 the principal investigators of the various NHEXAS consortia. Therefore, the criterion of feasibility was

 ranked medium for these projects, as compared to other projects without such concerns.
35

ST-01 Temporal Variability in Exposure Concentrations and Aggregate Exposure Using

NHEXAS Data — The goal of this project is to determine optimum strategies and designs

for future exposure investigations. Questions to be addressed include when is it possible to

estimate exposure from a single set of cross-sectional measurements, and what is the

optimum number of such measurements that must be made for each pollutant medium class

and for total exposure? Of interest is an understanding of the temporal span of the

toxicological effect (i.e., What is the exposure duration of interest? Does variability occur

over such a duration?).

This project has important implications for risk assessment because it will help account for uncertainty

because of intraindividual variability over time and the factors that influence that variability. Most

personal exposure measurement data are collected over a relatively short period of time (e.g., a day

or week). However, exposure scientists often are interested in chronic individual exposure

distributions (e.g., a season, a year, or even 70 years) for risk assessments and for the mitigation of

unwanted exposures. In the past, exposure scientists often were forced to use population exposure

distribution data (a large number of individual snapshots sampled once at various times) to attempt to

predict individual distributions. This project has implications for epidemiology because it will help

reduce uncertainty because of misclassification resulting from bias introduced by failing to account for

temporal variability in exposure indicators for a given individual. In addition, it will help determine

optimum strategies and designs for future national exposure studies.

ST-02 Use NHEXAS Dietary and Activity Pattern Data To Develop Predictive Relationships

Between Single-Day Observations and Long-Term Patterns of Behaviors — The goal

of the project is to describe the relationship between short- and long-term measurements of

exposure-related behaviors that can be used in models of long-term exposures. This will be

accomplished through the use of statistical techniques to determine the relationships between

measurements of exposure-related behaviors (e.g., dietary and activity patterns) on a single

day and in subsequent longitudinal measurements. Therefore, the short-term relationships

will be used to develop predictive models of longer term behaviors. Such data are critical to

the accurate estimation of dose rates over periods longer than a single day.
36

This project was ranked second because of timing and feasibility considerations (it received the

highest scores possible in these categories). The ability to predict long-term behaviors from

short-term observations is extremely important to understand exposure patterns over time. However,

this project does not have the broad applicability of that of Project ST-01. 

ST-03 Characterization of the Variance Components of NHEXAS Data To Optimize Future

Designs — The goal of this project is to characterize the variance components of NHEXAS

data, including the inter- and intrapersonal, temporal (e.g., integration time, seasonal,

weekly), activity-related, and spatial variabilities by sample size for each of the pollutants by

pathway or medium and by integrated total exposure. Results will be used to optimize future

NHEXAS design. Exposure data from each of the three NHEXAS studies will be analyzed

to determine the inter- and intrapersonal, temporal, and spatial variabilities in exposure

distributions. Analysis will be performed by pollutant, both pathway-specific and as

integrated total exposure, as well as by subpopulation. Variabilities will be assessed using

standard statistical approaches, including the coefficient of variation and one-way analysis of

variance (ANOVA) and mixed model approaches. Graphical techniques will be used to

evaluate and determine appropriate pollutant- and media-specific sampling strategies. 

As possible, pollutants will be grouped based on identified appropriate sampling strategies. 

This project should be limited to representatives of the various chemical classes (e.g., metals,

pesticides, VOCs).

This project was rated highly in terms of timing and broad applicability. The proposed project

directly addresses SAB concerns and, as a result, will improve substantially the ability to optimize the

design of future NHEXAS and other exposure studies. It will incorporate findings from each of the

three NHEXAS consortia and will allow the sampling plan of each consortium to be examined in a

systematic and quantitative manner. However, the spatial variability aspects of this project give it a

medium feasibility rank because comparisons of personal exposures with point sources cannot be

accomplished without the cooperation of the principal investigators of the various NHEXAS

consortia (see Table 7 note).
37

ST-04 Spatial Variability — The goals of this research are to identify spatial and geographic

factors contributing to high exposures for consideration in exposure assessment, to determine

representativeness of local and regional data for use in assessments of other regions, and to

identify geographically defined point and area sources. These analyses will help assessors

understand the geographic variability of pollutant concentrations and exposures and the

impacts of such things as population density, climate, elevation, and local cultural factors. It

also will examine the impact of identifiable, geographically located sources on exposure

levels. Information on spatial variability also will contribute to the more efficient design of

future studies.

This project was highly rated in terms of timing and broad applicability. However, the spatial

variability aspects of this project give it a medium feasibility rank because comparisons of personal

exposures with point sources cannot be accomplished without the cooperation of the principal

investigators of the various NHEXAS consortia (see footnote for Table 7).

ST-05 Investigate Stability of Individuals in Population Exposure Ranks Over Time — This

project will investigate the effect of using cross-sectional studies on estimates of exposure

factor distributions. Cross-sectional studies are cost efficient because they collect minimal

observations per individual, but they provide no indication of temporal variability. Measures

of intraindividual temporal variability do not necessarily tell the complete story, as individuals

may vary in concert because of factors such as seasonal changes. It is also useful to

examine the stability of individual’s position or rank in the population exposure distribution to

determine how this stability influences the predictive ability of various exposure distribution

parameters. This will be accomplished by identifying feasible and relevant variables from

NHEXAS for study, developing and evaluating methods for examining temporal variability

(and stability) of individuals, and through the use of mixed models to develop repeated

measure, temporal correlation estimates.

Timing of this project was rated intermediate, resulting from the complexity of the task because of the

suggested approach (i.e., identification of relevant variables and the need to develop methods to
38

examine temporal variability and stability and models to provide repeated measure, temporal

correlation estimates). 

ST-06 Spatial and Temporal Variability in Multichemical Exposure — The goal of this project

is to characterize the magnitude and variability of exposure to multiple chemicals measured in

all environmental media by the three consortia. This study will provide some of the first

information on multichemical and multipathway exposures required for cumulative risk

assessments. The suggested approach is to examine multiple chemical exposure, first for

each route of entry and second for aggregate exposure. 

The need to assess risks of cumulative chemical exposures is well recognized within the scientific and

regulatory communities. Little information is available for such assessments. Analysis of the temporal

and spatial aspects of the NHEXAS data is important to reduce uncertainty in the exposure

estimates for these assessments. However, methods and data to support cumulative chemical

exposure generally are lacking at this time. In addition, the spatial variability aspects of this project

give it a medium feasibility rank because comparisons of personal exposures with point sources

cannot be accomplished without the cooperation of the principal investigators of the various

NHEXAS consortia (see footnote for Table 7). 

ST-07 Development and Evaluation of Models for Interpreting and Quantifying Inter- and

Intraindividual Variability in Pesticide Exposure/Dose Using NHEXAS Data — The

goal of this project is to develop, test and evaluate, and make available to EPA and the

scientific community at large, a mechanism-based computational tool for characterizing and

quantifying inter- and intraindividual variability (i.e., cross-sectional and longitudinal

variability) in pesticide exposures/doses of human populations. This project will analyze

cross-sectional and longitudinal biomarker and exposure data for pesticides considered in

NHEXAS (such as chlorpyrifos and atrazine) to develop and test population-based

pharmacokinetic (i.e., pharmacostatistical) models that explicitly discern and quantify intraand interindividual variability in human doses.
39

Quantitative characterization of inter- and intraindividual dose (and corresponding exposure) to

common pesticides will reduce the uncertainty in risk assessments. The mechanistic approach to be

developed and evaluated should be applicable to a wide range of exposure situations and U.S.

population segments. However, this was deemed a long-term project because the development and

refinement of pharmacokinetic models is required. 
40

4.4 DATA ANALYSIS AREA FOUR: AGGREGATE EXPOSURE,

PATHWAY ANALYSIS, AND CUMULATIVE RISK

4.4.1 Overview

This data analysis area addresses exposure via multiple pathways and risks from exposure to

more than one environmental agent. EPA risk assessments are evolving from a focus on single

environmental agents and, often, a single medium to assessments of total risk from exposure to

multiple chemicals via multiple pathways. NHEXAS was designed as a multipathway, multichemical

exposure study, which will provide the data to test many hypotheses related to aggregate exposure

and cumulative risk. Aggregate exposure is defined for purposes of this strategy as total exposure to

a single environmental agent. The term “cumulative risk” is used in different ways by different

programs in EPA. It may be used to mean risk from exposure to a set of environmental agents that

have the same health endpoints or modes of action, the risk from exposure to all such agents in the

environment regardless of endpoint or mode of action, or in the broadest sense, the risk from all

environmental stressors and their interaction with genetic factors. NHEXAS provides a rich database

of multiple measurements of environmental and biological concentrations of chemicals and personal

data on individual activity patterns that will help in the study of many of these issues.

4.4.2 Developing Priorities for the Projects

Four projects were identified in this topic area (Table 8). The ranking scheme and criteria

described earlier—timing, feasibility, broad applicability, and demand for results—were used to rank

the projects. The two near-term projects (Projects AE-01 and AE-02) are those for which

techniques are available to analyze the NHEXAS data and to achieve the desired results. These two

projects then were sorted by feasibility. Project AE-02 was rated lower for feasibility because it

requires comparison of data from separate NHEXAS studies, which may not always be directly

comparable. The multipathway exposure model (Project AE-03) is rated intermediate for timing. 

Development of probabilistic multipathway models is complex and requires the preliminary

assessments of Project AE-01, as well as completion of exposure analysis projects, to complete the

model. The cumulative risk project (Project AE-04) is considered long-term. Cumulative risk

assessments are highly complex. Some parts of the 
41

TABLE 8. AGGREGATE EXPOSURE, PATHWAY ANALYSIS,

AND CUMULATIVE RISKa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

AE-01 Aggregate Exposure N H H Y

AE-02 Comparison of Children’s and Adults’

Exposures to Pesticides and Other

Chemicals in the Region V, Arizona, and

Maryland Studies

N M H Y

AE-03 Construction of an Empirical

Multimedia/Multipathway Exposure

Distribution Model Including Temporal

Variability Based on NHEXAS Data

I M M

AE-04 Cumulative Risk from Exposure to NHEXAS

Chemicals

L M H

aN = near term; I = intermediate term; H = high; M = medium; L = low; Y = yes.

project, such as examination of correlations among exposures to different chemicals can be examined

in the short term, but the overall project will take considerable time to accomplish.

AE-01 Aggregate Exposure — The goal of this project is to estimate multiroute, multipathway

exposures and risks from exposure to single NHEXAS target chemicals. Environmental and

personal concentration data and questionnaire data, supplemented by data from other

sources and professional judgment will be used to estimate total exposure for each individual

respondent. Existing models will be used to combine data to estimate aggregate exposure as

a total absorbed dose. Total absorbed doses will be compared to biomarker data. 

Absorbed doses for each individual will be disaggregated by pathway, allowing identification

of the contributions of each pathway to absorbed dose. Contributions of exposure factors

(e.g., activity patterns, dietary intakes, season, climate) to high-end exposure will be

investigated by comparing factors to total absorbed dose or biomarkers. Risks of adverse

health outcomes will be estimated using standard EPA methods and risk factors from EPA’s

Integrated Risk Information System (IRIS).
42

This project is near term and can be started as soon as the NHEXAS database is available. 

Aggregate exposure assessments have been conducted for many years in ORD and in multimedia

EPA programs, such as the Hazardous Waste Program, the Toxics Program, and, more recently, the

Pesticides Program. The expertise and methodology are available to start this project immediately.

Feasibility is high, given that the NHEXAS studies were designed specifically to assess total

exposure. There will be data gaps for some parts of the exposure model, but missing information can

be obtained from other sources and supplemented by professional judgment where necessary. The

project has broad applicability. It will provide information on important pathways of exposure for

particular target chemicals, identify pathways or exposure factors that have not been considered in

assessments, and may show that some pathways are not as important as they were believed to be. 

Parts of this project could be characterized as “urgent” in the sense that the results will be useful to

ongoing EPA programs, such as the Pesticides and Air programs.

AE-02 Comparison of Children’s and Adults’ Exposures to Pesticides and Other Chemicals in

the Region V, Arizona, and Maryland Studies — The goal of this project is to conduct

aggregate exposure and cumulative risk assessments that compare children’s and adults’

exposures to NHEXAS target chemicals. The Minneapolis-St. Paul, MN, study of children

aged 3 to 12 will provide the data on children. The Region V and the Arizona studies will

provide the data on adults and a small number of children. Systematic procedures for

comparing the data across studies will be developed. Many different endpoints for children

and adults can be compared: biomarkers, personal exposure measurements (e.g., dietary

intakes of chemicals per unit body weight), activities, and absorbed doses by single or

multiple pathways. Health risks also will be assessed and compared using appropriate

toxicity values. 

This project is rated a near-term project for the same reasons given for Project AE-01. Feasibility is

rated medium for two reasons. First, children’s exposures in the Minnesota study may have to be

compared to adults’ exposures in Region V and Arizona. The Arizona study used different sampling

protocols in some cases, and, therefore, comparisons may not always be possible. Second, in most

cases, toxicity measures for childhood exposures and endpoints may not be available because of lack
43

of data. Thus, it may not be possible to make a real comparison of age-related risk but, rather, only a

comparison of exposure. The project is rated high for broad applicability because all EPA programs

are interested in the conditions under which children are at greater risk than adults from exposure to

environmental contaminants. Two recent statues, FQPA and the Safe Drinking Water Act

Amendments of 1996, specifically require EPA to consider risk to children in regulatory actions. This

study will provide comparisons of exposures and help identify the exposure pathways and factors that

contribute to the greatest differences between children and adults. For programs such as the Office

of Pesticide Programs (OPP) residential exposure programs, this comparison of children and adults

could be considered urgent. 

AE-03 Multi-Pathway Exposure Modeling — The goal of this project is to develop multipathway

models for NHEXAS target chemicals. Current multipathway exposure models are based

on studies that usually were limited to a single medium and generally lacking in longitudinal

data. Existing models will be enhanced to allow use of empirical multivariate distributions

derived from NHEXAS data. Temporal variability will be incorporated into the models

using the Maryland data.

This project is ranked as intermediate because some preliminary exposure analysis will have to be

conducted prior to development of a comprehensive model. Feasibility is rated medium. The

development of the model will require the integration of the Maryland longitudinal study with the

cross-sectional studies in Arizona and Region V. Problems of different sampling protocols will arise. 

It will be somewhat difficult to integrate children’s scenarios into the model. Although of some

interest to the various programs, a multipathway exposure model is more immediately useful as a

research project that integrates results of many of the other projects described in this strategy. The

project will extend empirical models to include temporal variability, allowing for the estimate of

exposure distributions over a 1-year period. The likelihood of developing a complex multipathway

aggregate exposure model that could be used for a wide number of chemicals may be somewhat

limited because each chemical has a different set of exposure scenarios, and incorporation of all

possible scenarios would be very labor intensive. In addition, it is difficult to update the model as

new data becomes available. Thus, EPA programs use general models for screening purposes, but
44

usually develop their own models for more intensive assessments. This project is ranked below the

others as having somewhat less applicability across EPA. 

AE-04 Cumulative Risk from Exposure to NHEXAS Chemicals — The goal of this project is to

examine cumulative risks of exposure to more than one NHEXAS target chemical. 

Multivariate statistical methods will be used to determine whether concentrations in personal

air, dust, diet, and biological samples co-vary across subjects for different chemicals. 

Groups of NHEXAS chemicals will be identified that are appropriate for cumulative risk

assessment, based on factors such as common toxicity endpoints and like modes of action. 

If data are available, synergistic and antagonistic interactions will be taken into account. 

Otherwise, additivity will be assumed. EPA guidance on assessment of mixtures will be

followed. This project calls for innovative approaches to using the NHEXAS data in

assessing the impact of exposures to multiple chemicals.

Methods and data to support dose-response assessment for mixtures of chemicals generally are

lacking. There are a few cases where assessments have been done for chemicals with common

modes of action (e.g., dioxin-like compounds, organophosphate pesticides). In general, however,

most such assessments tend to focus more on aggregate exposure than on the risk component of the

assessment. There are few methods for assessing cumulative risk for chemicals with different

endpoints. Therefore, this project is ranked as a long-term project. The feasibility is rated medium. 

The NHEXAS database will support the aggregate exposure analysis required for cumulative risk

assessment. The dose-response data are probably available now for many chemicals. If additivity is

assumed, a cumulative risk analysis of some sort might be feasible. However, success likely will

increase if the project is delayed until some additional guidance and methods have been developed. 

Cumulative risk assessments are rated high for broad applicability to all program offices. These

analyses will provide insights into whether high exposure to one chemical in a class correlates with

high exposure to others and will allow comparison of chemicals across classes. The analysis will

contribute to development of guidelines for cumulative risk assessment. This area is ranked below the

aggregate exposure project because that project is likely to provide analyses that can be used

immediately in EPA assessments.
45

4.5 DATA ANALYSIS AREA FIVE: EVALUATION/REFINEMENT OF

CURRENT EXPOSURE MODELS AND ASSESSMENTS

4.5.1 Overview

NHEXAS studies have generated a rich database on some source emission characteristics,

environmental media concentrations, time-activity and dietary patterns, and individual measures of

exposure and dose. Thus, the NHEXAS database offers a unique opportunity to test existing

exposure models and to develop new or improved exposure and dose modeling methods. This topic

area includes a number of proposals on evaluating and developing human exposure and dose models

by utilizing the NHEXAS database. 

One of the main objectives of the NHEXAS pilot studies was to compare NHEXAS exposure

measurements with exposure projections derived from exposure models and data that were available

prior to conducting the NHEXAS studies. Comparison of pre-NHEXAS study model results with

data and findings from the NHEXAS study will allow both the evaluation of the current exposure and

dose models and the implementation of research to refine these models in areas where significant

discrepancies are observed. This analysis will involve evaluating the results from the multimedia

multipathway population exposure models for benzene, lead, and chlorpyrifos that were developed

using only the information available prior to the NHEXAS study measurements. Following these

evaluations, the pre-NHEXAS models will be updated using the information collected during the

NHEXAS studies. NHEXAS data also will be used to evaluate other existing or emerging air quality

and multimedia models, such as the Hazardous Air Pollutant Exposure Model (HAPEM4) used in the

recent National Air Toxics Assessment (NATA) study, the Multimedia Pollutant Assessment System

(MEPAS), Hazardous Waste Identification Rule, Stochastic Human Exposure and Dose Simulation,

Modeling Environment for Total Risk Studies, CalTOX, Total Risk Integration Methodology

(TRIM), and LifeLineTM, etc. In addition, NHEXAS data will be used to evaluate the limitations of

the current screening methods or models used to make regulatory decisions for Superfund sites,

pesticide regulations, and emissions to air or water.

Development of new or refinement of existing multimedia multipathway models also requires

detailed information on various model parameters, such as ingestion rates, source strengths, air

exchange rates, etc. In addition to generating average estimates for these parameter values, more
46

complete characterization of ranges and uncertainties associated with these model parameters are

beneficial to most of the current probabilistic exposure models. Following the model evaluation

project, the plan is to develop model input parameter distributions using the NHEXAS monitoring,

questionnaires, time-activity, and survey data. Specific emphasis will be placed on key exposure

parameters that are likely to contribute to high-end exposures. Related analysis projects will examine

the nature and magnitude of uncertainties in the NHEXAS data, and how they may contribute to

modeling errors. Finally, NHEXAS data on biomarker concentrations will be analyzed to develop

new methods for reconstructing individual exposure profiles using questionnaires and time-activity

data. Several assumptions regarding the route and timing of dose will be studied in estimating

exposure profiles. Children, as well as the general population, will be considered during all of these

investigations.

4.5.2 Developing Priorities for the Projects

TABLE 9. EVALUATION/REFINEMENT OF CURRENT EXPOSURE MODELS AND

ASSESSMENTSa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

M-01 Compare Pre-NHEXAS Model Results

with NHEXAS Measurements

N H H Y

M-02 Comparison of NHEXAS Findings with

NATA Estimates for Ambient Air Levels

and Exposures for Selected VOCs and

Metals

N H/M H Y

M-03 Develop Model Parameters from

Qualitative and Quantitative NHEXAS

Monitoring Data, Questionnaires,

Time/Activity, and Survey Data

N M H

M-04 Evaluate Implications of NHEXAS

Results for Existing Chronic Exposure

Assessment Methodologies

I H/M H Y

M-05 Evaluation of Existing Multimedia

Models Using the NHEXAS Data Set

I M H

M-06 Quantify Uncertainties in NHEXAS Data

and Assess Contribution to Model

Errors

I M M

M-07 Reconstruct Exposure and Dose Profiles

from Biomarker Data Utilizing

Questionnaire and Environmental

I M M
47

Measurements

aN = near term; I = intermediate term; H = high; M = medium; Y = yes.

Seven projects were identified in this topic area (Table 9). The ranking scheme and criteria

described earlier (timing, feasibility, broad applicability, and demand for results) were used to rank

the projects. Timing was considered relative to other projects within this area (i.e., which of these

projects should be done first), given the increasing complexity of these projects relative to the other

topic areas. This assumes that some of the simpler modeling-related analyses would be conducted in

conjunction with other descriptive statistics and mutivariate analysis projects, and that these results

would be available to the modelers. The types, complexity, and scope of proposed analyses were

used to identify three projects (Projects M-01, M-02, and M-03) as near-term. Feasibility of

conducting the analyses using the NHEXAS study data and requirements for other models or data

then were used to further rank both near- and intermediate-term projects (e.g., Project M-02 versus

Project M-03, and Project M-04 versus Project M-05). After feasibility, broad applicability and

level of demand (or urgency of this information to EPA) were used as criteria to rank near-term

projects within the same category of timing or feasibility (e.g., Project M-02 versus Project M-03). 

Likewise, for the three intermediate-term projects related to evaluation of existing multimedia models

or uncertainty or biomarker analyses (Project M-05 versus Project M-06 and Project M-07), broad

applicability was used to help set the priorities. Table 9 provides the rankings, and the following

section describes the rationale for these rankings.

M-01 Compare Pre-NHEXAS Model Results with NHEXAS Measurements — The goal of this

project is to compare pre-NHEXAS model results for benzene, lead, and chlorpyrifos with

NHEXAS measurements. If models and data compare well, this provides an evaluated

model for use in predicting human exposures to these pollutants. These models and methods

then can be applied to populations outside of the NHEXAS study region. Differences

between measured and modeled results can be used to improve model predictions and to

provide information on limitations in the use of disparate studies. Overall, this comparison will

provide confidence in using models to estimate multimedia exposures and will allow updating
48

pre-NHEXAS models with information obtained from the NHEXAS program measurement

data. 

This project ranked first because of its importance in testing one of the important NHEXAS study

hypothesis regarding testing pre-NHEXAS study models against the data obtained from the

NHEXAS program. This analysis project also responds to several IHEC suggestions pertaining to

exposure model validation and refinement and integrating exposures from different media. It also

provides a tool for identifying factors related to high-end exposures among sensitive and general

population groups. This project can be started in the near term as soon as the NHEXAS database

becomes available because the pre-NHEXAS study models for benzene, lead, and chlorpyrifos have

been completed. For these three chemicals, the project has high feasibility because they have

sufficient number of detects in the various media sampled during the NHEXAS study. This project

will have broad applicability. It will provide information for specific program offices on important

pathways of exposure for a particularly important pesticide, a metal, and a VOC. The preNHEXAS study models will provide EPA with new probabilistic aggregate exposure assessment

models and help to advance the population exposure and dose assessment methodology. In addition,

this analysis project may reveal important pathways or exposure factors that have not been

considered in previous assessments; and also may show that some pathways are not as important as

they were believed to be. This project is characterized as urgent because ORD and various program

offices (e.g., OPP, Office of Air Planning and Standards [OAQPS]) are currently involved in the

analysis and modeling of exposures to chlorpyrifos, lead, and air toxics. The models also will

characterize exposures of children and other sensitive or highly exposed populations. This is

particularly important for EPA under the FQPA for assessing acute and chronic exposures to

children.

M-02 Comparison of NHEXAS Findings with Cumulative Exposure Project Estimates for

Ambient Air Levels and Exposures for Selected VOCs and Metals — The goal of this

project is to (1) compare patterns and trends in monitored neighborhood ambient air levels of

VOCs and metals as well as available biomonitoring data to the annual average estimates of
49

the same compounds derived through NATA and (2) evaluate the relevance of the NATA

model predictions to the types of exposure situations characterized in NHEXAS.

This is a near-term project with a high-to-moderate degree of feasibility and high applicability and

relevance to EPA’s air toxics program. It deals only with the air media and the inhalation route. The

analysis will be feasible only for a subset of VOCs and metals that have been detected in the

NHEXAS air samples. The monitoring duration and frequency and the location of samples collected

in the NHEXAS study also may restrict a more complete evaluation of NATA model results. Spatial

and temporal aggregations of the NHEXAS data most likely will be required.

M-03 Develop Model Parameters from Qualitative and Quantitative NHEXAS Monitoring

Data, Questionnaires, Time/Activity, and Survey Data — The goal of this project is to

develop exposure model parameter (e.g., ingestion rates, emission rates) values, ranges, and

distributions, making use of both quantitative and qualitative data generated in NHEXAS. 

Exposure parameters will be developed in accordance with the current state-of-the-art

exposure assessment and corresponding model input requirements. Specific emphasis will be

placed on key exposure parameters common in multimedia exposure assessments and those

that are likely to contribute to high-end exposures.

This project is ranked third because it has a moderate level of feasibility of achieving all of its goals. 

Ideally, some aspects of this project may need to be deferred until certain basic descriptive statistics

or exploratory analyses of the data are completed. However, analysis of exposure factors and survey

data on known model input parameters can be initiated in the near term. This project has high

significance. Multimedia models currently developed by EPA and other groups require exposure

factor information in the form of distributions. This project will improve existing exposure parameter

distributions used in models and also evaluate the utility of questionnaires for quantitative exposure

analysis.

M-04 Evaluate Implications of NHEXAS Results for Existing Chronic Exposure Assessment

Methodologies — The goal of this project is to take the dose estimates from personal

monitoring or biomarker measurements and compare them to those predicted from EPA
50

screening methodologies (also referred to as Tier 1 or Initial Tier assessments). Examples of

these methods include recommended exposure models under the Superfund program and the

residential standard operating procedures (SOPs) developed by EPA’s OPP. Screening

models (sets of algorithms) are used widely to make preliminary decisions for Superfund sites,

pesticide regulations, and the evaluation of emissions to air and water. However, high quality

and reliable multimedia monitoring data to validate these models are virtually nonexistent in

the literature, and, as such, the opportunity to test screening models, even on a qualitative

scale, is rarely available. NHEXAS data will allow for testing and evaluating these screening

level models and methods currently used by EPA. 

This project is ranked lower than the ones above mainly because of timing considerations. Projects

M-01, M-03, and others, such as Projects D-01 and D-02, are expected to precede this fourth

ranked modeling project. Projects D-01 and D-02 , for example, will develop the basic statistical

summaries on personal exposure monitoring and biomarker data that will be used as inputs for this

modeling project. Likewise, Projects M-01 and M-02 will be generating the necessary exposure

factor, dietary survey, time-activity, and environmental concentration information needed to initiate

this project. This project is quite feasible, depending on the pollutant type and the media selected. 

Measurements that are below the limits of detection for certain chemicals may limit the utility of this

project. However, this project has broad applicability and high demand within EPA. Both chronic

and acute exposure and risk assessments conducted by the program offices (e.g., Office of Solid

Waste and Emergency Response, OPP) will benefit from the results of this project. 

M-05 Evaluation of Existing Multimedia Models Using the NHEXAS Data Set — The goal of

this project is to evaluate the existing multimedia human exposure and dose models using the

NHEXAS data set. High-quality and reliable multimedia monitoring data are virtually

nonexistent in the literature, and, as such, the opportunity to test existing models, even on a

qualitative scale, is rarely available. Several multimedia models have been developed, or are

under development, that predict media concentrations in residential environments based on

inputs such as source characterization, fate, and transport. Examples of models that are

proposed to be evaluated include TRIM, MEPAS, Cumulative and Aggregate Risk
51

Evaluation System (CARES), LifeLineTM, and Consumer Exposure (CONSEXPO), as well

as other linked and nested compartmental models.

Timing of this project is ranked intermediate because of complexity and diversity of the task.

Moreover, some of the models mentioned above are still in developmental stages and may not be

available for complete evaluation for another 2 to 4 years (e.g., CARES, TRIM). Relevant variables,

exposure factors, and other model inputs have to be developed first also. Feasibility of this project

also depends on the type of model selected and the feasibility of inputs or information that can be

obtained from the NHEXAS study. The project has broad applicability within EPA because ORD

and program offices are currently engaged in developing or refining a number of different exposure

and dose models for pesticides, metals, particulate matter, air toxics, PAHs, etc. 

M-06 Quantify Uncertainties in NHEXAS Data and Assess Contribution to Model Errors — 

The goal of this project is to address an important component of most population exposure

models dealing with proper characterization of parameter and model input uncertainties. This

analysis will provide a comprehensive set of uncertainty estimates based on the NHEXAS

database, so that uncertainty is addressed consistently and does not lead to redundant effort

by modelers. The project also will examine how the data uncertainties may impact modeling

uncertainties and illustrate with case studies. Inclusion of uncertainty estimates and

descriptions in exposure assessments and models will improve the risk assessment process

and will inform the scientists, the public, and the regulatory community of possible limitations

in the use of the data.

Timing of this project was rated intermediate, again because of the complexity of this task and the

suggested approach (i.e., identification of relevant factors, data sets, correlations among variables,

and spatial and temporal dependencies among the various parameters and values). The project has a

medium level of feasibility and moderate applicability because proper characterization of uncertainties

will be limited by the NHEXAS study design. Namely, the types and numbers of measurable or

quantifiable variables available for analysis will vary by NHEXAS region and pollutant type.
52

M-07 Reconstruct Exposure and Dose Profiles from Biomarker Data Utilizing Questionnaire 

and Environmental Measurements — The goal of this project is to develop and evaluate a

methodology that provides realistic estimates of the dose and exposure associated with a

biomarker measurements as a function of the types of exposure that occurred. The

relationships among environmental measurements, time/activity data, and biomarker levels will

be investigated, with the goal of classifying exposure scenarios into steady-state cases (e.g.,

from long-term average exposures) and intermittent events. There are several assumptions

regarding the route and timing of dose that need to be addressed in making these estimates,

and the questionnaires and time/activity data will be used to make these determinations. The

analysis will attempt to focus on the exposures of children, in addition to the general

population.

This project needs to be scheduled after the earlier or near-term projects because it requires inputs

and information from chemical-specific exposure and dose assessments. Biomarker data will be

restricted to a few analytes only (e.g., 3,5,6-trichloropridinol[TCPy] and arsenic in urine, VOCs and

metals in blood). Development or application of these models also requires information on

absorption, metabolism, and elimination of these chemicals, and data regarding the timing and routes

of exposures. Consequently, the applicability of this project will be restricted to few chemicals.

NHEXAS study design also introduces some difficulties in reconstructing exposure profiles. 

Temporal or repeated personal or microenvironmental measurements are not widely collected. 

Questionnaire and time-activity diaries also have limitations in providing high-level time-resolved

information on source use (e.g., pesticide applications), activities, and concentrations. Estimation of

individual dose and biomarker concentrations could be limited if sufficient temporal or spatial

information on concentrations or exposure factors are not available or need to be estimated. 

4.6 DATA ANALYSIS AREA SIX: DESIGNING EXPOSURE STUDIES

4.6.1 Overview

A major objective of the NHEXAS studies was to evaluate the feasibility of NHEXAS

concepts, methods, and approaches for the design and conduct of future population-based exposure
53

studies. To this end, ORD encouraged creative thought in both design and implementation of the

NHEXAS pilot studies. Although each study had the same basic goal of measuring multimedia,

multipathway exposures for defined populations, each employed different approaches to many of the

design, sampling, and evaluation procedures. Components, such as the hypotheses tested, selection

criteria of participants, incentives for participation, and sampling designs, differed among studies. In

some cases, state-of-the-art field measurement approaches were employed, whereas, in others, new

and novel approaches were tested. Coupled with other aspects of the studies that were common,

such as the NHEXAS questionnaire, food, water, and biological analyses, and comparative quality

assurance, the contrasting approaches provide a lucrative database for evaluation and comparisons

among the studies. The lessons learned from these evaluations and comparisons of the NHEXAS

studies will advance the state-of-the-science for future residential-based, multimedia, multipathway

exposure studies and will serve as an important first step in the design of future large- or nationalscale exposure studies based on the NHEXAS concept.

Future large-scale exposure studies must be done smarter and more efficiently. Fundamental in

attaining this goal is the use of cost-effective approaches that will provide sufficiently accurate

measures of exposure and the data needed for improving exposure models. The cost-benefit of the

various approaches used within the three studies can be evaluated to determine which procedures

worked well and where improvements are required. For example, an evaluation of the effectiveness

of the questionnaires and simplified or indirect sampling schemes may identify screening tools that can

classify more highly exposed individuals at reduced costs. Evaluations among the NHEXAS studies

of study design components, such as communication strategies and quality assurance and data

management procedures, will determine the optimum set of criteria and recommendations for

standardization in future studies.

4.6.2 Developing Priorities for the Projects 

This data analysis area (Table 10) has the single goal of using the NHEXAS experience to

improve the design of future exposure studies, a specific recommendation of IHEC. With multiple

large and small-scale exposure studies currently in their early planning phase, each of the projects

identified is critical and urgently needed to meet the goal of this data analysis area, dictating that all
54

projects need to be conducted in the near term. Therefore, the “Timing” criteria alone can not

distinguish projects for the purpose of sorting them; all projects are designated as near term. 

However, as the success of the design of an exposure study depends on a certain sequence of events,

so does the timing of certain projects within this data analysis area. Projects DES-01 and DES-02

are fundamental in planning the design of future large-scale exposure studies, and clearly need to be

started first, irrespective of other ranking criteria.
55

TABLE 10. DESIGNING EXPOSURE STUDIESa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

DES-01 Survey and Statistical Aspects of the

Design of an Exposure Field Study: 

Lessons Learned from the NHEXAS

Pilot Studies

N H H Y

DES-02 Evaluating Modeling Considerations for

the Design of Future Exposure Field

Studies

N M H Y

DES-03 Scaling Up: Evaluation of the NHEXAS

Pilot Fixed Costs, Coordination and

Communication Strategies, and Degree

of Standardization

N H H

DES-04 Influence of Incentives, Response

Rates, and Nonresponse Bias on Survey

Design

N H M

DES-05 Cost-Effectiveness of Exposure

Measures and Comparisons to Indirect

Methods

N M H Y

DES-06 Optimizing NHEXAS Pilot Information

and Methods to Move to a NationalScale Exposure Field Study

N M H

DES-07 Cross-Studies Evaluation and

Recommendations for Standardization of

Data Management Procedures in

Large-Scale Exposure Field Studies

N M M

DES-08 Evaluation of NHEXAS Results To

Derive an Optimal Set of QA/QC

Activities for Human Exposure Field

Studies

N M M

aN = near term; I = intermediate term; H = high; M = medium; L = low; Y = yes.

Both of these projects are urgently needed because they provide critical information to begin the

design process of a population-based exposure field study. A few of the projects (e.g., Project

DES-03) will compare various procedures used in the NHEXAS studies and depend on feedback of

lessons learned from those involved in conducting the studies. These projects need to be initiated

while there is still historical knowledge and availability of personnel. One such project, which will
56

document important lessons learned from those conducting field monitoring and laboratory analyses,

has been initiated (Appendix C). 

Fortunately, all design-related comparisons among the three NHEXAS studies are not

dependent on the availability of a complete NHEXAS database and are more feasible in the near

term (Projects DES-3 and DES-4). Still other critical projects require results-oriented comparisons

and are dependent on availability of both media concentrations and identifying information, as well as

on preliminary analysis of the NHEXAS database descriptive statistics. These projects are judged

somewhat less feasible in the near term because of fundamental differences in the NHEXAS study

designs, but it is equally important that these projects be initiated as soon as practical to provide

critical components for future design processes.

The required sequence for conducting the projects in the Designing Exposure Studies data

analysis area, along with other applicable prioritizing criteria for each project, is summarized in Table

10. Specific comments and rationale for near-term sequencing are provided below for each project. 

DES-01 Survey and Statistical Aspects of the Design of an Exposure Field Study: Lessons

Learned from the NHEXAS Pilot Studies — The goal of this project is to provide

directly relevant and specific guidance for the sample and survey design aspects of future

large-scale, multichemical, multimedia exposure field studies. A review, revision, and

updating of the discussions, analyses, and conclusions that provided the foundation for the

NHEXAS design, as presented in the Callahan et al. paper (JEAEE, 1995), will be

conducted in light of the NHEXAS studies experience. The hypothetical calculations

would be replaced with calculations based on actual NHEXAS studies data. In addition,

the analytical and statistical hypotheses that were generated in the design of the NHEXAS

pilot studies will be reviewed to determine which hypotheses were testable and which

were not.

This is the first of two projects identified that provides foundational information and should be

conducted before future exposure study design processes are initiated. Fundamental in the design

process is the selection of the appropriate survey and sample designs (sampling units, households,

screening strategies, household members, etc.) that will support the hypotheses to be tested. The
57

NHEXAS studies provide the information needed so that hypothetical interclass correlations, design

effects, and variances now can be replaced with actual data for different pollutants and classes of

pollutants. The project is highly feasible and should commence with the availability of the NHEXAS

database. It has broad applicability for exposure studies in general and is urgently needed for the

design of currently planned ORD national-scale exposure studies.

DES-02 Evaluating Modeling Considerations for the Design of Future Exposure Field

Studies — The goal of this project is to establish a procedure wherein modeling

considerations are accommodated in the early stages of the design of future exposure field

studies. In conducting field studies, usually a study is designed, monitoring data and other

related data are gathered, and then statistical analyses are performed to interpret the data. 

However, from a model development, model application, or model evaluation perspective,

the data gathered may be insufficient, particularly for inferential purposes, if information on

important exposure model variables have not been obtained during the study. To achieve

the goal of this project, the model parameters for incorporation into the study design must

be understood at the earliest stages of study planning. Sample parameters include those

related to time/activity patterns, contact rates, and dermal and dietary exposure (e.g.,

surface coverings in residences, contact times with these surfaces).

This is the second project identified that is sequentially required in the near term , and that provides

critical input to begin the design process of an exposure study. Exposure measurement studies alone

cannot provide all the information required in the risk assessment/risk management paradigm used by

EPA. Models are required to interpret measurement results and select actions to protect the public. 

It is critical that exposure studies provide the correct information for exposure modeling, and that this

information is considered from the very inception of the design process. This project is equally

applicable and as urgently needed as the higher ranked project, but it is judged somewhat less

feasible because of the pilot nature of NHEXAS studies and the need for more complete evaluation

of the most effective procedures and methodologies employed in each of the studies.
58

DES-03 Scaling Up: Evaluation of the NHEXAS Pilot Fixed Costs, Coordination and

Communication Strategies, and Degree of Standardization — The goal of this project

is to compare and contrast the implementation and communication strategies of the three

consortia to determine which worked well and which components need improvement and

standardization for the most cost-efficient exposure field study possible. This project

evaluates the NHEXAS pilot start-up expenditures and cost implications for various scales

of coverage, the effectiveness of coordination approaches that were used and their

application to a full scale survey, and communication approaches as results were shared

with respondents and with local, state, and federal officials and organizations. A key

component of the analysis will be the evaluation of approaches that were standardized

explicitly and a determination of whether or not the degree of standardization was

adequate. 

This is a highly feasible project that must be initiated immediately before opportunities for feedback

from the consortia and cooperating agencies involved in conducting the NHEXAS field studies are

lost. Experiences gained from coordinating and implementing the pilot studies provide valuable

information for the design of future studies. Cost of implementation and standardization of various

components can be compared among studies to provide a relative basis for scale-up. 

Communications strategies are an important aspect of the success of an exposure field study, and the

three studies provide the opportunity to optimize approaches. All information is currently available

and not dependent on the combined NHEXAS database, making this project highly feasible for

immediate initiation. Applicability is high because the over-arching goal of all future field studies is

cost-effectiveness. 

DES-04 Influence of Incentives, Response Rates, and Nonresponse Bias on Survey Design —

The goal of this project is to analyze NHEXAS recruitment procedures and incentives and

their effects on response rates for various subpopulations. Analysis will be conducted of

potential bias resulting from NHEXAS nonresponse based on information obtained from

the descriptive questionnaire, and information and observations recorded by interviewers
59

on noncontacts or nonrespondents for each study and for various subpopulations,

important elements in the design of future exposure studies. 

This project will investigate other critical elements for the design of a successful field study. This

project is highly feasible and is also not dependent on the availability of the combined NHEXAS

database. It can be initiated immediately. Applicability is ranked as medium because the NHEXAS

pilot studies cannot provide information on the procedures and approaches not specifically

incorporated in them. 

DES-05 Cost-Effectiveness of Exposure Measures and Comparisons to Indirect Methods —

The goal of this project is to evaluate the cost-effectiveness of exposure measures for

pollutants and pathways using decision analysis, value of information, and cost-benefit

analysis techniques. Data from NHEXAS pilot studies questionnaires, environmental

sampling, personal sampling, and biomarkers will be analyzed to assess the reproducibility,

accuracy, limits of detection, ranges, interferences, uncertainty, and costs, for the purpose

of evaluating direct measures relative to indirect methods that use existing data and

models. From the analysis, methods that were unsuccessful and other methods (i.e.,

questionnaires, simplified or indirect sampling schemes) that could serve as screening tools

in large-scale exposure studies to classify more highly exposed individuals and reduce

costs will be identified. 

As with each project in this analysis area, this project is desirable in the near term to provide

important information for a specific component of the exposure study design process. This project is

broadly applicable to all exposure field studies to meet the goal of better information at reduced cost. 

For this reason, it is very much in demand for exposure studies that are entering the planning phase in

the near future, including a potential national-scale NHEXAS and a longitudinal birth cohort study. 

This project is ranked moderately feasible because the NHEXAS studies provide only limited

instances where comparisons are possible between direct measures and indirect methods.

DES-06 Optimizing NHEXAS Pilot Information and Methods To Move to a National-Scale

Exposure Field Study — The goal of this project is to provide a defensible scientific basis
60

to design and implement national-scale exposure field studies. The information obtained in

the pilot studies and other source and effects information will be utilized to prioritize the

selection of pollutants and pathways leading to exposure. Included would be an evaluation

of the ability of each consortium to achieve the objectives or hypotheses originally

proposed for each type of investigation. A thorough evaluation of single- and multimedia

pollutant issues and regulatory initiatives for the purpose of designing a large-scale

exposure study will be performed. 

This project will capture and integrate the knowledge gleaned from the analysis, interpretation, and

evaluation of the experiences in undertaking the NHEXAS pilot studies for assisting in designing and

planning the next generation of large-scale exposure field studies. The products of this project will

provide input for developing hypotheses based on priority pollutants and pathways. This project

specifically addresses large-scale studies, although the concepts and determinants are equally

applicable to any exposure field study. The project is feasible using data from both the NHEXAS

studies and other sources, but depends heavily on the results of other elements of the strategic

analysis plan.

DES-07 Cross-Study Evaluation and Recommendations for Standardization of Data

Management Procedures in Large- Scale Exposure Field Studies — The goal of this

project is to analyze the data collection and automated survey management procedures

developed for each NHEXAS pilot study from sampling, through sample analysis and to

inclusion in the final database. The data QA/QC procedures and QC data will be

evaluated, and the resulting database structures will be examined. The strengths and

weaknesses of the three approaches will be noted with respect to ongoing EPA data

management initiatives. NHEXAS pilot QC data will be analyzed, and recommendations

for future studies will be developed. These recommendations will include areas that would

benefit from standardization; for example, data transfer from analytical laboratories,

database elements, QA/QC codes, information shells, etc.

This, and the last project (Project DES-08) in this data analysis area, address two design components

that have received inadequate consideration during the design processes of previous exposure
61

studies. Consequently, insufficient planning and budgeting of resources have resulted in abbreviated

QA programs and databases. This project is feasible in the near term using the results and

comparisons of the approaches used in the NHEXAS studies. This project, completed in a timely

manner, will provide valuable information to more effectively complete the design and budgeting

processes to create quality databases for planned and future large-scale exposure studies. 

DES-08 Evaluation of NHEXAS Results To Derive an Optimal Set of QA/QC Activities for

Human Exposure Field Studies — The goal of this project is to identify and evaluate the

QA/QC programs implemented across laboratories and consortia in the NHEXAS

studies. This will include an analysis of the across-studies QC program conducted by

NIST and the EPA comparability study data. The project will develop an annotated

inventory of recommended QA/QC activities needed to successfully conduct large-scale

human exposure measurement studies. This will include all phases of the study, from

planning to final database development. 

A near term analysis of NHEXAS data applicable to this critical component of study design will

provide guidance for use in a large-scale study design to assure that the study produces data of

appropriate quality, while keeping cost to a minimum. The successes and benefits of various study

activities can be evaluated. Feasibility is judged as moderate because the QA/QC programs within

and among the NHEXAS studies were not uniformly applied, nor did they necessarily cover all

aspects of the studies from data objectives through sample collection, analysis, and reporting. The

resulting recommendations would have some applicability to any exposure field studies.
A-1

APPENDIX A

List of Workshop Participants

John Adgate, Ph.D

University of Minnesota

Box 807 6MHC

420 Delaware Street, SE

Minneapolis, MN 55455

Gerald Akland

Research Triangle Institute

P.O. Box 12194

3040 Cornwallis Road

Research Triangle Park, NC 27709-2194

Maurice Berry, Ph.D

U.S. EPA/NERL

U.S. EPA (MS-564)

26 W Martin Luther King Boulevard

Cincinnati, OH 45268

Robert Buck, Ph.D

Western Michigan University

Department of Mathematics and Statistics

Kalamazoo, MI 49008

Timothy Buckley, Ph.D

Department of Environmental Health and

 Sciences

Johns Hopkins University, Room 6010

615 N. Wolfe Street

Baltimore, MD 21205

Laureen Burton, M.P.H.

U.S. EPA

401 M Street, SW

Mail Code 66045

Washington, DC 20460

David Camann

Southwest Research Institute

P.O. Drawer 28510

San Antonio, TX 78228

Andy Clayton

Research Triangle Institute

3040 Cornwallis Road

P.O. Box 12194

Research Triangle Park, NC 27709-2194

Robert Clickner, Ph.D.

Westat, Inc.

1650 Research Boulevard

Room RP4012

Rockville, MD 20850

Yoram Cohen, Ph.D.

UCLA

Department of Chemical Engineering

5531 Boelter Hall

Los Angeles, CA 90095-1592

Steve Colome, Sc.D.

UCLA

5319 University Drive, No. 430

Irvine, CA 92612

Larry Cupitt, Ph.D.

U.S. EPA/ORD/NERL (MD-77)

79 Alexander Drive

Research Triangle Park, NC 27711

Michael Dellarco, Ph.D.

U.S. EPA/NCEA-W

401 M Street, SW

Washington, DC 20460

Julie Du, Ph.D.

U.S. EPA
A-2

401 M Street, SW

Washington, DC 20460 Ying Feng, Ph.D.

Ohio Department of Health

Bureau of Environmental Health and 

 Toxicology

246 N. High Street

Columbus, OH 43215-2412

Kenneth Fisher, Ph.D.

ODPHP/DHHS

738-G Humphrey Bldg.

200 Independence Avenue, SW

Washington, DC 20201

Natalie Freeman, Ph.D.

EOSHI-RWJMS

170 Frelinghuysen Road

Piscataway, NJ 08854

Panos Georgopoulus, Ph.D.

EOHSI-RWJMS

170 Frelinghuysen Road

Piscataway, NJ 08854

Melissa Gonzales, Ph.D.

U.S. EPA/NHEERL (MD-58A)

Research Triangle Park, NC 27711

Syd Gordon, Ph.D.

Battelle Columbus Laboratories

505 King Avenue

Columbus, OH 43201-2693

Judith Graham, Ph.D.

U.S. EPA/NERL (MD-75)

Research Triangle Park, NC 27711

Zhishi Guo, Ph.D.

U.S. EPA/NRMRL (MD-54)

Research Triangle Park, NC 27711

Karen Hammerstrom

U.S. EPA
A-3

MC 8601D

401 M Street, SW

Washington, DC 20460

Mike Herman

U.S. EPA/ORD/NERL (MD-56)

ERC Annex, 79 Alexander Drive

Research Triangle Park, NC 27709

Jane Hoppin, Sc.D.

NIEHS

P.O. Box 12233

Research Triangle Park, NC 27709

Matti Jantuneu, Ph.D.

KTL - Environmental Hygiene

P.O. Box 95

Neulaniemeutie 4

Kupio,

Finland

Lora Johnson

U.S. EPA (MD-587)

26 W. Martin Luther King Drive

Cincinnati, OH 45268

Elizabeth Julian, Ph.D.

Novigen Sciences, Inc.

1730 Rhode Island Avenue, NW

Washington, DC 20036

Freja Kamel, Ph.D., MPH

NIEHS/Epidemiology

P.O. Box 12233

Research Triangle Park, NC 27709

Wendy Kaye, Ph.D.

Agency for Toxic Substances and Disease

 Registry

1600 Clifton Road, NE, Mail Stop E-31

Atlanta, GA 30333

Patrick Kennedy

U.S. EPA 

401 M Street, SW

Washington, DC 20460
A-4

Pat Kinney, Ph.D.

Columbia University

School of Public Health

600 Haven, B-1

New York, NY 10032

Steve Knott

U.S. EPA

401 M Street, SW

Washington, DC 20460

Ann Kukowski

Minnesota Dept. of Health

121 E. 7th Place

St. Paul, MN 55164

Jack Leiss

Analytical Sciences, Inc.

2605 Meridian Parkway

Suite 200

Durham, NC 27712

Kelly Leovic

U.S. EPA/NERL (MD-56)

Research Triangle Park, NC 27711

Paul Lioy, Ph.D.

EOHSI - UMDNJ

170 Frelinghuysen Street

Piscataway, NJ 08855

David MacIntosh, Sc.D.

University of Georgia

206 Environmental Health Building

Athens, GA 30602-2102

Randy Maddalena, Ph.D.

Lawrence Berkeley National Labs

1 Cyclotron Road

MD-90-3058

Berkeley, CA 94720

Scott Masten, Ph.D.

NIEHS

111 T.W. Alexander Drive

Research Triangle Park, NC 27709

Suzanne McMaster

U.S. EPA/NHEERL (MD-51A)

Research Triangle Park, NC 27711

Lisa Melnyk, Ph.D.

U.S. EPA/NERL (C1)

26 W. Martin Luther King Drive

Cincinnati, OH 45268

Deirdre Murphy, Ph.D.

U.S. EPA/OAR/OAQPS (MD-13)

Research Triangle Park, NC 27711

Larry Needham, Ph.D.

Centers for Disease Control and Prevention

NCEH/EHL (Mail Stop F17)

4770 Buford Highway, NE

Atlanta, GA 30341-3724

Miles Okino, Ph.D.

U.S. EPA

P.O. Box 93478

Las Vegas, NV 89193-3478

Will Ollison, Ph.D.

American Petroleum Institute

1220 L. Street, NW

Washington, DC 20005

Mary Kay O’Rouke, Ph.D.

University of Arizona

EOH, Box 210468

1435 N Fremont Avenue

Tucson, AZ 85721

Haluk Ozkaynak, Ph.D.

U.S. EPA/NERL (MD-56)

Research Triangle Park, NC 27711
A-5

Mulihan Pandian

2920 North Green Valley

Suite 524

Henderson, NV 89014

Edo Pellizzari, Ph.D.

Research Triangle Institute

P.O. Box 12194

Research Triangle Park, NC 27709-2194

Paul Price

129 Oakhurst Road

Cape Elizabeth, ME 04107

James J. Quackenboss

U.S. EPA/NERL

P.O. Box 93478

Las Vegas, NV 89193-3478

Gary Robertson

U.S. EPA/NERL

P.O. Box 93478

Las Vegas, NV 89193

Seumas Rogan

University of Arizona

EOH, Box 210468

1435 North Fremont Avenue

Tucson, AZ 85719

Barry Ryan, Ph.D.

Department of Environmental and

 Occupational Health

Rollins School of Public Health

Emory University

1518 Clifton Road, NE

Atlanta, GA 30322

Christopher Saint, Ph.D.

U.S. EPA

401 M Street, SW

Washington, DC 20460

Susan Schober, Ph.D.

CDC/National Center for Health Statistics

6525 Belcrest Road, Room 1000

Hyattsville, MD 20782
A-6

Judy Schreiber, Ph.D.

New York State Dept. of Health

547 River Street

Flanigan Square, Room 330

Troy, NY 12180-2216

Keith Schwer

UNLV, Center for Business and Economic

Research

4505 Maryland Parkway

P.O. Box 456002

Las Vegas, NV 89154-6002

Les Sparks, Ph.D.

U.S. EPA/NRMRL (MD-54)

Research Triangle Park, NC 27711

Chuck Stroebel

Minnesota Department of Health

121 East Seventh Place

Suite 220

St. Paul, MN 55164

Helen Suh, Sc.D

Harvard School of Public Health

235 Lincoln Street

Newton, MA 02461

Keven Teichman

U.S. EPA/OSP

401 M Street, SW (8104R)

Washington, DC 

Kent Thomas

U.S. EPA/NERL (MD-56)

79 T.W. Alexander Drive

Research Triangle Park, NC 27711

Nga Tran, Ph.D., CIH

Johns Hopkins University

School of Hygiene and Public Health

624 N. Boardway

Baltimore, MD 21205
A-7

Gene Tucker, Ph.D.

U.S. EPA/NRMRL

Research Triangle Park, NC 27711

Edward Washburn

U.S. EPA/ORD/OSP

401 M Street, SW (8104R)

Washington, DC 20460

Roy Whitmore, Ph.D.

Research Triangle Institute

P.O. 12194

3040 Cornwallis Road, Cox Building

Research Triangle Park, NC 27709-2194

Harvey Zelon

Research Triangle Institute

P.O. Box 12194

Research Triangle Park, 27709

Maria Zufall, Ph.D. 

U.S. EPA/NERL (MD-56)

Research Triangle Park, NC 27711

Periann Wood, Ph.D.

U.S. EPA/NHEERL (MD-66)

Research Triangle Park, NC 27711

Bob Krieger

Personal Chemical Exposure Program

University of California

Department of Entomology

Riverside, CA 92521

Chuck Steen, Ph.D.

U.S. EPA/NERL (MD-75)

Research Triangle Park, NC 27711
B-1

APPENDIX B

Science Advisory Board Reviewers

U.S. Environmental Protection Agency

Science Advisory Board

Integrated Human Exposure Committee

National Human Exposure Assessment Survey Advisory Panel

July 10-11, 2000

CHAIR

Dr. Henry A. Anderson, Chief Medical Officer, Wisconsin Bureau of Public Health,

Madison, WI

MEMBERS

Dr. Annette Guiseppi-Elie, Senior Consultant, Dupont Spruance Plant, Richmond, VA

Dr. Michael Jayjock, Senior Research Fellow, Rohm and Haas Co., Spring House, PA

Dr. Kai-Shen Liu, California Department of Health Services, Berkely, CA

Dr. Thomas E. McKone, School of Public Health, University of California, Berkely, CA

Dr. Jerome O. Nriagu, The University of Michigan, School of Public Health, Department of

Environmental and Industrial Health, Ann Arbor, MI

Dr. Barbara Petersen, Novigen Sciences, Inc., Washington, DC

Dr. David Wallinga, Institute for Agriculture and Trade Policy, Minneapolis, MN

Dr. Charles Wechsler, Telcordia Technologies, Red Bank, NJ

CONSULTANTS

Dr. Leyla McCurdy, Director, Indoor Air Programs, American Lung Association,

Washington, DC

Dr. Maria Morandi, University of Texas Health Science Center at Houston, School of Public

Health, Houston, TX

SCIENCE ADVISORY BOARD STAFF

Mr. Samuel Rondberg, Designated Federal Officer, U.S. Environmental Protection Agency,

Science Advisory Board (1400A), Washington, DC
B-2

Ms. Wanda R. Fields, Management Assistant, U.S. Environmental Protection Agency,

Science Advisory Board (1400A), Washington, DC
C-1

APPENDIX C

NHEXAS Projects and Analyses—Completed and In Progress
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Development of NHEXAS Databases

The NERL plans to make the databases from the NHEXAS pilot studies available to the

scientific community both within and outside of EPA. The NHEXAS pilot study results, metadata,

and documents will be available on the Internet by the fall of 2001. The actual data will be stored

and maintained in ORACLE databases on an EPA server. Metadata for the data and documents,

available through EPA’s Environmental Information Management System (EIMS), will be linked to

the actual data sets and documents. This will allow users browse the data and document files and to

select the sample types, analyte classes, or questionnaires that they want to download to their own

system. The database design and contents were peer reviewed in the summer of 2000.

Database Organization. There will be three types of data sets for each study: questionnaires,

analytical results, and QA/QC results data. Each set will include household and individual identifiers

(without personal information to identify the specific person), as well as information for applying

survey weights. In addition, data dictionary and code files will be included to document the contents

of the results data. Their description follows.

(1) Questionnaire Data Sets. The data from each questionnaire will be provided as a separate data

set. Questionnaire data evaluate the demographics, housing characteristics, lifestyle, activity

patterns, and health of the participants. Data from all questions in a questionnaire will be

included in the data set, except for sensitive data. Examples of sensitive information include:

name, address, date of birth, and phone number. The following questionnaire data will be

available, depending on what was collected in a particular NHEXAS study:

•Baseline

•Descriptive

•Follow up

•Food Diary or Dietary Checklist

•Food Diary Follow up

•Technician Walk-Through

•Time Diary and Activity

The codes for the questionnaire responses will be defined in code files, which are identified in the data

dictionary corresponding to each file. 

(2) Analytical Results Data Sets. This large complex set of data from three studies covers many

types of samples. Analytical data are derived from samples of yard soil, house dust, personal,

indoor, and outdoor air, drinking water, food and beverages, dermal wipes, blood, and urine. 

The analytical result data will be available to the user in subsets which are defined by the sample

type and the analyte class. Sample types will be defined for each study based on the sampling

medium, location, and collection methods used. Each row of these data sets will provide the

results for the analytes of one sample obtained from a given analytical or determinative method. 

The row will include identifying and sample information (e.g., dates, units), statistical/survey

information (i.e., sample weight and strata), and codes to identify the adequacy of the sample

results relative to detection (or quantitation) limits or quality control checks.
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(3) QA Data Sets. One data set will be provided for each type of QA/QC sample, that is, one for 

spikes (field and laboratory), one for replicates (field, laboratory and analysis), one for blanks

(field, analytical and reagent), etc. Each row in these data sets will contain the analytical result

information for all analytes in the analyte class for one sample. 

(4) Data Dictionary Files. Each entry in a data dictionary will include information about a variable

(column) in the corresponding data set. This includes descriptive labels to define the variable,

ranges of acceptable values, units of measurement, missing values, and codes used for

categorical variables. 

(5) Code Files. A code set will be available for each column in a data set that contains values

representing discrete or categorical responses. This includes code values assigned to missing or

non-response data. Each code set will provide the link between a unique set of coded values

and their descriptions, and will be identified in the data dictionary by a unique code set name. 

Database Review. Each of the investigators are required to assess the completeness and accuracy of

the data sets provided to the EPA. However, to help ensure that the publicly available NHEXAS

databases are complete and accurate versions of the study results, additional reviews of the

databases will be conducted. These reviews include assessments of the analytical results and

questionnaire data sets, the corresponding data dictionaries and code files, and the document files

(QSIPs and protocols) to check the:

- validity and completeness of codes used in the database and the definitions provided in the data

dictionary and code files; 

- correspondence of the formats, types, and ranges of values in the database to those specified in the

data dictionary;

- labels for variables (including units of measurement where necessary);

- completeness of document files for the study design, QA plans, and protocols; and 

- consistency of summary statistics with those provided (or published) by the investigators.

Database Summaries. Summary tables of the NHEXAS databases will be developed to document

the completeness of the data sets for multimedia and multipathway exposure estimation. This includes

identifying the number of samples having valid and measurable results, and providing univariate

descriptive statistics (mean, median, percentiles) for the analytical results data by sample type and

chemical. 

Lessons Learned in the Actual Conduct of the NHEXAS Pilot Studies

Most information from the NHEXAS pilot studies will be derived from analyses of the data. 

However, the field study professionals have specialized first-hand knowledge of what worked well

and what didn’t work well in actually performing a study of this complexity and magnitude. 

Therefore, a project was developed to define the strategies, procedures, and approaches that are

likely to work well for future field studies. ORD will conduct interviews with the NHEXAS pilot

consortia members, summarize the findings, and then conduct a 1-day workshop to prioritize findings
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and develop key recommendations. Information collected will address procedures and practices,

including but not limited to the effectiveness of administering questionnaires, sampling methods,

sample handling and tracking, laboratory procedures, participant training and burden (time and level

of understanding), field staff burden, and database development. The planned products from these

activities will be a journal article summarizing the findings and report that provides guidance

recommendations on approaches for human exposure field studies. The products will be available in

early 2001.

Published Journal Articles

Region V NHEXAS Pilot Study

Whitmore, R.W., Byron, M.Z., Clayton, C.A., Thomas K.W., Zelon H.S., Pellizzari E.D.,

and Quackenboss.J.J. (1999) “Sampling Design, Response Rates and Analysis Weights for the

National Human Exposure Assessment Survey (NHEXAS) in EPA Region 5” Journal of 

Exposure Analysis and Environmental Epidemiology 9(5): 369-380.

Clayton, C.A., Pellizzari, E.D., Whitmore, R.W. Perritt, R.L. and Quackenboss, J.J. (1999)

“National Human Exposure Assessment Survey (NHEXAS): Distributions and Associations of

Lead, Arsenic and Volatile Organic Compounds in EPA Region 5” Journal of Exposure

Analysis and Environmental Epidemiology 9(5): 381-392.

Pellizzari, E.D., Fernando, R., Cramer, G.M., Meaburn, G.M., and Bangerter, K. (1999)

“Analysis of Mercury in Hair of EPA Region V Population” Journal of Exposure Analysis

and Environmental Epidemiology 9(5): 393-401.

Thomas, K.W., Pellizzari, E.D., and Berry, M.R. (1999) “Population-based Dietary Intakes

and Tap Water Concentrations for Selected Elements in the EPA Region V National Human

Exposure Assessment Survey (NHEXAS)” Journal of Exposure Analysis and

Environmental Epidemiology 9(5): 402-413.

Freeman, N.C.G., Lioy P.J. (1999) “Responses to the Region V NHEXAS Time/Activity

Diary.” Journal of Exposure Analysis and Environmental Epidemiology 9(5): 414-426.

Reed, K.J., Jimenez, M., Freeman, N.C.G., and Lioy, P. J.(1999) “Quantification of

Children’s Hand and Mouthing Activities Through a Videotaping Methodology” Journal of 

Exposure Analysis and Environmental Epidemiology 9(5): 513-520.

Edwards,R.D., and Lioy, P.J. (1999) “The EL Sampler: A Press Sampler for the Quantitative

Estimation of Dermal Exposure to Pesticides in Housedust” Journal of Exposure Analysis

and Environmental Epidemiology 9(5): 521-529.
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Quackenboss, J.J., Pellizzari, E.D., Shubat, P. Whitmore, R.W., Adgate, J.L., Thomas, K.W.,

Freeman, C.G., Stroebel, C., Lioy, P.J., Clayton, A.C., Sexton, K. (2000). “Design Strategy

for Assessing Multi-Pathway Exposure for Children: the Minnesota Children’s Pesticide

Exposure Study (MNCPES) J. Expos Anal Environ Epi 10:145-158

Baltimore NHEXAS Pilot Study:

Scanlon, K.A., MacIntosh, D.L, Hammerstrom, K.A., and Ryan, P.B. (1999) “A Longitudinal

Investigation of Solid-Food based Dietary Exposure to Selected Elements” Journal of 

Exposure Analysis and Environmental Epidemiology 9(5): 485-493.

MacIntosh, D.L., Needham, L.L., Hammerstrom, K.A., and Ryan, P.B. (1999) “A

Longitudinal Investigation of Selected Pesticide Metabolites in Urine” Journal of Exposure

Analysis and Environmental Epidemiology 9(5): 494-501.

Echols, S.L., MacIntosh, D.L., Hammerstrom, K.A. and Ryan, P.B. (1999) “Temporal

Variability of Microenvironmental Time Budgets in Maryland” Journal of Exposure Analysis

and Environmental Epidemiology 9(5): 502-512.

MacIntosh, D.L., Hammerstorm, K.A., and Ryan, P.B. (1999) “Longitudinal Exposure to

Selected Pesticides in Drinking Water” Human and Ecological Risk Assessment 5(3):575-

588.

MacIntosh, D.L., Kabiru, C., Scanlon, C.A., and Ryan, P.B. (2000) “Longitudinal investigation

of exposure to arsenic, cadmium, chromium, and lead via beverage consumption” J. Expo.

Anal. Environ. Epidem. 10(2): 196-205.

Ryan, P.B., Huet, N., MacIntosh, D.L. (2000) “Longitudinal investigation of exposure to

arsenic, cadmium, and lead in drinking water.” Environ. Health Persp. (in press)

Arizona NHEXAS Pilot Study:

Robertson, G.L., Lebowitz, M.D., O’Rourke, M.K.,Gordon, S., and Moschandreas, D.

(1999) “The National Human Exposure Assessment Survey (NHEXAS) Study in ArizonaIntroduction and Preliminary Results” Journal of Exposure Analysis and Environmental

Epidemiology 9(5): 427-434.

O’Rourke, M.K., Fernandez, L.M., Bittel, C.N., Sherrill J.L., Blackwell, T.S., and Robbins,

D.R. (1999) “Mass Data Massage: An Automated Data Processing System Used for

NHEXAS Arizona” Journal of Exposure Analysis and Environmental Epidemiology 9(5):

471-484.
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O’Rourke, M.K., Rogan, S.P., Jin, S., and Robertson, G.L. (1999) “Spatial Distributions of

Arsenic Exposure and Mining Communities from NHEXAS Arizona” Journal of Exposure

Analysis and Environmental Epidemiology 9(5): 446-455.

Gordon, S.M., Callahan, P.J., Nishioka, M.G., Brinkman, M.C., O’Rourke, M.K., Lebowitz,

M.D., and Mosschandreas, D.M. (1999) “Residential Environmental Measurements in the

National Human Exposure Assessment Survey (NHEXAS) Pilot Study in Arizona: Preliminary

Results for Pesticides and VOCs” Journal of Exposure Analysis and Environmental

Epidemiology 9(5): 456-470.

O’Rourke, M.K., Van de Water, P.K., Jin, S., Rogan, S.P., Weiss, A.D., Gordon, S.M.,

Moschandreas, D.M., and Lebowitz, M.D. (1999) “Evaluations of Primary Metals from

NHEXAS Arizona: Distributions and Preliminary Exposures” Journal of Exposure Analysis

and Environmental Epidemiology 9(5): 435-445.

Lebowitz, M.D., O’Rourke, M.K., Rogan. S., Reses, J., Van De Water, Pl, Blackwell, A.,

Moschandreas, D.J., Gordon, S., and Robertson, G. (2000) “Indoor And Outdoor PM10 And

Associated Metals and Pesticides in Arizona” Inhalation Toxicol. 12 (suppl 1): 139-144.

Manuscripts in Preparation Under Current ORD Sponsorship

Region V NHEXAS Pilot Study

•“Analysis of Dietary and Other Exposure Pathways for Metals, with Comparisons Between

Media Concentrations and Routes of Exposure”

•“Assessment of Data Quality for the EPA Region V NHEXAS Study”

•“Assessment of Data Quality for the Minnesota Children’s Pesticide Exposure Study”

•“Contribution of activity patterns to personal exposures of NHEXAS participants”

•“Relationship of residential sources and residential conditions to household contaminant levels”

•“Relationship between pesticide levels in and around the home and hand rinse measurements

from children”

•“Relationship between activity pattern data and hand rinse measurements of pesticides in

children”

Baltimore NHEXAS Pilot Study

•“Longitudinal investigation of dietary exposure to selected pesticides”

Arizona NHEXAS Pilot Study

•“Occurrence And Distribution of Residential Exposure to Chlorpyrifos and Diazinon” 
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•“On Prediction of Multi-route and Multimedia Residential Exposure to Chlorpyrifos and

Diazinon”

•“Exposure to Pesticides by Medium and Route: The 90th Percentile and Related Uncertainties”
D-1

APPENDIX D

Project Priority Listings
D-2

PROJECT PRIORITY LISTINGSa

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

Descriptive Statistics

D-01 An Analysis of Media Concentrations, Exposure,

and Biomarkers by Demographics

N H H

D-02 Univariate Statistics for Use in Exposure and Risk

Assessment

N H M Y

D-03 Impact of Censoring and Method Sensitivity and

Precision on Multimedia Exposure Distributions and

Associations

I H H

D-04 Quantify Uncertainties in NHEXAS Data and

Assess Contribution to Model Errors

I M M

D-05 Investigate National Representativeness of

NHEXAS Sampling Results by Comparing

Measurement and Exposure Results Across the

Three Regions

I L M

Predictors of Exposure and Dose

P-01 Analysis and Comparison of NHEXAS Exposure

Data to Residential Pollutant Sources,

Concentrations, and Activity Patterns

N H H Y

P-02 Compare Traditional Indirect Method of Estimating

Dietary Exposures with Duplicate Diet Data and

Compare Methodologies Utilized in NHEXAS

N M H

P-03 Identifying Predictors of Exposure I H M

P-04 Risk Factors for Biomarkers of Internal Dose:

Demographics, Questionnaire Data, Concentrations,

and Exposures 

I M H Y

P-05 Determinants of Dose Measurements (Biomarkers)

from the NHEXAS Studies

I M H

P-06 Exploratory Data Analysis Methods for Evaluating

Relationships Among Questionnaires, Exposure,

Dose, and Risk Factors

I M M

P-07 Use of NHEXAS Data To Test Assumptions About

Activity Pattern Factors and Other Exposure Factors

in EPA Risk Assessments

I L M

Spatial and Temporal Variability

ST-01 Temporal Variability in Exposure Concentrations

and Aggregate Exposure Using NHEXAS Data

N H H
D-3

PROJECT PRIORITY LISTINGSa(cont’d)

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

Spatial and Temporal Variability (cont’d)

ST-02 Use NHEXAS Dietary and Activity Pattern Data To

Develop Predictive Relationships Between Single

Day Observations and Long-Term Patterns of

Behaviors

N H M

ST-03 Characterization of the Variance Components of

NHEXAS Data to Optimize Future Designs

N Mb H

ST-04 Spatial Variability N Mb H

ST-05 Investigate Stability of Individuals in Population

Exposure Ranks Over Time

I H M

ST-06 Spatial and Temporal Variability in Multichemical

Exposure

I Mb H

ST-07 Development and Evaluation of Models for

Interpreting and Quantifying Inter- and

Intraindividual Variability in Pesticide

Exposure/Dose Using NHEXAS Data.

L M H

Aggregate Exposure, Pathway Analysis, and Cumulative Risk

AE-01 Aggregate Exposure N H H Y

AE-02 Comparison of Children’s and Adults’ Exposures to

Pesticides and Other Chemicals in the Region V,

Arizona, and Maryland Studies

N M H Y

AE-03 Construction of an Empirical

Multimedia/Multipathway Exposure Distribution

Model Including Temporal Variability Based on

NHEXAS Data

I M M

AE-04 Cumulative Risk from Exposure to NHEXAS

Chemicals

L M H

Evaluation/Refinement of Current Exposure Models and Assessments

M-01 Compare Pre-NHEXAS Model Results with

NHEXAS Measurements

N H H Y

M-02 Comparison of NHEXAS Findings with NATA

Estimates for Ambient Air Levels and Exposures for

Selected VOCs and Metals

N H/M H Y

M-03 Develop Model Parameters from Qualitative and

Quantitative NHEXAS Monitoring Data,

Questionnaires, Time/Activity, and Survey Data

N M H
D-4

PROJECT PRIORITY LISTINGSa(cont’d)

Project ID Project Title Timing Feasibility

Broad

Applicability

Demand

(Urgency)

Evaluation/Refinement of Current Exposure Models and Assessments (cont’d)

M-04 Evaluate Implications of NHEXAS Results for

Existing Chronic Exposure Assessment

Methodologies

I H/M H Y

M-05 Evaluation of Existing Multimedia Models Using the

NHEXAS Data Set

I M H

M-06 Quantify Uncertainties in NHEXAS Data and

Assess Contribution to Model Errors

I M M

M-07 Reconstruct Exposure and Dose Profiles from

Biomarker Data Utilizing Questionnaire and

Environmental Measurements

I M M

Designing Exposure Studies

DES-01 Survey and Statistical Aspects of the Design of an

Exposure Field Study: Lessons Learned from the

NHEXAS Pilot Studies

N H H Y

DES-02 Evaluating Modeling Considerations for the Design

of Future Exposure Field Studies

N M H Y

DES-03 Scaling Up: Evaluation of the NHEXAS Pilot Fixed

Costs, Coordination and Communication Strategies,

and Degree of Standardization

N H H

DES-04 Influence of Incentives, Response Rates, and

Nonresponse Bias on Survey Design

N H M

DES-05 Cost-Effectiveness of Exposure Measures and

Comparisons to Indirect Methods

N M H Y

DES-06 Optimizing NHEXAS Pilot Information and Methods

to Move to a National-Scale Exposure Field Study

N M H

DES-07 Cross-Studies Evaluation and Recommendations for

Standardization of Data Management Procedures in

Large-Scale Exposure Field Studies

N M M

DES-08 Evaluation of NHEXAS Results To Derive an

Optimal Set of QA/QC Activities for Human

Exposure Field Studies

N M M

aN = near term; I = intermediate term; H = high; M = medium; L = low; Y = yes.

bSpatial variability can be determined on national, regional, and community bases when the NHEXAS data

 sets are available. However, the exact location of NHEXAS participants will not be included in the

 NHEXAS data sets to protect the confidentially of the individual participants of the study. Thus,

 comparisons of personal exposures with point sources cannot be accomplished without the cooperation of

 the principal investigators of the various NHEXAS consortia. Therefore, the criterion of feasibility was

 ranked medium for these projects, as compared to other projects without such concerns.
E-1

APPENDIX E

Project Descriptions
E-2

DESCRIPTIVE STATISTICS PROJECT

Project Name: D-01. An Analysis of Media Concentrations, Exposure, and Biomarkers by Demographics 

Short Project

Description:

Descriptive analysis of media concentrations, exposure, and biomarker measurements for

population subgroups (age, gender, ethnicity, SES, urban/rural, or other important

groupings) for each NHEXAS study.

Goal/Objective: To provide a descriptive analysis of media concentrations and biomarker measurements by

population characteristics in order to identify susceptibility factors and differences among

groups and to compare distributions with other studies.

Significance of

Project:

(1)

Will serve as basis for planning and interpretation of NHEXAS data and to identify

subpopulations for further study.

(2)

Provides baseline information for comparison to other locations such as Superfund sites

and to assess trends.

(3)

Useful to EPA and others doing analysis of NHEXAS data and for planning further

studies

Suggested

Approach:

Statistical comparison of weighted distributions (frequency, means, etc.) by population

subgroups (from questionnaire data) for media concentrations, biomarkers, and exposure to

assess differences and similarities between or among subgroups.

Data or Input 

Needs:

Questionnaires and time/activity data from each of the studies.

Biomarker and environmental measurements data from each study.

Detection limits for environmental chemicals from each study.

Population weights and stratification variables.

Feasibility

(of analyses with

current NHEXAS

databases):

Data currently exists, questionnaires are the same across groups, comparability of analytic

results will be assessed using information about detection levels. There is concern over

the level of stratification (limited cell sizes) that can be achieved because of measurements

below detection and incomplete sampling of some media (e.g., subsampling of homes for

outdoor air measurements). 

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.1 0.1 1.0 1 1

Research Outputs

(1) Identify those chemicals for which there is adequate data for analysis; determine strata to be used in analysis

(2) Final output: Manuscript, tables, and graphs of distributions by strata and completed statistical analysis and

interpretation

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project EA-2.
E-3

DESCRIPTIVE STATISTICS PROJECT

Project Name: D-02. Univariate Statistics for Use in Exposure and Risk Assessment

Short Project

Description:

Develop univariate descriptive statistics (distributional information) for NHEXAS data

that can be used broadly in exposure and risk assessment. 

Goal/Objective: To provide risk assessors and other users with information for use in exposure and risk

assessment and in the design of human health effects studies and to compare NHEXAS

results to other existing relevant study results.

Significance of

Project:

Exposure and risk assessors use estimates of various exposure concentrations and 

“exposure factors” in their calculations of exposure and risk. These are quite often point

estimates or distributions from very limited data sets. The data collected by NHEXAS

can be used to better define distributions of these concentrations and exposure factors

(e.g., activities, time spent in specific locations, dietary intake, product use). This will

reduce the uncertainty associated with these assessments. Major users of this

information will be risk assessors in EPA, other federal agencies, industry, academia, and

state and local governments, as well as epidemiologists and other health effects

researchers who need to classify members of a cohort based on exposure.

Suggested

Approach:

Work with EPA/NCEA to identify factors and point estimates that commonly are used in

risk assessment and for which data were collected in one or more of the NHEXAS pilots. 

Develop summary statistics (including distributional information) for these data. These

analyses should include distributions for the total population and for selected

subgroups where the data will allow. These should be suitable for inclusion in EPA

guidance, such as the Exposure Factors Handbook. These analyses should identify the

appropriate caveats, limitations, and uncertainties associated with the data and resulting

statistics. The results should also compare the statistics with similar information from

other studies (e.g., NHANES, TEAM).

Data or Input Needs: The activity and concentration data collected by all NHEXAS pilot studies.

Summary descriptive statistics.

Meta-data to understand caveats.

Other data sets (e.g., NHANES, TEAM, Exposure Factors Handbook).

Feasibility

(of analyses with

current NHEXAS

databases):

This is highly feasible with NHEXAS data. Each consortium will be developing

summary statistics for its data. It should be feasible to identify factors for inclusion in

EPA guidance.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.5 0.5 1.0 1 1

Research Outputs

(1) Provide statistics to EPA, including descriptions of the data and its limitations for use in risk assessment

(2) Final Output: Revision of EPA Exposure Factors Handbook

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project A-2.
E-4

DESCRIPTIVE STATISTICS PROJECT

Project Name: D-03. Impact of Censoring and Method Sensitivity and Precision on Multimedia Exposure

Distributions and Associations

Short Project

Description:

This study will examine how method sensitivity and precision, and the censoring of data

below detection limits, affect the estimation of distributions and means for exposure, media

concentration, and biomarker measurements; and the evaluation of associations among

such measurements. To the extent possible, intakes will be used in order to make the

assessment on a total exposure basis.

Goal/Objective: To investigate the degree to which the NHEXAS goal of measuring total exposure may be

limited by the method precision, sensitivity, and censoring of data below DLs.

Significance of

Project:

A major goal of NHEXAS was to estimate exposure through multiple routes, especially for

those most highly exposed. This goal may be limited by the proportion of measurements

that are below DLs for some target analytes and media and because method sensitivities

differed across both media and studies. This project will be valuable in determining

methods and approaches for conducting future NHEXAS or other multimedia human

exposure studies.

Suggested

Approach:

(1) Determine the percent of measurements above DLs, and the

availability of health thresholds and QC data in order to focus the

study on the most relevant media and chemicals.

(2) Use uncensored results where available and impose censoring on

them (i.e., set values <DL to missing or to some predefined value);

compare distributions for the uncensored and censored cases. 

(3) Use QC (duplicates) data to estimate measurement error variability;

generate simulated data that one would expect using another

method with more or less precision; summarize/compare the

distributions.

(4) To the extent possible, evaluate the impacts of steps 2 and 3 both

in terms of intakes and of total exposure. 

(5) Investigate ways of assigning values to measurements that are

below DLs.

Data or Input Needs: Physical measurements from all three studies. (Summaries of distributions and DLs may be

used to conduct simulations for intake estimates and for evaluating uncertainties

associated with measurements <DLs.)

QC data.

Feasibility

(of analyses with

current NHEXAS

databases):

Will be practical and relevant only for some types of measurements (i.e., those with more

complete collection of exposures or environmental media for multiple pathways). The

selection of measurement and analysis methods for NHEXAS were based on quantifying

exposures at the “high-end” of the distribution, which may limit the availability of

measurements above detection limits for all media. 
E-5

DESCRIPTIVE STATISTICS PROJECT D-03

(cont’d)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.2 0 0.7 3 (Reg V, MD, AZ) 0.5

Research Outputs

(1) Evaluate scope/relevance of project with respect health thresholds, availability of data, degree of nondetects,

etc.

(2) Perform analyses and simulations and prepare draft manuscript

(3) Final output: Complete final manuscript

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project EA-7.
E-6

DESCRIPTIVE STATISTICS PROJECT

Project Name: D-04. Quantify Uncertainties in NHEXAS Data and Assess Contribution to Model

Errors

Short Project

Description:

Provide uncertainty estimates within the NHEXAS database that are available to

researchers and the public, so that uncertainty is addressed consistently and does not

lead to redundant effort by modelers. Identify how the data uncertainties may impact

modeling uncertainties and illustrate with case studies.

Goal/Objective: • Provide consistent, understandable uncertainty estimates of the NHEXAS data within

the NHEXAS database

• Provide guidance/advice on applicability and use of various types of data in models to

minimize inappropriate model construction.

Significance of

Project:

The NHEXAS database will be used by many researchers and the public. Inclusion of

uncertainty estimates/descriptions will avoid duplication of effort in calculating these

values, will mean that the data uncertainties are treated consistently, and will alert the

public and regulatory community of possible limitations in the use of the data.

Suggested

Approach:

Analytical Measurements

(1) Ensure that NHEXAS data are QA’d and flagged appropriately.

(2) Ensure that NHEXAS data include Limit of Detection information.

(3) Calculate standard errors for each analytical methodology (including sampling and

analysis).

(4) Tag uncertainty data to all NHEXAS data entries and provide a methodology for

error estimation with the public database.

Survey and Time/Activity Information

(1) Provide qualitative assessments of data and their applicability for modeling by

including meta data from field staff on reliability of individual household;

include expert panel judgment of uncertainties of the methodology in general,

including effects of sample size, inaccuracies of recall diaries, observer effects, time

resolution effects, etc.; and

compare survey results from NHEXAS with other data sources.

(2) Include qualitative assessments in database.

Assessment of Model Uncertainties

Convene workshop of modelers to evaluate impacts of uncertainties for variety of

analytes, with differing critical routes of exposure. Provide qualitative descriptions of

uncertainties and caveats for inclusion in the database. Provide case studies to illustrate

how errors impact modeling uncertainties.

Data or Input

Needs:

Paced by the availability of the database, the NHEXAS data need to be quality assured

to flag/remove inappropriate data. Duplicate sample data, split sample data, blanks, and

other QA/QC information on the analytical measurements need to be included in the

database. A description of the sampling and analytical methods also must be included.

Feasibility

(of analyses with

current NHEXAS

databases):

The first part of the effort is quite doable, and should build on normal QA/QC

procedures. This work is to insure that the synopsized uncertainty data also are made

readily available for researchers and the public. The impact on modeling errors is much

more likely to be case dependent, varying with each analyte and model used.
E-7

DESCRIPTIVE STATISTICS PROJECT D-04

(cont’d)

Research Outputs

(1) Review NHEXAS databases now under development for data to be included and make sure that QA/QC

data and metadata on QC are in database for both analytical and survey data

(2) NHEXAS database becomes available

(3) Calculate synopsis information from data sets now scheduled to be delivered in FY01

(4) Convene workshop or expert panel to provide qualitative description of uncertainties associated with

survey information

(5) Convene workshop or expert panel to evaluate impact of uncertainties of modeling–prepare case studies for

specific analytes/major routes of exposure

(6) Final output: Incorporate uncertainty estimates and case studies into public database

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-4.
E-8

DESCRIPTIVE STATISTICS PROJECT

Project Name: D-05. Investigate National Representativeness of NHEXAS Sampling Results by

Comparing Measurement and Exposure Results Across the Three Regions

Short Project

Description:

Very few national studies are available for use in development of national exposure

distributions; therefore, local or regional studies are used instead. The question then is

raised about the effect of using this restricted information on national exposure

estimates. The three NHEXAS studies provide a method for comparing very similar

studies to determine the magnitude of regional differences for various exposure factors.

Goal/Objective: To determine bias in estimates of national exposure factors and distributions by use of

local or regional sampling represented by NHEXAS pilot studies.

Significance of

Project:

The information provided by this project also will advance knowledge of uncertainty in

model parameters used in a variety of exposure models. The information also will help to

ascertain the geographic scale at which variables may be collected in future studies.

Suggested

Approach:

Examination of sample population distributions for various measurements collected in all

three studies. Examination should be based on current methodologies as much as

possible to facilitate quick turnaround. Appropriate analysis methods used to

determine “similarity” among studies and quantification of uncertainty should be based

on methods that provide simple, robust measures as feasible.

Data or Input

Needs:

NHEXAS data from all three studies.

Feasibility

(of analyses with

current NHEXAS

databases):

Study should be feasible. Possible difficulties may arise for some variables where

collection methods differ among studies.

Research Outputs

(1) Develop/assess framework for comparing study measurements

(2) Implement automation of comparisons

(3) Run analyses for selected variables

(4) Final output: Report on regional differences among studies, suggested values for use in national exposure

models, and values of uncertainty.

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-12.
E-9

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-01. Analysis and Comparison of NHEXAS Exposure Data to Residential Pollutant

Sources, Concentrations, and Activity Patterns 

Short Project

Description:

Analysis of questionnaire, time/activity, environmental, and exposure data collected in

the NHEXAS studies to determine the associations among measured exposures and

pollutant sources, housing characteristics, residential concentrations (e.g.,

indoor/outdoor air), and human activities (e.g., the relationship between the use of

cleaning supplies and VOC exposures; the characterization of residential dust and soil

measurements; and the relationship to personal exposure monitoring). 

Goal/Objective: To evaluate and identify hypotheses about those residential pollutant sources, housing

characteristics, residential concentrations (indoor and outdoor), and activity patterns

that contribute to human exposures, especially for high-end exposures. To determine

the value of questionnaires for understanding various aspects of exposure, and the

reliability and validity of the instruments used for ascertaining these factors. 

Significance of

Project:

To provide policymakers with information to develop guidance for reducing exposures

by both modifying pollutant sources and housing characteristics and educating the

public about how their activities contribute to exposure. Information on the relationship

between indoor/outdoor concentrations and personal exposures will be used to test

assumptions about exposure levels based on fixed monitors. In addition, the relative

value of questionnaires and diaries for understanding public health and exposure, as

well as the item-by-item value of asking each question, will be determined with the

overall goal of minimizing participant burden and costs. Identification of associations

with questionnaire information also is useful for classification of exposures in

epidemiological studies.

Suggested

Approach:

(1) For each of the NHEXAS pilots, perform pollutant-by-pollutant analyses of the

associations among residential pollutant sources, concentrations, and exposures;

housing characteristics, concentrations, and exposures; concentration

measurements in different media; and human activities, concentrations, and

exposures. For air concentrations, develop distributions of indoor/outdoor

concentration ratios. Subdivide analyses via spatial/source considerations (e.g.,

urban/rural, smoker/nonsmoker) that are key drivers of pairwise relationships.

(2) Compare selected questionnaire items (e.g., sources, activities) with exposure and

environmental measurements to determine their relative value.

(3) Compare the results among the three studies.

(4) Conduct multivariate analysis to determine the combined impact of residential

pollutant sources, housing characteristics, and activity patterns on exposures.

Data or Input

Needs:

For all three studies, measured concentrations in all media, activity information (diaries

and questionnaires), housing characteristics, and occupational data. Information also

needed on sample dates, geographic locations, and sampling protocols.

Feasibility

(of analyses with

current NHEXAS

databases):

Need to review availability of samples for some media, proportion of analyses above

detection limits, and substitution of measurements obtained from nearby households

during the same periods of time (e.g., for outdoor air and soil measurements in Region V

study).
E-10

PREDICTORS OF EXPOSURE AND DOSE PROJECT P-01

(cont’d)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Year

0.2 0.3 1.0 3 (metals, VOCs, pest.) 1

Research Outputs

(1) Complete multivariate analysis of individual NHEXAS pilots

(2) Complete questionnaire/measurement analyses

(3) Compare analysis among studies to help combined study analysis 

(4) Final output: Complete combined study multivariate analysis and final report

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects EA-1, A-9, and

LL-11.
E-11

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-02. Compare Traditional Indirect Method of Estimating Dietary Exposures with

Duplicate Diet Data and Compare Methodologies Utilized in NHEXAS

Short Project

Description:

Comparison of direct exposure data from NHEXAS duplicate diet measurements with

indirect exposure estimates derived from recorded food consumption combined with

concentrations of NHEXAS chemicals measured in other studies, such as the Total Diet

Study (TDS). Also compare food intake rates from NHEXAS questionnaire surveys with

those from USDA and NHANES food intake surveys of comparable years, geographical

regions, and population subgroups. Describe, compare, and evaluate the validity,

reproducibility, and cost effectiveness of the duplicate diet collection methods.

Goal/Objective: To compare dietary exposure estimates from a dietary exposure model (i.e., sum of the

concentration × quantity consumed for all foods eaten) with direct measurements of

dietary exposure (i.e., from duplicate diet samples); to evaluate the reliability and validity

of dietary intakes determined in NHEXAS; and to evaluate alternative and less costly

methods for measuring dietary exposure.

Significance of

Project:

Although the indirect dietary model approach to dietary exposure assessment is widely

used (e.g., for pesticide regulations), validation of such estimates with real monitoring

data have not been done. NHEXAS data provide an opportunity for such validation to

enhance the scientific basis for decision making. Comparison of dietary measurement

and estimation approaches also may help to identify less costly alternatives for dietary

exposure monitoring and to provide estimates of long-term exposures from short-term

measurements (or estimates). This project also addresses several issues related to

analyses of exposures including testing of hypotheses (adequacy of extant data and

models to predict exposure), evaluation of survey instruments, and prediction of dietary

exposure as a component of total exposure. 

Suggested

Approach:

(1) Code food intake data from NHEXAS food diary or food checklist into formats that

are consistent with USDA food codes.

(2) Compare NHEXAS food intake rates with those from USDA and NHANES for

comparable time frames, regions, and population subgroups, including evaluation

of weighting for nonresponse (where data allow such evaluation).

(3) Calculate dietary exposures using individual consumption data (from diary or

checklist) and extant food contaminant data (from FDA TDS, USDA Pesticide Data

Program data, NHEXAS Maryland minimarket basket survey, and other existing

residue data).

(4) Estimate exposure using NHEXAS duplicate diet measurements and compare these

results with results obtained from indirect method across population subgroups.

(5) Comparative analysis of dietary data from checklist, duplicate diet collection, and

mini-market basket approach in terms of validity, reliability, and cost effectiveness.

(6) Analyses of calculated dietary exposures in relation to various demographic

variables.

Data or Input

Needs:

NHEXAS food diary and checklist data and duplicate diet data from each study, coding

of food consumption to USDA or EPA/Dietary Exposure Potential Model (DEPM)

codes, duplicate diet measurements from each consortia, and existing food contaminant

data for those target chemicals measured in diet samples (USDA and FDA data, from

DEPM).
E-12

PREDICTORS OF EXPOSURE AND DOSE PROJECT P-02

(cont’d)

Feasibility

(of analyses with

current NHEXAS

databases):

The duplicate diet studies and diet questionnaires were administered to a sufficiently

large number of individuals in the Region V and Arizona studies to support these

analysis. In addition, the Maryland data obtained food intake longitudinally to allow an

in-depth comparison of short- and long-term average intake.

May be limited to quality/resolution of dietary consumption and duplicate diet

measurement data. Not all food diaries have been coded, and it may not be possible to

code to all the USDA codes. The food checklist is limited to 100 to 200 food items. The

discrepancy between number of items could make cross-coding difficult.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Year

0.1 0.5 0.5 2 (metals, pest.) 1

Research Outputs

(1) Determine the compatibility of the data sets 

(2) Harmonize food codes among NHEXAS, USDA, and NHANES

(3) Compare food intake rates among the various surveys

(4) Estimate exposure based on food consumption and concentration data

(5) Compare exposure from NHEXAS duplicate diet studies with those obtained from indirect method

(6) Final output: Report consistency or inconsistency between the two approaches and identify approaches

(if any) to improve the indirect method of estimating dietary exposure

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects EA-04, A-10, and

A-11.
E-13

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-03. Identifying Predictors of Exposure

Short Project

Description:

To identify primary predictors of exposure, using questionnaires and biological or

environmental measures for use in epidemiology studies and other studies where

individuals’ exposure levels are sorted into categories such as high, medium, and low.

Goal/Objective: Classification of individuals (and populations) into exposure categories for use in

epidemiologic studies and risk assessment. Two products: (1)identify primary

predictors of exposure for epidemiologic exposure assessment and (2) identify

potentially highly exposed populations for future health effect studies or risk

management.

Significance of

Project:

Epidemiologists, risk assessors, and risk managers need the ability to classify people

into exposure categories. EPA, ATSDR, CDC, NIEHS, and the National Institutes of

Health all could use this information.

Suggested

Approach:

Using the available NHEXAS data, including questionnaire, biological marker, and

environmental data, prioritize chemicals based on the population prevalence or

toxicological importance. For the chemicals (or chemical class), construct regression

models to identify the predictors of exposure. These analyses should identify which

questions predict measured exposure, both biological and environmental. Factor

analysis or principal components analysis should be used to identify the most important

questions that predict chemical exposure. NHEXAS data should be analyzed to

determine how well the environmental data predict exposure and how well questionnaire

and environmental measures predict exposure. Predictive models should be developed

that can be used in subsequent studies. Key issues would be accurate separation of the

population into low, medium, and high categories and development of models to identify

highly exposed individuals. Ultimately, efforts should be made to attempt, on an overall

basis, to identify which questions identify individuals who are highly exposed to many

chemicals and those that are specific for one chemical or one chemical class. Risk

managers and study designers will be able to use the results of this analysis to identify

sample collection strategies by incorporating predictive ability of the data from each

source (questionnaire, biological, and environmental) and the cost to collect and analyze

data collected via these methods.

Data or Input

Needs:

NHEXAS data from all study sites (or each individually): questionnaires, biological

samples, and environmental and personal exposure samples. No additional data needed

unless external validation of questionnaire responses is done.

Feasibility

(of analyses with

current NHEXAS

databases):

All data are currently available. Much of the questionnaire data is nominal or ordinal

and may not be well suited for the usual regression approaches.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.2 0.5 1.0 3 (metals, VOC, pest.) 1

Research Outputs

(1) Preliminary analyses by chemical/chemical category

(2) Final output: Identification of potentially highly exposed individuals and the tools to identify them
E-14

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project A-5.

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-04. Risk Factors for Biomarkers of Internal Dose: Demographics, Questionnaire Data,

Concentrations, and Exposures 

Short Project

Description:

Analyses to determine the association of biomarkers of internal dose with (1) demographics;

(2) questionnaire information on behaviors, activity patterns, health indices, etc.; and

(3) measures of personal exposures and media concentrations.

Goal/Objective: To develop simple methods of estimating internal dose that can be used in studies of health

outcomes.

Significance of

Project:

Analytic or epidemiologic studies of health endpoints need effective methods for estimating

internal dose, but direct measurement is often impractical. For example, studies of chronic

health effects may require estimates of long-term average or historical exposures. NHEXAS

provides a rich source of information that allows inferences about internal dose based on

data collected from questionnaires, measures of chemicals in external media, and other

sources.

Suggested

Approach:

For appropriate chemicals and classes of chemicals: 

(1) Bivariate analyses of the association of biomarkers of internal dose and risk factors,

including demographics, housing characteristics, questionnaire data, and measures of

exposure.

(2) Examine correlations among risk factors.

(3) Multivariate modeling of the association of biomarkers with risk factors.

Data or Input

Needs:

Biomarker concentrations, demographics, questionnaire data, and environmental media

concentrations and exposure measurements. 

Feasibility

(of analyses with

current NHEXAS

databases):

These analyses will be feasible only for chemicals where biomarkers of internal dose exist at

detectable levels for a sufficiently large sample. For a given risk factor, there also must be

sufficient variability. Also requires knowledge of biomarker characteristics (e.g., half-life) to

relate measurements to time of exposures.

Research Outputs

(1) Conduct bivariate analyses

(2) Examine interrelationships of covariates

(3) Final output: Results of multivariate modeling

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project EA-3.
E-15

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-05. Determinants of Dose Measurements (Biomarkers) from the NHEXAS Studies

Short Project

Description:

Absorbed dose may be estimated by questionnaire and measurement data including air,

water, diet, and contaminated surfaces. Predictive associations between measurements of

exposure and dose will be evaluated. Questionnaire response data will be considered as a

modifier of the exposure/dose association. This association will be evaluated further by

taking into account existing pharmacokinetic models and parameters. Methods and

approaches for assessing the dermal exposure contribution relative to the biomarker

measurements are of particular importance because dermal exposure methods are not well

developed. Measured biomarkers will be related to potential exposure using algorithms

used to estimate aggregate human exposure. 

Goal/Objective: To identify and evaluate environmental and questionnaire determinants of dose and to

better understand the time course associations between exposure and dose. The dermal

contribution to exposure will be analyzed.

Rationale for

Project:

Study results will aid in the interpretation of exposure biomarker measurements and will

help in the efficient design of future exposure and epidemiologic studies. Further

understanding in the interpretation of biomarker levels is valuable because they are

believed to provide a better predictor of health outcome than environmental concentration

measurements that do not account for contact, uptake/intake, and absorption processes.

Suggested

Approach:

Biomarker measurements represent the absorption and clearance of chemical

contaminants measured in the NHEXAS program. The predictive relationship among

these measurements will be evaluated with questionnaire responses, and with exposure

and environmental media concentrations using multivariate analysis methods. 

Pharmacokinetic models will be applied in order to explain the relationship between

exposure and dose (biomarker) measurements. Contributions of contaminated media can

be estimated using exposure algorithms routinely used in exposure assessment.

Data or Input

Needs:

Chemical measurements in biological, exposure, and environmental media, questionnaire

data, exposure factors, and pharmacokinetic parameters.

Feasibility

(of analyses with

current NHEXAS

databases):

Sufficient detectable results are needed in media of exposure relevance for biomarker

analytes. Need to consider timing of biomarker collection relative to exposure and

environmental measurements (e.g., Maryland study samples collected at beginning of

sampling), and the availability and suitability of available pharmacokinetic parameters for

the subpopulations (e.g., children). 

Research Outputs

(1) Multivariate statistical analyses; evaluation of short-term clearance models

(2) Final output: Journal article identifying predictors of dose

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project EA-10.
E-16

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-06. Exploratory Data Analysis Methods for Evaluating Relationships Among

Questionnaires, Exposure, Dose, and Risk Factors

Short Project

Description:

The NHEXAS databases include a wide spectrum of measurements: questionnaire

responses, exposure measurements, and dose/biomarker measurements. Several analysis

methods are now available for analyzing complex data sets to identify patterns,

relationships, sociodemographic variables, important factors, and combinations of factors

that influence or affect exposure distributions. These data will be analyzed without a priori

decisions about relationships among the variables to generate new hypotheses regarding

environmental exposures. 

Goal/Objective: Identifying and evaluating (1) associations among the NHEXAS variables, and

(2) appropriate analysis tools for investigating large and complex data sets. Specifically,

there is a need to identify the factors that contribute to high exposures, to establish

relationships among these factors and exposure magnitudes/distributions, and to

understand subpopulation differences.

Significance of

Project:

Classification of NHEXAS data into variable groups will help focus future exposure

assessments in national surveys, epidemiological studies, and risk assessments. (It also

provides a comparison between the questions and the rationale for their use.) It is

important to understand the data prior to using it for model evaluation or identification of

significant exposure pathways/processes. Methods or approaches for investigating

complex data sets should be compared to determine the most appropriate approach to

identify important contributing factors in the NHEXAS data. 

Suggested

Approach:

(1) The strengths and limitations of the data will be evaluated initially using univariate

analyses of individual variables. 

(2) Multivariate classification techniques will be selected and run (e.g., principal

components, CART, neural networks, or factor analysis) to identify groupings of

variables. Where possible, analyses are to be conducted by pertinent subpopulations

because the variables may group differently by subpopulation.

(3) Variable groupings will be evaluated in order to generate hypotheses, to guide in the

design of other studies, and to identify important questions and/or measurements for

future exposure assessments and risk assessments.

(4) Identify strengths and limitations for each method in relation to the NHEXAS data. 

Recommend appropriate methods for analyzing NHEXAS data with special attention

paid to the upper tails of the distributions.

Data or Input

Needs:

The fully compiled database of complete measurement data including all chemical

measurements, questionnaires, dietary and activity diaries, and demographic variables.

Feasibility

(of analyses with

current NHEXAS

databases):

Feasibility of the project will be limited by the number of observations within strata. The

large number of qualitative and quantitative data types included in the NHEXAS data sets

(ordinal, continuous and binary) require special consideration when identifying appropriate

methods or approaches used to analysis data. Attention should be given to the upper tails

of the exposure distributions.

Research Outputs

(1) Univariate analyses

(2) Final outputs:

•Journal article on comparative analyses

•Journal article on ability of exposure measurement to predict exposure factors

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-11. 
E-17

PREDICTORS OF EXPOSURE AND DOSE PROJECT

Project Name: P-07. Use of NHEXAS Data To Test Assumptions about Activity Pattern Factors and

Other Exposure Factors in EPA Risk Assessments

Short Project

Description:

This project encompasses a series of individual projects that will examine the use of

activity pattern factors and other exposure factors in EPA risk assessments as they are

done in the Air, Water, Hazardous Waste, Pesticides, and Toxics Programs. Examples of

tasks under this project area were raised at the workshop and include the following: 

(1) examine NHEXAS time/activity diaries and follow-up questionnaire data to determine

the repetitiveness (frequency) of behavior over a 6- or 7-day period and compare to

existing time/activity databases used to evaluate factors in EPA assessments, (2) examine

the relationship among climate, season, level of exertion, and drinking water intake,

(3) prepare exposure scenarios, evaluate scenarios with NHEXAS data, and compare

those results to results obtained using current exposure assessment methods, scenarios,

and assumptions as they are used in EPA programs, and (4) use NHEXAS data to design

scripted sampling protocols for subsequent model testing or trend monitoring.

Goal/Objective: Current regulatory exposure models in the Air, Water, Hazardous Waste, Pesticides and

Toxics Programs often use default values that are based on limited and perhaps

unrepresentative data. Often, assumptions are used to fill data gaps. NHEXAS data will

be used to test assumptions and scenarios used in current assessment procedures, to

improve the current EPA methodologies, and to identify factors where further study is

needed.

Significance of

Project:

The results of this project area will be useful to any program office that does assessments

that rely on factors on which data were collected in the NHEXAS study. These include all

EPA programs—Air, Water, Hazardous Waste, Pesticides, and Toxics.

Suggested

Approach:

These are examples provided by members of the Assessment Breakout Group: compare 6-

day sequences of individual time/activity patterns to 6-day sequences of daily patterns

stochastically chosen from multiple individuals to determine impacts and frequency of

repeated activities. Assess relationships of individual time/activity patterns to food and

water ingestion across subject classes (e.g., age, gender, race) and local climate

conditions. Compile individual time/activity and exposure data for subjects with complete

data sets as input for exposure model testing and validation. Compile behavioral

scenarios characteristic of more highly exposed subjects for use in developing scripted

sampling protocols in subsequent exposure model testing and analysis.

Data or Input

Needs:

Individual time/activity data and exposure measurements from NHEXAS and other

appropriate comparative databases (e.g., time/activity, local meteorological data.)

Feasibility

(of analyses with

current NHEXAS

databases):

Feasible. NHEXAS data set contains data on activity patterns, exposure factors, varying

climates, and the like that can be used to test and refine current EPA assessment

methods.

Research Outputs

(1) Conduct analysis

(2) Final output: Journal article comparing frequency and duration of various activities over 1- and 7-day

periods in NHEXAS with data collected in other activity pattern surveys

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project A-6b.
E-18

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-01. Temporal Variability in Exposure Concentrations and Aggregate Exposure

Using NHEXAS Data

Short Project

Description:

Analysis of NHEXAS databases to determine the temporal components of variability in

various measures of exposure. The analysis will include both single-medium, singlepollutant class analyses, as well as total or aggregate exposure estimates over all media. 

Goal/Objective: To determine optimum strategies and designs for future NHEXAS national

investigations. Questions to be addressed include when is it possible to estimate

exposure from a single set of cross-sectional measurements, and what is the optimum

number of such measurements that must be made for each pollutant medium class and

for total exposure? Of interest is an understanding of the temporal span of the

toxicological effect (i.e., what is the exposure duration of interest and does variability

occur over such time spans?).

Significance of

Project:

A future national investigation of exposures must be designed to assess exposures to

members of the population that are accurate and reflect patterns and variability present

in true exposures. Improved understanding of temporal variability across days, weeks,

and seasons is necessary to ensure good estimates. This project has important

implications for risk assessment because it will help account for uncertainty because of

statistical “compression” of chronic exposure distributions compared to single-measure

exposure distributions because of intraindividual correlations of exposure over time. 

It also has implications for epidemiology because it will help reduce uncertainty because

of misclassification resulting from bias introduced by failing to account for temporal

variability in exposure indicators.

Suggested

Approach:

(1) Descriptive analysis of exposure concentration distributions by time period.

(2) Use statistical techniques to assess population variability and test whether the

population means vary over the duration of the studies.

(3) Assess intraindividual temporal variability.

(4) Evaluate aggregate exposure by summing potential or absorbed doses, as

appropriate (with appropriate weighting for time, etc.), over individual pathways.

(5) Evaluate temporal variability in total exposure.

(6) Assessment of intraindividual variability versus temporal variability in total

exposure.

(7) Assess statistical strategies for determining optimum sample number for temporal

variability.

(8) Implement chosen strategy to determine optimum number of exposure measures to

determine exposures of fixed length.

Data or Input

Needs:

Repeated measurement exposure data for all studies, particularly the NHEXAS-Maryland

investigation, identified with specific individual identifiers and temporal spacing. 

Certain questionnaire data to identify changes in exposure patterns attributable to otherthan-usual exposure variability (e.g., a change in job status or introduction of a new

source into the home).

Feasibility

(of analyses with

current NHEXAS

databases):

Data exist in the NHEXAS-Maryland study and, to a limited degree, in the other studies,

that would allow this to be completed. Repeated measurement data are available for

most media in the Region V study. Sample sizes of 2 to 6 repeated measurements are

available.
E-19

SPATIAL AND TEMPORAL VARIABILITY PROJECT ST-01

(cont'd)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

.1 .3 2 3 1.5

Research Outputs

(1) Perform univariate temporal analyses of selected pollutant-class/-medium combinations

(2) Construct aggregate exposure estimates

(3) Evaluate temporal variability in exposure estimates for target chemicals

(4) Construct optimum sampling strategy for target chemicals

(5) Final outputs: Manuscripts on univariate temporal variability and manuscripts on aggregate exposure

variability and optimum sampling strategy

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project A-4.
E-20

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-02. Use NHEXAS Dietary and Activity Pattern Data To Develop Predictive

Relationships Between Single-Day Observations and Long-Term Patterns of Behaviors

Short Project

Description:

To use statistical techniques to determine the relationships between measurements of

exposure-related behaviors (e.g., dietary and activity patterns) on a single day and

subsequent longitudinal measurements. Use the short-term relationships to develop

predictive models of longer term behaviors. The NHEXAS data set provides a unique

source of information for this study.

Goal/Objective: To develop models of the relationship between short- and long-term measurements of

exposure-related behaviors that can be used in models of long-term exposures.

Significance of

Project:

Collection of longitudinal data on exposure-related activities are resource intensive and

subject to a number of technical difficulties. However, such data are critical to the

accurate estimation of dose rates over periods longer than a single day.

Suggested

Approach:

Longitudinal data on exposure-related behaviors will be extracted from the data set. 

Statistical techniques such as, but not limited to, random walk, Markov chains,

correlation, and pattern recognition will be investigated as potential tools to identify

relationships between short- and long-term patterns of behaviors. It is anticipated that

the relationships will vary greatly across behaviors. No one method is likely to predict

the relationship between short- and long-term behavior. Attention should be given to

developing methods of estimating the upper bound of long-term behaviors as a function

of short-term data. Patterns in time/activity data from the Maryland NHEXAS study

should be compared/contrasted with data collected in the Region V and Arizona 

NHEXAS studies. Certain endpoints such as dietary records should be compared to the

results of other longitudinal dietary studies to determine consistency across different

populations.

Data or Input

Needs:

The NHEXAS data set and other studies of long-term dietary patterns.

Feasibility

(of analyses with

current NHEXAS

databases):

The data for this task are available. No limitations are anticipated.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

.1 .2 .4 1 1

Research Outputs

(1) Extract NHEXAS data for data set 

(2) Obtain other dietary surveys

(3) Reconcile differences in dietary survey methods

(4) Perform statistical analyses

(5) Final output: Journal article on relationship of single measurements of dietary exposure to long-term dietary

exposure

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-10.
E-21

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-03. Characterization of the Variance Components of NHEXAS Data to Optimize

Future Designs

Short Project

Description:

Characterize the variance components of NHEXAS data, including the inter- and

intrapersonal, temporal (e.g., integration time, seasonal, weekly), activity-related, and

spatial variabilities by sample size for each of the pollutants by pathway/medium and by

integrated total exposure. Also, determine the reliability of a short-term measure of

exposure for assessment of long-term exposure for populations and individuals. 

Results will be used to optimize future NHEXAS design.

Goal/Objective: The primary goal of the proposed project is to use the NHEXAS data to determine the

appropriate sampling strategies for the different pollutants and pathways. To achieve

this goal, the proposed project will characterize the variance components of the

NHEXAS exposure data to

• estimate the optimum sample size and number of repeated measures (SAB comments

II.A.2 and 4);

• determine how exposure distributions vary across time and space and identify factors

that influence this variation (II.A.2);

• examine the variability of exposure distributions based on short-term measurements

compared to those based on long-term measurements or averages;

• assess whether the variance components differ by subpopulation, including

susceptible and highly exposed subpopulations (II.A.4); and

• investigate how the exposure characteristics of the various subpopulations are

influenced by activity patterns, geographic area, and SES (II.A.4).

Significance of

Project:

The proposed project directly addresses SAB concerns and, as a result, will improve

substantially the ability to optimize the design of future NHEXAS and other exposure

studies. It will incorporate findings from each of the three NHEXAS consortia and will

allow the sampling plan of each consortium to be examined in a systematic and

quantitative manner.

Suggested 

Approach:

Exposure data from each of the three NHEXAS studies will be analyzed to determine the

inter- and intrapersonal, temporal, and spatial variabilities in exposure distributions. 

Analysis will be performed by pollutant, both pathway-specific and as integrated total

exposure, as well as by subpopulation. Variabilities will be assessed using standard

statistical approaches, including the coefficient of variation and ANOVA and mixed

model approaches. Graphical techniques will be used to evaluate and determine

appropriate pollutant- and media-specific sampling strategies. As possible, pollutants

will be grouped based on identified appropriate sampling strategies. This project should

be limited to representatives of the various chemical classes (e.g. metals, pesticides and

VOCs).

Data or Input

Needs:

From each pilot study (and primarily the Maryland NHEXAS study for temporal data),

the following data will be needed:

• environmental concentration and exposure data (including metabolites),

• questionnaire data, and

• time/activity data.

Feasibility

(of analyses with

current NHEXAS

databases):

High, all the necessary data exists.
E-22

SPATIAL AND TEMPORAL VARIABILITY PROJECT ST-03

(cont'd)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

.3 .9 3 3 2

Research Outputs

(1) Analyses of the data

(2) Final outputs:

•Reporting of the optimized sampling strategies by pollutant and pathway

•Publishing in peer reviewed journals

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects EA-6 and LL-12.
E-23

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-04. Spatial Variability

Short Project

Description:

NHEXAS data will be used to investigate spatial variability in concentrations, doses,

and activity patterns. Possible areas of investigation include different states and

counties, rural versus urban areas, locations near sources, and different climates and

elevations.

Goal/Objective: The goals of this research are to identify spatial and geographic factors contributing to

high exposures for consideration in exposure assessment, to determine

representativeness of local/regional data for use in assessments of other regions, and to

identify geographically defined point and area sources.

Significance of

Project:

These analyses will help assessors understand the geographic variability of pollutant

concentrations and exposures and the impacts of such things as population density,

climate, elevation, and local cultural factors. It also will examine the impact of

identifiable, geographically located sources on exposure levels. Information on spatial

variability also will contribute to more efficient design of future studies.

Suggested

Approach:

(1) The following is an approach for comparing different geographical areas: select

variables for comparison (e.g., a particular chemical/media combination), consider

differences in sampling methodology that could account for differences among

NHEXAS studies, account for confounding factors, and make statistical

comparisons of distribution parameters.

(2) The following is an approach for analysis of sources: identify potential sources of

NHEXAS chemicals based on other data, such as data in the literature and the EPA

Toxic Release Inventory Data; and perform analysis of correlation of exposure

concentrations and locations of sources using geostatistical methods. 

Data or Input

Needs:

(1) Sufficient number of people in each geographic group to make meaningful

comparison. Data set needs to have sufficient percentage of detectable levels of

NHEXAS target chemicals. Sampling protocols and equipment for each location

need to be similar enough so that differences are not attributable to the methods

used. 

(2) Independent database to provide latitude and longitude and perhaps some estimate

of emissions for target sources. Latitude-longitude and concentration/exposure data

for NHEXAS participants.

Feasibility

(of analyses with

current NHEXAS

databases):

(1) This study could be done for a few categories (e.g., state-by-state) in Region V. 

There may be a problem comparing environmental samples among studies because

of different sampling methodologies. Parameters selected for comparison need to

have similar sampling protocols (e.g., blood, urine, drinking water, etc.).

(2) Data on latitude and longitude of sources is critical as is data on latitude and

longitude of participants (may be available only for Arizona). There also would need

to be some method to protect the confidentially of respondents that could be

compromised by revealing the latitude-longitude of their residences. 

Research Outputs

(1) Final outputs: Comparison of measurements, activity pattern duration/frequency, or total exposures in

different geographical areas. Description of similarities and differences between sampling and analytical

methods of NHEXAS consortia and potential impact on comparisons of results

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project A-12.
E-24

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-05. Investigate Stability of Individuals in Population Exposure Ranks

Over Time

Short Project

Description:

Temporal variability in measurements of individuals may have a significant effect on

estimates of exposure factors and distributions. This project will investigate the effect of

using cross-sectional studies on estimates of exposure factor distributions. Crosssectional studies are cost efficient because they collect minimal observations per

individual, but provide no indication of temporal variability. Measures of intra

individual temporal variability do not necessarily tell the complete story, as individuals

may vary in concert, because of factors such as seasonal changes. It is also useful to

examine the stability of individual’s position or rank in the population exposure

distribution to determine how this stability influences predictive ability of various

exposure distribution parameters.

Goal/Objective: To examine the importance of temporal variability and evaluate sources of variability in

exposure factor measurements of an individual over time. To examine this variability on

stability of an individual’s rank or position in exposure factor population distributions.

Significance of

Project:

It is important to understand the temporal variability in individual’s measurements to

assessment of potential bias of cross-sectional studies as estimates of exposure factor

population distributions. A clear understanding of temporal variability will be useful in

deciding when and where cross-sectional studies are appropriate for estimation of

population exposure distributions and what modifications may improve these studies in

a cost-efficient manner. This work also would provide highly relevant information on

estimating the upper tails of the distribution.

Suggested

Approach:

(1) Identify feasible and relevant variables from NHEXAS for study..

(2) Develop/assess methods for examining temporal variability and stability of

individuals

(3) Use mixed models to develop repeated measure/temporal correlation estimates and

consider automation of methodology for examination of large numbers of variables.

Data or Input

Needs:

The entire NHEXAS date set; especially the Maryland NHEXAS longitudinal data.

Feasibility

(of analyses with

current NHEXAS

databases):

Feasible for variables where longitudinal data are collected for at least some individuals. 

Focus is likely to be on the Maryland study, with confirmation/validation use of Region

V and Arizona NHEXAS studies.

Research Outputs

(1) Develop methods for examining temporal variability and stability of individuals

(2) Apply mixed models to develop repeated measure/temporal correlation estimates

(3) Final outputs:

•Determination of factors influencing temporal variability in individuals exposed to environmental 

pollutants

•Identification of limitations of cross-sectional population exposure surveys and recommendation of 

optimal spatio-temporal survey designs for future NHEXAS-type studies

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-8.
E-25

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-06. Spatial and Temporal Variability in Multichemical Exposure

Short Project

Description:

Project will better characterize the magnitude and variability in exposure to multiple

chemicals measured in all environmental media by the three NHEXAS studies for different

locations of the country. Both within- and among-study variability will be examined, and

analyses will be conducted to determine whether exposure to one chemical in a given class

is predictive of exposures to other compounds in that class or other classes.

Goal/Objective: The goal of this project is to provide information that will improve the efficiency (e.g., costeffectiveness) of future exposure, risk assessment, and epidemiologic investigations of

health risks of cumulative chemical exposure. This study will provide some of the first

information on multichemical and multipathway exposures required for cumulative risk

assessments.

Significance of

Project:

The need to assess risks of cumulative chemical exposures is well recognized within the

scientific and regulatory communities. Little information is available for such assessments. 

Analysis of the temporal and spatial aspects of the NHEXAS data is important to reduce 

uncertainty in the exposure estimates for these assessments.

Suggested

Approach:

The suggested approach is to examine multiple chemical exposure, first for each route of

entry and second for aggregate exposure. This approach should be limited to two or three

chemical classes, but utilize all of the NHEXAS data even if a compound was not collected

in all media (e.g., VOCs). Analyses will be performed on measurements of environmental

concentrations, exposure, and biomarkers (related to internal dose). Investigators should

determine the appropriate chemical classes for study.

Data or Input

Needs:

Concentration, exposure, and biomarker measurements from each NHEXAS study.

Feasibility

(of analyses with

current NHEXAS

databases):

The feasibility of the proposed project is high for analyses of data within the Maryland

study. Some limitations are anticipated in the types of samples available from the Region V

study. (Longitudinal samples were not collected for Arizona.)

Research Outputs

(1) Initiate investigations within each medium and combine data across media where feasible for each study

(2) Complete single-route and aggregate analyses of cumulative exposure

(3) Final outputs:

•Compare findings among studies

•Report findings, write reports and manuscripts on cumulative chemical exposure

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project EA-5.
E-26

SPATIAL AND TEMPORAL VARIABILITY PROJECT

Project Name: ST-07. Development and Evaluation of Models for Interpreting and Quantifying Interand Intraindividual Variability in Pesticide Exposure/Dose Using NHEXAS Data

Short Project

Description:

Analyze cross-sectional and longitudinal biomarker and exposure data for pesticides

considered in NHEXAS (such as chlorpyrifos and atrazine) to develop and test

population-based pharmacokinetic (i.e., pharmacostatistical) models that explicitly

discern and quantify intra- and interindividual variability in human doses.

Goal/Objective: To develop, test/evaluate, and make available to EPA and the scientific community at

large, a mechanism-based computational tool for characterizing and quantifying interand intraindividual variability (i.e., cross-sectional and longitudinal variability) in

pesticides exposure/dose of human populations.

Significance of

Project:

Quantitative characterization of inter- and intraindividual dose (and corresponding

exposure) to common pesticides will reduce the uncertainty in, and thus improving,

relevant dose/response studies and corresponding risk assessments. The mechanistic

approach to be developed and evaluated should be applicable to a wide range of

exposure situations and U.S. population segments.

Suggested

Approach:

(1) Develop general formulations for population-based (pharmacostatistical) models of

selected pesticides considered in NHEXAS (primary candidates are chlorpyrifos and

atrazine) that explicitly incorporate/describe inter- and intraindividual variability of

biological uptake/distribution/fate. This step primarily should consider existing

“individual-based” “classical” (compartmental) models, as well as the possibility of

formulating simplified population physiologically based models.

(2) Perform analyses of appropriate NHEXAS data components to develop

parameterizations for the above formulations (the Maryland study database being

the primary candidate because it contains extensive longitudinal data); assess and

interpret magnitudes of different types of variability.

(3) Test the population pharmacostatistical model, with parameterizations derived as in

the step above, with relevant independent data from other NHEXAS components to

evaluate its ability to reproduce variability observed in these studies.

(4) Review the available literature for other relevant data sets that may exist on dose

variability for the pesticides of concern and extend the model evaluation to include

these data sets.

(5) Finally, evaluate the new model/method for its applicability to children’s exposure to

pesticides (using the NHEXAS Minnesota study data) and derive recommendations

for appropriate model refinements/modifications and possibly additional data

collection that would help to extend the model to children’s exposure.

Data or Input

Needs:

Pesticide exposure- and dose-related data from all three NHEXAS studies; other

exposure/dose-related data from these studies (from both monitoring and

questionnaires), such as activity patterns and additional literature data

Feasibility

(of analyses with

current NHEXAS

databases):

At a minimum, it should be feasible with the collected data to at least evaluate the

applicability of a population-based pharmacokinetic model for pesticide dose estimation

to multiple regions and population segments of the United States. In some cases,

biological half-life considerations may influence the modeling choices. In the best case,

a widely applicable tool will be available; in the worst case, data needs for characterizing

nationwide variability to dose will be identified. 
E-27

SPATIAL AND TEMPORAL VARIABILITY PROJECT ST-07

(cont'd)

Research Outputs

(1) Data analysis/evaluation

Comparison and evaluation of existing approaches for individual-based pharmacokinetic modeling of the

selected pesticides

(2) Final outputs:

•Tested operational population-based model with explicit descriptions of inter- and intraindividual 

variability

•Peer-reviewed manuscript

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-14.
E-28

AGGREGATE EXPOSURE, PATHWAY ANALYSIS, 

AND CUMULATIVE RISK PROJECT

Project Name: AE-01. Aggregate Exposure

Short Project

Description:

This project will estimate aggregated exposures from all media and all pathways for a single

chemical. Environmental concentrations, personal exposure data, biological levels, and

questionnaire data from NHEXAS, supplemented by data from other sources, will be used in

the assessments. Multimedia exposure models representing current state-of-the-science

regarding chemical, environmental, and population dynamics will be employed. The project

will determine the relative contributions of environmental media and routes of exposure to

“total exposure” or dose for each NHEXAS study and compare results among studies. 

These analyses will help to identify critical exposure pathways, factors, and sources that

contribute to high end exposures. 

Goal/Objective: (1) To utilize existing multimedia/multipathway exposure models to aid in the interpretation

of NHEXAS data and to help identify critical exposure pathways, processes, factors, and

sources that contribute to high end exposures.

(2) To assess aggregate exposure and identify the important media, pathways, and routes

that contribute the most to total exposure;

(3) To identify or develop methodologies (or models) to use biological data in aggregate

exposure assessment through analysis of the relationships among biological testing

results (i.e., blood and urine samples), environmental concentrations, personal

concentrations, and exposure/dose 

(4) To compare the approaches, data, and estimates used to apportion pathway-specific

exposures used in the NHEXAS studies and to identify similarities and differences, and

compare or pool results where possible.

Significance of

Project:

(1) Addresses the important regulatory issues associated with single and multimedia

exposures (e.g., air, water, contaminated soil, and food)

(2) Advances exposure assessment methodology (multimedia and multipathway)

(3) Helps the agency to prioritize resources to address the most important media or

pathways, and to design intervention strategies to protect public health

(4) Determines how the results (parameter estimates) from the individual NHEXAS studies 

 can be systematically compared to each other or pooled to provide combined estimates 

of associations between pathway-specific measurements/estimates and aggregate 

exposure or dose. 

(5) Utilizes existing tools that assimilate or represent the current level of understanding of 

 exposure processes to extract relevant and useful information from the NHEXAS 

studies.
E-29

AGGREGATE EXPOSURE, PATHWAY ANALYSIS, AND CUMULATIVE RISK

PROJECT AE-01

(cont'd)

Suggested

Approach:

Ideally, this project should include at least one pesticide and one metal. For each chemical

class, identify specific case studies that warrant investigation (e.g., elevated concentrations

in multiple media, elevated exposure, sensitive subpopulations).

(1) Identify or develop an aggregate exposure model to assess aggregate exposure for each

individual. 

(2) Construct concentration and exposure factor distributions for each exposure variable

using questionnaire and measurement data from NHEXAS supplemented by data from

other sources where necessary.

(3) Calculate aggregate exposure for each individual. 

(4) Compare aggregate exposure results to biomarkers.

(5) Compare estimates of pathway or route specific exposures with total exposure or

absorbed dose to identify pathway contributions to exposure.

(6) Identify important contributors to high end aggregate exposure. Data on activity

patterns, housing characteristics, and other exposure factors can be obtained from the

questionnaire and assessed using a variety of methods that handle different data types

(binary, integer, categorical, ordinal, and continuous). Potential methods may be based

on regression trees, neural networks, factor analysis, or order statistics (i.e., statistics of

extreme events). Fate and transport models and regression models may be used to

assess contributions of sources such as industrial point sources, motor vehicles,

smoking, pesticides and other consumer products used at the residence, building

materials, and combustion sources. 

(7) For each study, examine sampling and analytical methods to determine if the resulting

measurements are sufficiently similar to be compared. Compare results (parameters and

error terms) among individual studies where feasible.

(8) Pool data where measurements are similar to make generalized statements about

exposure where feasible.

(9) Evaluate uncertainties and limitations. Develop plausible explanations for NHEXAS

results.

Data or Input 

Needs:

(1) Environmental concentration data in all media

(2) Biological testing data 

(3) Questionnaire data

(4) Information about sampling and analytical methods.

(5) Supplemental data from other sources– Toxics Release Inventory, population density,

pesticide use, absorption rates.

(6) Coefficients (e.g., uptake rates, absorption rates, etc.)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.1 0.5 0.5 3 (metals, VOCs, pest.) 1

Research Outputs

(1) Identify case studies, select models, and complete parameterization of case studies and complete initial

analysis

(2) Final output: Journal article on cumulative exposure and risk to selected chemicals.
E-30

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects A-3, EA-11, M-6,

and M-7. 

AGGREGATE EXPOSURE, PATHWAY ANALYSIS,

AND CUMULATIVE RISK PROJECT

Project Name AE-02. Comparison of children’s’ and adults’ exposures to pesticides and other

chemicals in the Region V, Arizona, and Maryland studies

Short Project

Description:

Compare children’s and adults’ exposures to pesticides, volatile organic chemicals,

metals, and PAHs using biomarker and environmental data collected in the Minnesota

Children’s Pesticide Exposure Study, Region V Study, and Arizona and Maryland

Studies. Data from the children’s studies in Arizona and Baltimore may also be

compared as they become available.

Goal/Objective: To determine if children’s exposures differ/do not differ from adults for pesticides and

other NHEXAS chemicals.

Significance of

Project:

Children have been identified as a potentially vulnerable subpopulation for exposure to

pesticides and other chemicals (e.g., lead). NHEXAS data may be used to better

understand differences between adults and children’s exposures, and ultimately to

determine if federal and state regulatory policies adequately protect children.

Suggested

Approach:

(1) Determine what data may be compared (see limitations below).

(2) Develop a set of consistent procedures for analyzing the data across studies to take

into account among-study differences (e.g., methods for handling values below the

detection limit; methods for handling non-normal distributions; methods for data

sets with a large number of values below the detection limit).

(3) Compare children’s and adults’ exposures (where appropriate). Focus on biomarker

data (urine, blood), and then expand to diet, personal air, and other measurements.

(4) Assess health risks for children and adults using appropriate toxicity values (e.g.,

RfDs, RfCs, cancer potency slopes). Compare health risks for adults and children.

Data or input 

Needs:

Data may be used from the Minnesota Children’s Pesticide Study, Region V Study,

Arizona Study, and Maryland Study. Data from the children’s studies which are being

conducted in Arizona and Washington may also be included (as the data become

available).

Feasibility (of

analyses with

current NHEXAS

databases):

Data among these studies may not be comparable because of differences in types of

measurements (chemicals, media), detection limits, methods/strategies of collection,

methods of analysis, and spatial and temporal factors. Consistent procedures for data

analysis must be developed for comparisons to be valid. Data are available on children

for metals and VOCs as well as pesticides. Also need to consider the effects of regional

differences on differences between children and adults in different regions. Child

subjects in the Region V and Arizona studies might possibly be used to address this,

but there may be a limitation based on the number of children in those two studies

(about 15%).

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.1 0.5 0.5 3 (metals, VOCs, pest.) 1

Research Outputs
E-31

Final outputs: 

•Assessment comparing total exposure (dose) for children in Minnesota. 

•Study of total exposure (dose) for adults in Region V or other appropriate studies.

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project A-8.

AGGREGATE EXPOSURE, PATHWAY ANALYSIS,

AND CUMULATIVE RISK PROJECT

Project Name AE-03. Construction of an empirical multimedia/multipathway exposure distribution

model including temporal variability based on NHEXAS data.

Short Project

Description:

The NHEXAS study collects data that can be used for the development of

multimedia/multipathway exposure models and can also incorporate temporal variability

in exposure factor measurements. Pre-NHEXAS models were based on data from studies

that were often limited in scope to single media/single pathway. Using the NHEXAS

data, the pre-NHEXAS models can be extended to include multimedia/multipathway

correlation among variables, both among and within individuals. This project examines

the issues involved in constructing this type of model based on the data available in the

NHEXAS study.

Goal/Objective : (1) Determine limitations of NHEXAS study design in construction of empirical

multimedia/multipathway exposure distributions which includes temporal variability.

(2) Construct empirical multimedia/multipathway exposure distribution model including

temporal variability using NHEXAS data to extent possible.

(3) Examine issues in constructing empirical models involving temporal variability,

including development of methodology for estimating multivariate distributions

Significance of

Project:

Project would extend empirical exposure distribution models to include temporal

variability in individual exposure measures and development of multivariate joint and

conditional distributions for use in empirical exposure distribution models. It will also

highlight the limitations in the NHEXAS study design for construction of such models

and provide information to improve future multimedia/multipathway exposure studies. 

Suggested

Approach:

(1) Use of NHEXAS Maryland data.

(2) Assessment of data for use in development of multivariate exposure factor

distributions.

(3) Extension of pre-NHEXAS model framework to include multivariate distributions.

(4) Estimation of parameters for empirical model exposure factors distributions

Data or input

Needs:

NHEXAS study data. Pre-NHEXAS exposure models.

Feasibility (of

analyses with

current NHEXAS

databases):

No feasibility issues beyond data and input needs.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.1 0.3 1.0 3 (2 pest., 2 metals, 2 VOCs) 2

Research Outputs
E-32

(1) Development of methodologies for multivariate distributions

(2) Estimation of distribution parameters from NHEXAS data

(3) Development of framework for empirical distribution model

(4) Running and analysis of model

(5) Multimedia/multipathway exposure distribution model including temporal variability

(6) Empirical multivariate distributions and associated uncertainties based on NHEXAS data that can be used

by other modelers

(7) Report/journal article assessing results of model analysis

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Workshop Project M-17.

AGGREGATE EXPOSURE, PATHWAY ANALYSIS,

AND CUMULATIVE RISK PROJECT

Project Name: AE-4. Cumulative Risk from Exposure to NHEXAS Chemicals

Short Project

Description:

Assess cumulative risks of various health effects associated with multichemical

exposures measured in NHEXAS

Goal/Objective: (1) To test whether the distributions of concentrations co-vary across subjects for

different chemicals or not.

(2) To identify groups of chemicals that vary together across the population and/or that

cluster together in the upper percentiles of exposure (e.g., upper 10th or upper 25th,

depending on availability of data) and analyze questionnaire data for ability to

predict whether a person falls in the upper tail of the joint distributions.

(3) To prioritize pollutants and pathways as to their contribution to cumulative risk of

various health effects to focus pollution control and other public health activities on

higher risk contributors.

(4) To assess cumulative risk resulting from exposure to multiple chemicals of similar

action/toxicity.

Significance of

Project:

A key question in addressing risks is whether the distributions across people in

exposures to chemicals A, B, C... are independent of one another or whether the

distributions are correlated. Are there individuals who fall in the upper tails of more than

one chemical distribution? If so, this could have important implications for risk

assessment. The results of this project will assist public health agencies (national, state,

and local) in effectively and efficiently targeting resources to control pollutants and

pathways of higher risk. This project, in conjunction with the Aggregate Exposure

Project, will start laying the foundation for agency efforts in cumulative (multistressor)

risk assessment. Examples where results of this project will be useful include

assessments of pesticides with similar mechanisms of action under FQPA, assessments

of multiple exposures to air toxics, and the recently begun effort to develop agency

guidance for cumulative risk assessment.
E-33

Suggested 

Approach:

• Construct bivariate correlation matrices for all chemicals (using pooled data across

study if possible) for NHEXAS media and carry out factor analysis to identify groups

of chemicals that vary together across the populations.

• Dichotomize exposure distributions into >X percentile or not and analyze whether

assignments are correlated across chemicals

• Characterize chemical groupings, if any, and use regression analysis to identify

predictors of high exposure.

• Develop cumulative risk assessment of chemical exposures for individual study

participants measured in NHEXAS projects. One approach is to identify chemicals

with common endpoints and/or mechanisms of action and use toxic equivalency

factors to sum the risks. Some common metric for risk must be found to combine

exposures of chemicals with varying toxicities. Approaches should conform to

Agency guidance and scientific understanding for assessment of mixtures of stressors. 

Calculate a weighted index of “cumulative” exposure using the absorbed dose

estimated from NHEXAS data

• Characterize relative contributions to cumulative risk of individual pathways and

pollutants per participant and describe distributions across study populations. Report

relative contribution of individual pathways and pollutants for representative low-end,

average, and high-end NHEXAS subjects.

• Develop relative ranking of pathways and pollutants in terms of contribution to

cumulative risk; identify key driving pathways and pollutants.

• Compare across studies.
E-34

AGGREGATE EXPOSURE, PATHWAY ANALYSIS, AND CUMULATIVE

RISK PROJECT AE-04

(cont'd)

Data or Input 

Needs:

Exposure measurements from NHEXAS studies

Population descriptions (e.g., body weights, ages, food intakes, etc.) from NHEXAS

studies

Toxicity data

Data on possible synergistic or antagonistic interactions among chemicals

Feasibility (of

analyses with

current NHEXAS

databases):

Limitations include number of pollutants for which quantitative dose-response values are

available. Initially, the project would probably consider those chemicals with common

health endpoints and/or modes of action. Also assumptions on nondetects will have to

be made (e.g., evaluate using nondetects set to zero versus set to 1⁄2 DL versus omitting

large nondetect chemicals from analysis). Cumulative risks would be assessed for variety

of health endpoints.

Research Outputs

(1) Intermediate steps:

•Collect toxicity data and identify appropriate set of chemicals for study

•Select appropriate models and parameterize models; complete initial

•Complete initial descriptive analysis including bivariate correlations

•Complete multivariate analysis of co-variance

(2) Final outputs: Report and publication on multivariate analysis of co-variance. Weighted exposure indices

for 1 to 3 sets of chemicals, depending on data availability. Multipathway, multichemical assessments with

estimates of total risk. Comparison of multichemical risk via single pathways with total risk for selected

NHEXAS compounds. Comparison of risk via single chemical with total risk from selected NHEXAS

compounds.

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects A-1, A-6a,

and EA-12.
E-35

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-01. Compare Pre-NHEXAS Model Results with NHEXAS Measurements

Short Project

Description: 

Compare pre-NHEXAS model results for benzene, lead, and chlorpyrifos with NHEXAS

measurements. Update pre-NHEXAS models with information from the measurement

data.

Goal/Objective: Assess validity of pre-NHEXAS models by comparing with measurements. Improve

these models based on data to better predict exposures.

Significance of

Project:

If models and data compare well, this provides a validated model for use in predicting

human exposures to these pollutants. This then can be applied to populations outside

of the NHEXAS study region. Differences between measured and modeled results can

be used to improve model predictions and provide information on limitations in the use

of disparate studies. Overall, this comparison will provide confidence in using models to

estimate multimedia exposures.

Suggested

Approach:

(1) Compare environmental concentrations as predicted from pre-NHEXAS benzene,

lead, and chlorpyrifos models with corresponding measurements, with special

attention to high-end concentrations.

(2) Extend pre-NHEXAS models to go from exposure to dose and compare NHEXAS

biomarker measurements to this version with special attention to high-end

measurements.

(3) Examine different parameters to determine possible reasons for discrepancies

between models and measurements. This should include comparison of measured

and modeled time/activity diaries and concentrations in air, food, water, and other

media. In addition, algorithms for calculation should also be examined.

(4) Determine if model predicts better/worse for a certain population subgroup, based on

location, age, race, sex or other factors.

(5) Improve model estimates based on results of tasks 1 through 4.

Data or Input

Needs:

Questionnaire and time/activity data, environmental concentration data, and analyte

concentrations.

Feasibility

(of analyses with

current NHEXAS

databases):

Pre-NHEXAS model code, documentation, and their results should be made available. 

Questionnaire data and concentration data that correspond to the pre-NHEXAS models

will be available.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.1 0.4 0.60 3 (pest, metal, VOCs) 2

Research Outputs

(1) Compare environmental concentrations from measured and modeled results

(2) Extend exposure model to dose and compare with urine/blood concentrations

(3) Determine which inputs/algorithms/population subgroups are responsible for discrepancies between model

and measurements

(4) Final outputs:

•Report on comparison between measured and modeled data

•Improve model based on results

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-16.
E-36
E-37

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-02. Comparison of NHEXAS Findings with National Air Toxics Assessment

(NATA) Estimates for Ambient Air Levels and Exposures for Selected VOCs and

Metalsa

Short Project

Description:

Compare patterns and trends in monitored neighborhood ambient air levels of VOCs and

metals to the annual average estimates of the same compounds derived through the

NATA; evaluate the relevance of NATA predictions to the types of exposure situations

characterized in NHEXAS.

Goal/Objective: To evaluate the relevance of NATA predictions to the types of exposure situations

characterized in NHEXAS; to identify gaps and potential improvements in both

screening modeling methods for ambient air quality characterization and in data

collection for exposure characterization.

Significance of

Project:

The NATA study has attracted remarkable attention regarding its reliability to predict

exposures actually experienced by individuals and populations. This project will help in

understanding and characterizing both the relevance and the limitations of NATA (and

potentially of similar approaches), as well as in identifying specific steps in improving

exposure estimates to airborne contaminants through screening modeling approaches.

Suggested

Approach:

(1) Extract ambient air concentration estimates from the 1996 database (or from the

follow-up database utilizing more recent TRI emission data, depending on its

availability at the time of project implementation) for a set of selected airborne VOCs

and metals monitored in the NHEXAS studies and for the approximate locations of

the monitors.

(2) Incorporate both the NATA estimates (i.e., based on HAPEM4 and ASPEN model

analyses) and the corresponding NHEXAS observations in a Geographic

Information System linked with appropriate statistical/geostatistical software

routines to ensure maximum usability, visualization, and analysis options for these

data and estimates.

(3) Perform qualitative and statistical comparisons of relevant ambient air concentration

estimates/data from NATA and NHEXAS, with focus on identifying general patterns

and trends.

(4) Perform screening calculations of exposure for selected subsets of the NHEXAS

components, using the NATA estimates as the starting point and utilizing partial

information from the NHEXAS databases (such as activity patterns and other

questionnaire-based information). Compare these results to personal exposure and

biomonitoring measurements and estimates that utilize additional NHEXAS data.

(5) Consider, evaluate conceptually, and, if possible, investigate through limited casespecific studies, potential improvements in NATA-type methodologies for screening

ambient and exposure characterization.

Data or Input

Needs:

For phase I (steps 1 to 3 of the approach), NHEXAS monitored selected VOCs and

metals with corresponding geographical location information. NATA results are

publicly available but certain additional information may need to be provided by EPA. 

For phase II (steps 4 and 5), access to more extensive information from the NHEXAS

databases (e.g., activity patterns and household attributes).

Feasibility

(of analyses with

current NHEXAS

databases):

The study is straightforward and feasible, depending only on on-time availability of

NHEXAS data for Phases I and II (as identified in the Data Needs).
E-38

EVALUATION/REFINEMENT OF CURRENT EXPOSURE MODELS

AND ASSESSMENTS PROJECT M-02

(cont'd)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.20 0.2 1.0 2 (2 VOCs, 2 metals) 1

Research Outputs

(1) Report summarizing evaluation of the relevance of the NATA estimates for exposure assessments

(2) Final outputs:

• Evaluation of methodologies for screening exposure assessments for airborne contaminants

• Specific recommendations for improving screening modeling methodologies and data collection

approaches

• Peer-reviewed manuscript(s)

aThis is a two-phase project (Phase I - Year 1; Phase II - Year 2). Critical results evaluating the relevance of

NATA estimates will become available from Phase I, whereas Phase II will focus on more exploratory aspects of

the problem, leading to recommendations for methodological improvements in screening exposure assessments.

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-15.
E-39

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-03. Develop Model Parameters from Qualitative and Quantitative NHEXAS

Monitoring Data, Questionnaires, Time/Activity, and Survey Data

Short Project

Description:

Develop exposure model parameter (e.g., ingestion rates, emission rates, etc.) values,

ranges, and distributions making use of both quantitative and qualitative data generated

in NHEXAS. Exposure parameters should be developed in accordance with the current

state of the art in exposure assessment and corresponding model input requirements.

Specific emphasis should be placed on key exposure parameters common in multimedia

exposure assessment and those that are likely to contribute to high-end exposures.

Goal/Objective: Generate deterministic values and stochastic distributions for exposure model

parameters, using available NHEXAS database. Exposure parameters that are selected

should be relevant to exposure assessments that are based either on mechanistic,

statistical, or empirical models.

Significance of

Project:

Improve exposure parameter values and the utility of questionnaires for quantitative

exposure analysis.

Suggested

Approach:

Develop methods to interface available selected exposure models with qualitative and

quantitative questionnaire data (e.g., time/activity patterns, identified sources and

exposure pathways) for the purpose of deriving magnitude, ranges, and distributions of

exposure parameters. The combination of artificial intelligence and statistical methods is

one possible approach for the automated analysis of large data sets.

Data or Input

Needs:

NHEXAS chemical monitoring data for all media (where available) and

qualitative/quantitative data generated from questionnaires and other sources (e.g., local

survey of potential sources).

Feasibility

(of analyses with

current NHEXAS

databases):

The use of mathematical and computer methods to combine qualitative and quantitative

data for the purpose of generating quantitative exposure parameters represent a new and

challenging approach. The proposed approach is feasible given the rich NHEXAS

database and existing state-of-the-art mathematical methods of quantifying descriptive

data in the context of model development. Analysis may be limited by censored (e.g.,

nondetects) data for chemical measurements in some media.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.20 0.4 0.50 3 (Region V, AZ, MD) 2

Research Outputs

(1) Development of methodology and demonstration of general test cases

(2) Final outputs: 

•Generation of distributions for exposure model parameters

•Journal article describing improved exposure model parameter values.

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-3.
E-40

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-04. Evaluate Implications of NHEXAS Results for Existing Chronic Exposure

Assessment Methodologies

Short Project

Description:

Screening models (sets of algorithms) are used widely to make preliminary decisions for

Superfund sites, pesticide regulations, and the evaluation of emissions to air and water. 

However, high quality and reliable multimedia monitoring data to validate these models

are virtually nonexistent in the literature, and, as such, the opportunity to test screening

models, even on a qualitative scale, is rarely available. This project will take the dose

estimates from personal monitoring or biomarkers and compare the estimates to those

produced from EPA screening methodologies (also referred to as Tier 1 or initial Tier

assessments). Examples of these methods include recommended exposure models under

the Superfund program and the residential SOPs. 

Goal/Objective: To improve the understanding of the strengths and limitations of existing screening

models and identify opportunities for improving future models.

Significance of

Project:

Screening models provide the basis for preliminary regulatory decisions for pesticides,

hazardous waste sites, and the evaluation of releases to air and water. NHEXAS

databases provide a unique opportunity to evaluate these models.

Suggested

Approach:

This project would be performed in phases,

(1) Determine how the NHEXAS data set would be used (selection of pollutants, interim

findings, activity/dietary patterns, etc.).

(2) Development of the strategy for developing model inputs and relating outputs to the

data set.

(3) Perform the evaluations.

(4) Analyze the results to determine why the models did or did not match with the

survey.

(5) Publish a final report.

A clear methodology should be established for the evaluation procedure that will be

reviewed scientifically. A consistent strategy for dealing with data gaps should be

established.

Data or Input

Needs:

The complete data set (including the data from the questionnaires) should be available

prior to the development of the specific model test sets. Participation from the relevant

EPA program offices is desirable to confirm detail on how screening exposure models

actually are used.

Feasibility

(of analyses with

current NHEXAS

databases):

The project is feasible with the indicated data resources. 

Research Outputs

(1) Development of a modeling strategy that addresses differences in the type of models and how data gaps

will be addressed

(2) Application of screening level and refined multimedia exposure and dose models to selected pollutants 

(3) Evaluation of differences among the results obtained from alternative chronic exposure modeling methods

(4) Final output: Develop final report and journal articles (s).

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-13.
E-41

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-05. Evaluation of Existing Multimedia Models Using the NHEXAS Data Set

Short Project

Description:

High-quality and reliable multimedia monitoring data are virtually nonexistent in the

literature, and, as such, the opportunity to test existing models, even on a qualitative

scale, is rarely available. Several multimedia models have been developed, or are under

development, that predict media concentrations in residential environments based on

inputs such as source characterization and fate and transport, etc. Information available

from the NHEXAS questionnaires, particularly those related to local source

characterization, fate and transport, receptor characterization and activity patterns

(supplemented by default values) should be analyzed and used in these models to

predict media concentrations and personal exposures of the NHEXAS respondents. 

These predictions should be compared with the individual’s exposures and

microenvironmental concentrations monitored in NHEXAS. Examples of models that can

be evaluated include, but are not limited to, TRIM, MEPAS, CARES, LIFELINE, and

CONSEXPO, as well as other linked and nested compartmental models.

Goal/Objective: • To improve the understanding of the strengths and limitations of existing multimedia

models and identify opportunities for improving current and future models.

• Identify the usefulness of the data set and determine how future NHEXAS studies

could better meet the need for testing models.

Significance of

Project:

Multimedia models provide the basis for regulatory decision for pesticides, hazardous

waste sites, and the evaluation of releases to air and water. Currently, there are very

limited opportunities to evaluate these models. NHEXAS provides a unique opportunity

for such evaluations.

Suggested

Approach:

This project would be performed in phases.

(1) Determine how the data set could be used (selection of pollutants, interim findings,

activity/dietary patterns, etc.).

(2) Identification of the models, modeling strategies (e.g., linked and nested multimedia

models) and the development of the strategy for developing model inputs and

relating outputs to the dose measurements in the NHEXAS data set.

(3) Model teams (preferably the developers of each multimedia model) perform the

evaluations.

(4) Analyze the model’s prediction and NHEXAS findings to determine how and why

the models did or did not match with the survey.

(5) Develop recommendations on how future NHEXAS projects could be better

designed to meet the evaluation needs of multimedia modelers.

(6) Publish a final report/peer review publication.

Tasks 1 and 2 could be performed by a panel of exposure assessment experts, through

one or more workshops. Where possible, model owners should be involved in these

workshops. A clear methodology should be established for the evaluation procedures. 

The selected models should be divided into modules, if possible, for estimating

intermediate and final exposure results. Modules should include source characterization,

fate and transport, receptor characteristics, activity patterns, and exposure assessment

(Task 3). A consistent strategy for dealing with data gaps should be established. The

model’s predictions of interim findings (air and surface levels, hand wipe, dietary levels,

activity patterns, etc.) also should be compared to the NHEXAS data set. 

Data or Input

Needs:

The complete data set (including the data from the questionnaires) should be available

prior to the development of the specific model test sets. Models should be well

characterized and model developers should participate in the project. 
E-42

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT M-05

(cont'd)

Feasibility

(of analyses with

current NHEXAS

databases):

The project should be feasible. Only existing models will be evaluated. Where

appropriate, model developers will be included in the project team. Models of many

source terms cannot be included in this exercise because they were not included in

NHEXAS.

Research Outputs

(1) Selection of models for evaluation, development of a modeling strategy that addresses differences in the

type of models and how data gaps will be addressed

(2) Application of selected models to the NHEXAS database

(3) Analysis and comparison of model results to NHEXAS study concentration, exposure, and biomarker

measurements

(4) Improve the development and evaluation of existing multimedia, multipathway exposure models

(5) Final output: Report assessing the findings from the model evaluation study using the NHEXAS database.

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-2.
E-43

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-06. Quantify Uncertainties in NHEXAS Data and Assess Contribution to Model

Errors

Short Project

Description:

Provide uncertainty estimates within the NHEXAS database that is available to

researchers and the public, so that uncertainty is addressed consistently and does not

lead to redundant effort by modelers. Identify how the data uncertainties may impact

modeling uncertainties and illustrate with case studies.

Goal/Objective: • Provide consistent, understandable uncertainty estimates of the NHEXAS data within

the NHEXAS database

• Provide guidance/advice on applicability and use of various types of data in models to

minimize inappropriate model construction.

Significance of

Project:

The NHEXAS database will be used by many researchers and the public. Inclusion of

uncertainty estimates/descriptions will avoid duplication of effort in calculating these

values, will mean that the data uncertainties are treated consistently, and will alert the

public and regulatory community of possible limitations in the use of the data.

Suggested

Approach:

Analytical Measurements

(1) Ensure that NHEXAS data are QA’d and flagged appropriately.

(2) Ensure that NHEXAS data include Limit of Detection information.

(3) Calculate standard errors for each analytical methodology (including sampling and

analysis).

(4) Tag uncertainty data to all NHEXAS data entries and provide a methodology for

error estimation with the public database.

Survey and Time/Activity Information

(1) Provide qualitative assessments of data and their applicability for modeling by

including meta data from field staff on reliability of individual household;

include expert panel judgment of uncertainties of the methodology in general,

including effects of sample size, inaccuracies of recall diaries, observer effects, time

resolution effects, etc.; and

compare survey results from NHEXAS with other data sources.

(2) Include qualitative assessments in database.

Assessment of Model Uncertainties

Convene workshop of modelers to evaluate impacts of uncertainties for variety of

analytes, with differing critical routes of exposure. Provide qualitative descriptions of

uncertainties and caveats for inclusion in the database. Provide case studies to illustrate

how errors impact modeling uncertainties.

Data or Input

Needs:

Paced by the availability of the database, the NHEXAS data need to be quality assured

to flag/remove inappropriate data. Duplicate sample data, split sample data, blanks, and

other QA/QC information on the analytical measurements need to be included in the

database. A description of the sampling and analytical methods also must be included.

Feasibility

(of analyses with

current NHEXAS

databases):

The first part of the effort is quite doable, and should build on normal QA/QC

procedures. This work is to insure that the synopsized uncertainty data also are made

readily available for researchers and the public. The impact on modeling errors is much

more likely to be case dependent, varying with each analyte and model used.
E-44

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT M-06

(cont'd)

Research Outputs

(1) Review NHEXAS databases now under development for data to be included and make sure that QA/QC

data and metadata on QC are in database for both analytical and survey data

(2) Calculate synopsis information from data sets now scheduled to be delivered in FY01

(3) Convene workshop or expert panel to provide qualitative description of uncertainties associated with

survey information

(4) Convene workshop or expert panel to evaluate impact of uncertainties of modeling–prepare case studies for

specific analytes/major routes of exposure

(5) Final output: Incorporate uncertainty estimates and case studies into public database

* NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-4.
E-45

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT

Project Name: M-07. Reconstruct Exposure and Dose Profiles from Biomarker Data Utilizing

Questionnaire and Environmental Measurements

Short Project

Description:

The relationships among environmental measurements, time/activity data, and biomarker

levels will be investigated with the goal of classifying exposure scenarios into steadystate cases (e.g., from long-term average exposures) and intermittent events. There are

several assumptions regarding the route and timing of dose that need to be addressed in

making these estimates, and the questionnaires and time/activity data will be used to

make these determinations. There is the potential to focus on the exposures of children,

in addition to the general population.

Goal/Objective: To develop and evaluate a methodology that provides realistic estimates of the dose

and exposure associated with a biomarker measurement as a function of the types of

exposure that occurred.

Significance of

Project:

Biomarkers can provide an indicator of total absorbed dose. However, making

quantitative estimates of this dose requires several assumptions about the timing and

route of the exposures, as well as the suitability of the model being used. The estimates

of total absorbed dose may help to evaluate current exposure assessment models and

assumptions (e.g., OPP’s Residential SOPs) and to develop and test models describing

residential exposure.

Suggested

Approach:

• The total absorbed dose from a steady-state exposure will be modeled by a massbalance, and the absorbed dose from discrete events will be estimated by an inverted

pharmacokinetic model (in the case of compact classical compartmental models) or

maximum likelihood optimization procedure (in the case of comprehensive

physiologically based models).

• These dose estimates will be linked to a range of possible exposures and

environmental concentrations and then compared with those measured in the

NHEXAS study. Differences will reveal areas of improvement for modeling methods

and indicate additional information that will be useful to collect in future studies.

Data or Input

Needs:

• Pollutant concentrations in solid-food, personal air, dermal rinse, surface press and

wipe, urine (pesticide metabolite), and measurements.

• Pesticide use from household screening, baseline, and follow-up questionnaires.

• Time/activity and food consumption diaries.

• Information on urine volume, creatinine concentration, time of last void, and body

weight.

Feasibility

(of analysis with

current NHEXAS

databases):

This project can be implemented in a 2-year time period assuming the availability of the

NHEXAS database. Likely candidate chemicals are chlorpyrifos, lead, arsenic, and

benzene.

• The food diaries may not be coded to link with ranges of pesticide residues (by food

type), which may limit the temporal resolution of the dietary data estimates.

• There are concerns about applying model parameters (e.g., absorption and elimination

rates) determined in a small number of individuals to the general population because of

differences in personal characteristics such as age, gender, race, and health status.
E-46

EVALUATION/REFINEMENT OF CURRENT EXPOSURE

MODELS AND ASSESSMENTS PROJECT M-07

(cont'd)

Research Outputs

(1) Obtain and merge needed databases 

(2) Analysis of questionnaire/activity data to group by types of exposure

(3) Review metabolite data by individual to identify intermittent and steady-state patterns

(4) Solving and programming the models

(5) Incorporation of the model in an estimation methodology

(6) Uncertainty analysis 

(7) Final output: Journal article on approaches to estimate dose from a biomarker and exposure information 

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-9.
E-47

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-01. Survey and Statistical Aspects of the Design of an Exposure Field Study: 

Lessons Learned from the NHEXAS Pilot Studies

Short Project

Description:

A review, revision, and updating of the discussions, analyses, and conclusions which

provided the original foundation for the NHEXAS design as presented in the Callahan

et al. paper (JEAEE, 1995) will be conducted in light of the NHEXAS pilot studies

experience. The hypothetical calculations would be replaced with calculations based on

actual NHEXAS data. In addition, the analytical and statistical hypotheses that were

generated in the design of the NHEXAS pilots will be reviewed to determine which

hypotheses were testable and which were not.

Goal/Objective: The objective of the project is to provide directly relevant and specific guidance for the

sample and survey design aspects of a national-scale multichemical, multimedia exposure

field study.

Significance of

Project:

The Callahan paper influenced the design of the NHEXAS pilots. Its revision will provide

scientifically relevant, specific, and current guidance for the design of a full national

NHEXAS, and also for other regional or national human exposure field studies, especially

multichemical, multimedia studies.

Suggested

Approach:

Callahan et al. (JEAEE, 1995) discussed the statistical and survey design issues involved in

designing a population-based environmental exposure study. It made a number of design

recommendations – about the optimal selection of Primary and Secondary Sampling Units

(PSUs and SSUs) and households, about screening strategies, about the selection of target

household member, etc. Many of these recommendations were based on calculations of

hypothetical intraclass correlations, design effects, and variances. There is now a wealth

of data available from the three NHEXAS pilot studies that is germane to these survey

design issues. This project would involve a review of the discussions, analyses, and

conclusions in the Callahan paper in light of the NHEXAS experience. The hypothetical

calculations of design effects and intraclass correlations would be replaced with

calculations based on actual data, and the conclusions and recommendations revisited. 

These analyses would be repeated for different pollutants and classes of pollutants to

determine if different conclusions would be reached for different pollutants. In addition,

the analytical and statistical hypotheses that were generated in the design of the NHEXAS

pilots will be reviewed to determine which hypotheses were testable and which were not. 

Testability would be measured through the calculation of the statistical powers of the

tests. Tests with high powers would be deemed testable, whereas tests with low power

would be deemed not testable. Through a review of the data, the reasons for the ultimately

testability will be determined. These calculations will lead to conclusions regarding the

testability of the hypotheses, and the optimal design of future environmental exposure

studies.

Data or Input

Needs:

For each household in each of the three NHEXAS pilots, the following data are needed: 

the PSU and SSU containing the household; the design stratum containing the household;

and the data on each pollutant/medium sampled.

Feasibility

(of analyses with

current NHEXAS

databases):

The current NHEXAS data files have the necessary data to perform the calculations. 

At worst, there are potentially small or empty cells in the survey designs that might force

combining cells or qualifying the conclusions.
E-48

DESIGNING EXPOSURE STUDIES PROJECT DES-01.

(cont'd)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.2 0.5 0.5 1 1

Research Outputs

(1) Gather data sets; plan, review, and approve the statistical analyses

(2) Perform the statistical analyses

(3) Final output: Report with recommendations for the optimal design of a national-scale human exposure study

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project LL-1.
E-49

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-02. Evaluating Modeling Considerations for the Design of Future Exposure Field

Studies

Short Project

Description:

In conducting field studies, usually a study is designed, monitoring data and other

related data are gathered and then statistical analyses performed to interpret the data. 

However, from a model development, model application, or model evaluation

perspective, the data gathered may be insufficient, particularly for inferential purposes. 

Future NHEXAS studies should accommodate the needs of existing or modified

multimedia models. To achieve this, the model parameters should be understood and

incorporated in the study design. Sample parameters include those related to

time/activity patterns, contact rates, and dermal and dietary exposure (e.g., surface

coverings in residences, contact times with these surfaces).

Goal/Objective: To establish a procedure wherein modeling considerations are accommodated in the

early stages of the design of future NHEXAS studies.

Significance of

Project:

The power of any future NHEXAS study lies in interpreting the measurement results

within the risk assessment/risk management paradigm used by EPA to select actions

designed to protect the public. This interpretation can be done effectively only through

modeling the exposures and the changes resulting from the risk management actions. It

is critical that future NHEXAS field studies incorporate modeling considerations in their

design from the very inception to ensure their usefulness for protecting human health

and the environment.

Suggested

Approach:

The results of the NHEXAS pilot studies can be used to identify a multimedia exposure

assessment methodology, either currently implemented in a model or that can be later 

modified. This methodology can be used to establish the parameters to be monitored in

future studies.

Data or Input

Needs:

All available data from NHEXAS pilot studies.

Feasibility

(of analyses with

current NHEXAS

databases):

This project is immediately feasible and should be undertaken early in the design

process for any future NHEXAS or large-scale field study.

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.3 0.3 0 1 1

Research Outputs

(1) Determine model parameters to be monitored

(2) Final output: Demonstrate use of poststudy data

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project M-5.
E-50

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-03. Scaling Up: Evaluation of the NHEXAS Pilot Fixed Costs, Coordination and

Communication Strategies, and Degree of Standardization

Short Project

Description:

This project evaluates the NHEXAS pilot start-up expenditures and cost implications for

various scales of coverage. The evaluation also will address the effectiveness of

coordination approaches that were used and their application to a full scale survey, and

communication approaches as results were shared with respondents and with local,

state, and federal officials and organizations. A key component of the analysis will be

the evaluation of approaches that were standardized explicitly and a determination of

whether or not the degree of standardization was adequate.

Goal/Objective: This project will transfer the experience of the pilots to compare and contrast the

implementation and communication strategies of the three consortia to determine which

strategies or components worked well and which components need improvement and

standardization for the most cost-efficient full survey possible.

Significance of

Project:

A national-scale survey must utilize the most cost-effective approaches. Experiences

gained coordinating and standardizing implementation procedures for the pilots provide

valuable information for the design of future large-scale projects. Communication is a

component of human exposure assessment that often is given low priority by project

planners and sponsors, yet it is an important component of the overall package of

benefits that are provided to the respondents and that serves as a significant

component of the incentives used to promote participation. In addition, timely reporting

of values that exceed nominal thresholds is a mandatory component of all human

exposure research.

Suggested

Approach:

(1) Interviews will be conducted and pilot documentation collected addressing

coordination, communication, and degree of standardization of management and

staff from the involved agencies and consortia.

(2) Cost information will be collected.

(3) The processes used in the three pilot studies to share individual results with the

respondents will be reviewed and compared. The respondents may be interviewed

to determine how well they understood what was provided and what questions were

not answered. In a focus group setting, the same data information using each of the

three study processes will be tested to allow direct comparison of approaches and

determine the best means of sharing data.

(4) Interviews with the local and state agencies that received notification from any of

the three studies for measured values exceeding state or local reporting thresholds

will be held. The process by which the data were shared, what each agency did after

receiving the data, and the range of thresholds reported by the states, and their role

in release of data and dissemination of results will be reviewed.

(5) The reporting mechanisms for the three studies will be reviewed for common

approaches. The utility of the reports will be assessed. Attempts will be made to

determine what means of data reporting are of value to different levels of users, and

to develop a basic format to be used in reporting composite data to subjects.

(6) Recommendations will be made for an optimum scale-up strategy and a

communication evaluation manual will be developed.

Data or Input

Needs:

Cost data; available documentation; NHEXAS database; copies of material used by each

member of the consortium to provide results to the respondents and data to local, state,

and federal agencies
E-51

Feasibility

(of analyses with

current NHEXAS

databases):

Feasible; all information ultimately available. Communications assessment may proceed

immediately without access to the NHEXAS database. Recontacting participants and

state and local representatives may be problematic.
E-52

DESIGNING EXPOSURE STUDIES PROJECT DES-03

(cont'd)

Estimated Level-of-Effort

Staff Time/Year

PI Scientist Support No. Tasks/Year No. Years

0.4 0.5 1.5 1 1

Research Outputs

(1) Collect needed data and compare NHEXAS processes

(2) Complete local/state interviews

(3) Final outputs: Report recommending approaches for effective communication. Report recommending

optimum scale-up strategy

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects LL-9 and LL-12.
E-53

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-04. Influence of Incentives, Response Rates, and Nonresponse Bias on Survey Design

Short Project

Description:

Analysis of NHEXAS recruitment procedures and incentives and their effects on response

rates for various subpopulations will be conducted. Analysis of potential bias resulting from

NHEXAS nonresponse based on information obtained from the descriptive questionnaire,

and information/observations recorded by interviewers on noncontacts or nonrespondents

for each study and for various subpopulations are important elements in the design of future

studies.

Goal/Objective: Determine the recruitment procedures and incentives that should be recommended for a

national NHEXAS or other large field study. Determine the extent of nonresponse bias that

can be expected at each stage of these studies.

Significance of

Project:

Projected participant incentives and response rates will be a major consideration for OMB

approval of a national NHEXAS. It will be necessary to project reasonably high response

rates and to justify the incentives and procedures proposed to achieve those response rates.

Suggested

Approach:

Contrast recruitment strategies, information provided to potential respondents, incentives,

and response rates across (and within, where feasible) the NHEXAS pilot studies for

subpopulations of interest. Compare recruitment procedures, incentives, and response rates

with those from other studies collecting comparable data (e.g., TEAM and NHANES). Use

the NHEXAS Descriptive Questionnaire data to compare characteristics or respondents and

nonrespondents for each NHEXAS pilot study, stage of participation, and subpopulations

of interest (e.g., race/ethnicity, gender, urbanicity).

Data or Input

Needs:

Indicators from each NHEXAS pilot study of participation for each stage of the study:

households contacted (no answer/refusals/number of contacts), descriptive questionnaire,

baseline questionnaire, core monitoring, and sampling for each matrix and pollutant.

Documentation of the recruitment procedures (including information provided, informed

consent, approaches used for questionnaires and sampling, communications and contacts

with press/community, etc.) and incentives used by each NHEXAS pilot study.

NHEXAS descriptive questionnaire data.

Incentives, recruitment procedures, and response rates for other studies collecting

comparable data (e.g., TEAM and NHANES)

Quality Systems Implementation Plans, protocols for survey sampling and training manuals

for survey teams

Feasibility

(of analyses with

current NHEXAS

databases):

Must complete QC on descriptive questionnaire data for each NHEXAS consortium.

Must complete NHEXAS chemical analyses, set respondent flags, and QC those flags.

Must document all NHEXAS respondent selection procedures for each stage of each study.

Research Outputs

(1) Secure necessary data; QA data

(2) Final output: Impact of response rates on survey design

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects LL-5 and A-11.
E-54

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-05. Cost-Effectiveness of Exposure Measures and Comparisons to Indirect

Methods

Short Project

Description:

This project evaluates the cost-effectiveness of exposure measures for pollutants and

pathways using decision analysis, value of information, and cost-benefit analysis

techniques. Data from NHEXAS pilot studies questionnaires, environmental sampling,

personal sampling, and biomarkers will be analyzed to assess the reproducibility,

accuracy, limits of detection (LODs), ranges, interferences, uncertainty, and costs, for

the purpose of evaluating direct measures relative to indirect methods based on existing

data and models. From the analysis, identify methods that were unsuccessful and other

methods (i.e., questionnaires, simplified or indirect sampling schemes) that could serve

as screening tools in large-scale exposure studies to classify more highly exposed

individuals and reduce costs.

Goal/Objective: (1) Compare the costs and benefits of methods used to characterize multimedia

exposures and examine their implications on sample size needs, sampling costs and

burdens to the study subjects;

(2) Evaluate the utility of low-cost screening methods for identifying households or

subjects requiring more intensive monitoring and for providing data useful for

exposure assessment (e.g., distributions).

(3) Assess the cost and uncertainty differences among exposure models using

screening level measurements, questionnaire information, nonprobability samples

(i.e., purposive samples), and existing exposure-related data relative to the NHEXAS

measurements and study designs. 

Significance of

Project:

Multimedia, multipathway studies are expensive to implement. Screening methods are

needed to provide a low-cost approach that can identify highly exposed individuals and

identifying which samples or media should be analyzed. In addition, screening methods

with sufficient quantitative power may provide data adequate for exposure analysis and

modeling. This study will identify the incremental differences in model performance

associated with more detailed (sensitive and accurate) methods, and with representative

population samples–relative to more focused stratified or specialized substudies. This

study will provide information on how to minimize costs and prioritize resource

allocations for the design of future NHEXAS and other large-scale exposure studies. 

Suggested

Approach:

(1) Identify screening methods, or methods and questionnaire data that could be used

for screening, from the NHEXAS pilot studies and assess the ranges,

reproducibility, accuracy (i.e., false positives/false negatives) and LODS for

identified screening methods with more rigorous and expensive methods.

(2) Determine which methods were successful (or could be successful) and those that

were not.

(3) Assess the cost and burden (participant and field staff) of methods used in the

NHEXAS pilot studies and developed more recently, that show promise for use in

future studies.

(4) Compare exposure models derived from measurement with different sensitivities

(e.g., questionnaires and screening measures with differences in analytical

performance) with models using subject-specific chemical measurements,

characteristics, and activities.

(5) Develop methods selection criteria.
E-55

DESIGNING EXPOSURE STUDIES PROJECT DES-05

(cont'd)

Data or Input

Needs:

(1) A listing of field and analysis methods with performance data used by each

NHEXAS pilot study 

(2) Concentration, biomarker, questionnaire, and time/activity data 

(3) Information about the time and effort needed to implement each field collection or

measurement method and any associated laboratory and analysis costs, particularly

for paired low-cost/high-cost methods at homes where both were employed.

(4) Exposure and intake models from each study

Feasibility

(of analyses with

current NHEXAS

databases):

High, there are sufficient data groups to allow the proposed analysis. Some examples

include, for VOCs, photoionization detector, and passive diffusion badges versus

actively pumped sorbent tubes; for pesticides, immunoassay methods and analyses by

gas chromatography with various detectors; for metals, XRF versus inductively coupled

plasma (ICP) with various detectors, AES, and ICP/MS; for PAHs in air, real-time PAH

monitor. Limitations include equivalency in terms of temporal and geographic variability,

SES/demographic/population variability/representativeness, collection and analytical

methods.

Research Outputs

(1) Compile listings of methodology and associated data (QC, range, LOD) from databases; obtain cost

information and models from each NHEXAS study for comparisons 

(2) Generate statistical comparison data sets of paired sample results, assessment of success and cost of

potential screening methods

(3) Final outputs: Final reports and peer reviewed publications describing screening method assessment

results, methods selection criteria, and model performance 

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Projects LL-6, LL-8, EA-08,

and A-11.
E-56

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-06. Optimizing NHEXAS Pilot Information and Methods To Move to a NationalScale Exposure Field Study

Short Project

Description:

A thorough evaluation will be performed of single- and multimedia pollutant issues and

regulatory initiatives for the purpose of contributing to the design of a national-scale

exposure field study. The information obtained in the pilot studies and other source

and effects information will be utilized to prioritize the selection of pollutants and

pathways leading to exposure. Included would be an evaluation of the ability of each

consortium to achieve the objectives or hypotheses originally proposed for each type

of investigation. This project will capture and integrate the knowledge gleaned from the

analysis, interpretation, and evaluation of the experiences in undertaking the NHEXAS

pilot studies for assisting in designing and planning the next generation of NHEXAStype or other major field studies. 

Goal/Objective: (1) To compile the results and conclusions from the analyses conducted by the

NHEXAS studies and evaluate the successes and failures in achieving the original

hypotheses;

(2) To document the successes and shortcomings of the NHEXAS pilot studies based

on the outcomes of implementing the Strategic Analysis Plan;

(3) To build a knowledge base on the current and emerging scientific and regulatory

issues associated with pollutants and their occurrence in multimedia;

(4) To build a knowledge base on the prevalence of xenobiotics measured in biological

samples from human populations;

(6) To develop strategies for optimizing exposure information that permit effective

management and reduction programs;

(7) To link the above information to support moving forward, as part of the input to the

design of the national-scale exposure field study. 

Significance of

Project:

The products and outcome of this effort provide justification and a defensible scientific

basis to design and implement a national-scale exposure field study. 

Suggested

Approach:

(1) Obtain completed significant analyses on the databases and information content

obtained by each consortium and from the implementation of the Strategic Analysis

Plan.

(2) Utilize a multidisciplinary team to conduct an overall evaluation of the NHEXAS

pilot studies;

(3) Identify a team of scientists to work with the program offices, other government

agencies, states, and other stakeholders to acquire the knowledge base for

selecting and prioritizing pollutants and pathways and for identifying innovative

exposure reduction strategies.

(4) Evaluate the success and completeness of the above in workshops composed of

EPA and extramural scientists, other professionals, partners and stakeholders. 

Incorporate the output from the workshops to refine and augment the knowledge

base to be used for designing the national-scale exposure field study. 

Data or Input

Needs:

The analyses conducted to achieve each study’s hypotheses and objectives and the

results from the implementation of the Strategic Analysis Plan. The project initiation is

contingent on having sufficiently completed products from other projects in the

Strategic Analysis Plan. Information is obtained from the analyses conducted, program

office activities and initiatives, NHANES, other exposure and health-related studies

(e.g., EPA/ORD STAR Grant Program, NIEHS, National Cancer Institute, Health Effects

Institute, National Institute for Occupational Safety and Health, ATSDR), and state

exposure data and pollution reduction initiatives.
E-57

DESIGNING EXPOSURE STUDIES PROJECT DES-06

(cont'd)

Feasibility

(of analyses with

current NHEXAS

databases):

High, if the Strategic Analysis Plan is implemented in a timely manner, including the

projects analyzing and documenting the lessons learned. 

Research Outputs

(1) Evaluate information and summarize findings

(2) Identify strategies and conduct workshops

(3) Final outputs: Synthesis of information and transferring output to support moving to future large-scale

exposure field studies

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project LL-3 and LL-4.
E-58

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-07. Cross-Studies Evaluation and Recommendations for Standardization of Data

Management Procedures in Large-Scale Exposure Field Studies

Short Project

Description:

This project will analyze the data collection and automated survey management

procedures developed for each NHEXAS pilot study from sampling, through sample

analysis and to inclusion in the final database. The data QA/QC procedures and QC

data will be evaluated, and the resulting database structures will be examined. The

strengths and weaknesses of the three approaches will be noted with respect to ongoing

EPA data management initiatives. NHEXAS pilot QC data will be analyzed, and

recommendations for future studies will be developed. These recommendations will

include areas that would benefit from standardization; for example, data transfer from

analytical laboratories, database elements, QA/QC codes, information shells, etc.

Goal/Objective: To have appropriate conventions and procedures for recording data and data quality

and to increase the efficiency of future data collection efforts.

Significance of

Project:

Management of large EPA databases as a valued resource is currently a high priority

within EPA. Procedures and conventions used to manage the integrity of data are

evolving but are essential to both primary and secondary data users. The NHEXAS

studies are an excellent opportunity to analyze the procedures used by three different

organizations to develop and populate study databases. Results of this project will be

used for improving/optimizing data collection and storage for future human exposure

studies and other EPA primary data collection efforts.

Suggested

Approach:

(1) Assess the data management processes and conventions used in each NHEXAS

pilot study.

(2) Review the status of EPA efforts with respect to Reinventing Environmental

Information (REI), specifically, current status of data standards (Chemical ID,

Location ID, etc.), the Environmental Data Registry (EDR), the Environmental

Information Management System (EIMS) and any other relevant efforts to insure the

quality and accessability of EPA databases.

(3) With stakeholder input (EPA program offices, involved Federal agencies, etc.),

recommend application of EPA conventions and procedures for a future nationalscale NHEXAS or other large exposure field database. Recommend conventions in

areas where none exist. Conventions that document the limitations of the data are

particularly important. 

(4) Analyze available quality control information (i.e., batch level laboratory QC

information) and develop Data Quality Indicators that can be stored with the data for

the benefit of data users.

Data or Input

Needs:

Needed information for each consortium: data management plan/procedures; field data

collection procedures; procedures for transferring the field, analytical,

questionnaire/diary and related data into the final databases; data QA/QC procedures;

and final database design. Each consortium also will need to provide an analysis of how

well their procedures worked and problems encountered.

Feasibility

(of analyses with

current NHEXAS

databases):

Data collection and processing SOPs are available from each consortium. The analysis

of how well the procedures worked in each consortium will need to be done in the

relatively near future, while the staff involved are still available. EPA-level initiatives in

this area are active and ongoing.

Research Outputs

(1) Collect and review NHEXAS SOPs and QA documentation

(2) Final output: A data management strategic plan for future exposure studies

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project LL-13.
E-59

DESIGNING EXPOSURE STUDIES PROJECT

Project Name: DES-08. Evaluation of NHEXAS Results To Derive an Optimal Set of QA/QC Activities

for Human Exposure Field Studies

Short Project

Description:

This project will identify and evaluate the QA/QC across laboratories and consortia. 

This will include an analysis of the NIST and comparability study data. The project will

develop an annotated inventory of recommended QA/QC activities needed to

successfully conduct large-scale human exposure measurement studies. This will

include all phases of the study from planning to final database development.

Goal/Objective: The goal of this project is to provide an optimum set of QA/QC activities for future

human exposure studies. This is needed to assure that the studies produce data of the

required quality while keeping costs to a minimum.

Significance of

Project:

Effective QA/QC is essential to produce high-quality data from the funds invested in

any field exposure study. Because of the high cost of these types of studies, it is also

important not to include unnecessary QA/QC that might increase costs. By examining

the QA/QC used in the NHEXAS studies, guidance can be developed for this critical

study component.

Suggested

Approach:

(1) Identify the QA/QC activities performed by each consortium and laboratory,

including the NIST standards and performance evaluations studies, the

interlaboratory comparability study, QA documentation, reviews, audit reports,

reviews of field performance, and QA samples.

(2) Evaluate the success of each activity and the benefits it provided to the study.

(3) Identify areas where data quality could have been improved with additional QA/QC

activities or areas where excess QA/QC activities might have been employed.

(4) Develop an annotated inventory of the recommended QA/QC activities needed to

conduct a large-scale human exposure study.

Data or Input 

Needs:

Access is needed to the complete NHEXAS database and documentation, including all

QA/QC information of each consortium and laboratory and the NIST and comparability

study results and reports.

Feasibility

(of analyses with

current NHEXAS

databases):

The study is feasible using data from the NHEXAS database. A mixture of laboratory,

field and QA expertise is needed to evaluate information.

Research Outputs

(1) Review consortia documents

(2) Final outputs:

•Consolidate information from documents and develop annotated inventory

•Guidance document on optimal QA/QC for human exposure field studies

NOTE: Crosswalk to NHEXAS Data Analysis Workshop (EPA 600/R-99/077, 1999) Project LL-10.