EPA 

PB93-963510 

OSWER #9285.7-15-1 

February 1994 

GUIDANCE MANUAL FOR THE 


IEUBK MODEL FOR LEAD IN CHILDREN 


Office of Solid Waste and Emergency Response 

U.S. Environmental Protection Agency 

Washington, DC 20460 
NOTICE 

This document provides guidance to EPA staff. It also provides guidance to the public and to the 

regulated community on how EPA intends to exercise its discretion in implementing the National 

Contingency Plan. The guidance is designed to implement national policy on these issues. The 

document does not, however, substitute for EPA's statutes or regulations, nor is it a regulation 

itself. Thus, it cannot impose legally-binding requirements on EPA, States, or the regulated 

community, and may not apply to a particular situation based upon the circumstances. EPA may 

change this guidance in the future, as appropriate. 
U.S. ENVIRONMENTAL PROTECTION AGENCY 

TECHNICAL REVIEW WORKGROUP FOR LEAD 

The Technical Review Workgroup for Lead (TRW) is an interoffice workgroup convened by the 

U.S. EPA Office of Solid Waste and Emergency Response/Office of Emergency and Remedial 

Response (OSWER/OERR). 

Region 8 

Susan Griffin 

Denver, CO 

Region 2 

Mark Maddaloni 

New York, NY 

Region 3 

Roy Smith 

Philadelphia, PA 

Region 5 

Patricia VanLeeuwen 

Chicago, IL 

Region 8 

Chris Weis 

Denver, CO 

NCEA/Washington 

Karen Hogan 

CHAIRPERSON 

MEMBERS 

NCEA/Washington 

Paul White 

NCEA/Cincinnati 

Harlal Choudhury 

NCEA/Research Triangle Park 

Robert Elias 

NCEA/Research Triangle Park 

Allan Marcus 

ORD/Washington 

Barbara Davis 
GUIDANCE MANUAL FOR
 

THE INTEGRATED EXPOSURE UPTAKE BIOKINETIC
 

MODEL FOR LEAD IN CHILDREN
 

Prepared by
 

THE TECHNICAL REVIEW WORKGROUP FOR LEAD
 

for
 

THE OFFICE OF EMERGENCY AND REMEDIAL RESPONSE
 

U.S. ENVIRONMENTAL PROTECTION AGENCY
 

with Document Production Assistance from
 

THE ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
 

U.S. ENVIRONMENTAL PROTECTION AGENCY
 

RESEARCH TRIANGLE PARK, NC 27711
 
PREFACE 

The Guidance Manual has been developed to assist the user in providing appropriate 

input to the Integrated Exposure Uptake Biokinetic (IEUBK) Model for Lead. The IEUBK 

Model is designed to model exposure from lead in air, water, soil, dust, diet, and paint and 

other sources with pharmacokinetic modeling to predict blood lead levels in children 6 

months to 7 years old. This manual emphasizes the use of the IEUBK Model for estimating 

risks from childhood lead exposure to soil and household dust that might be encountered at 

CERCLA/RCRA sites, although other applications of the model are possible. The manual 

provides background information on environmental exposure parameters and recommends 

some useful approaches that allow flexibility for site-specific risk assessments, where 

possible. Default parameters are recommended unless there is sufficient data to characterize 

site-specific conditions. A separate Appendix on sampling is being developed and will be 

issued later. A Technical Support Document details the basis for the biokinetic parameters 

and equations in the IEUBK Model. In addition, EPA is continuing to compare the results of 

field studies with model predictions and will release these findings in a later document. 

One of the proposed uses of this model will be support for the implementation of an 

Interim Directive of the Office of Solid Waste and Emergency Response (OSWER). This 

Interim Directive explains how the IEUBK Model results can be a tool for the determination 

of site-specific cleanup levels. In this context, the model is viewed as a predictive tool for 

estimating changes in blood concentrations as exposures are modified. The model is also 

viewed as a useful tool that should aid the Agency in making more informed choices about 

the concentrations of lead that might be expected to impact human health. 

The development of the model has included the cooperative efforts of several EPA 

programs over nearly a decade. For the last three years, these efforts have been coordinated 

by the Technical Review Workgroup for Lead. During its development, the model has 

undergone review by outside scientists, and its usefulness has been evaluated by EPA staff, 

contractors, and other reviewers assessing site-specific risk. The current version of the 

IEUBK model and the Guidance Manual incorporates many of their recommendations. 

The use of mathematical and statistical models for environmental risk assessment has 

become increasingly widespread because of the many practical difficulties encountered in 

controlling human exposure to toxicants with subtle and long-lasting effects. Exposure to 

lead during infancy and childhood increases the risk of irreversible neurobehavioral deficits at 

ii 
levels of internal exposure as low as 10 to 15 μg Pb per 100 mL of blood (10 to 15 μg/dL). 

Lead has many known sources, and many pathways from its environmental sources into the 

child's body (U.S. Environmental Protection Agency, 1986). The Environmental Protection 

Agency has long been interested in methods for relating environmental lead concentrations to 

blood lead concentrations in children. Earlier approaches based on statistical correlations 

provided essential information on the existence and magnitude of childhood lead uptake from 

persistent exposure to different environmental sources, including lead in air, diet, drinking 

water, soil, dust, and lead-based paint. Unfortunately, these statistical relationships are 

limited in their ability to estimate the effects of alternative lead abatement methods that 

change pathways as well as sources. 

In 1985 the EPA Office of Air Quality Planning and Standards began to develop an 

alternative approach for estimating the effectiveness of alternative National Ambient Air 

Quality Standards for lead, particularly around point sources of air lead emissions such as 

smelters. This was a computer simulation model with two components: (1) a model of the 

biokinetics of lead distribution and elimination whose parameters vary with the child's age, 

and (2) a multi-source and multi-media lead exposure model in which air lead concentrations 

change over time. The biokinetic model was based on studies at New York University by 

Naomi Harley, Theodore Kneip, and Peter Mallon. The U.S. Environmental Protection 

Agency Clean Air Science Advisory Committee (CASAC) reviewed and found acceptable the 

OAQPS staff report documenting the model in 1989. A subsequent OAQPS staff paper 

reviewing the National Ambient Air Quality Standard for Lead, which included results of 

applying the model to point sources of air lead such as smelters and battery plants, was also 

evaluated by CASAC in 1990 (U.S. Environmental Protection Agency, 1990B). 

Those who had been involved in developing the lead model then received a large and 

growing number of requests on applications of the model in a wide variety of other contexts 

not originally intended for model use. The largest number of these requests involved the use 

of the model to estimate the effects of soil lead abatement at Superfund sites. 

The air model was further developed to include enhancements in absorption and 

biokinetics. In November, 1991, the Indoor Air Quality and Total Human Exposure 

Committee (IAQTHEC) of EPA's Science Advisory Board (SAB) reviewed the Uptake 

Biokinetic Model for Lead (version 0.4) and evaluated its use in assessing total lead 

exposures and in aiding in developing soil cleanup levels at residential CERCLA/RCRA 

sites. The Committee's Report was transmitted to EPA Administrator William K. Reilly in 

iii 
March, 1992. The Committee concluded that while refinements in the detailed specifications 

of the model would be needed, the approach followed in developing the model is sound. The 

Committee stated that the model can effectively be applied for many current needs even as it 

continues to undergo refinement for other applications, based upon experience gained in its 

use. 

The Committee was concerned that the reliability of the results obtained using the 

model is very much dependent on the selection of the various coefficients and default values 

that were used. In particular, the Committee identified the need for guidance on the "proper" 

geometric standard deviation (GSD) and the use of default values for other parameters. In 

addition to these general comments, specific comments were included in the Report. The 

comments of the SAB and other reviewers have been considered in this revision of the 

Guidance Manual. 

Since the SAB review, EPA has further refined the model. The four main components 

of the current IEUBK model are: (1) an exposure model that relates environmental lead 

concentrations to age-dependent intake of lead into the gastrointestinal tract; (2) an absorption 

model that relates lead intake into the gastrointestinal tract and lead uptake into the blood; (3) 

a biokinetic model that relates lead uptake in the blood to the concentrations of lead in several 

organ and tissue compartments; and (4) a model for uncertainty in exposure and for 

population variability in absorption and biokinetics. A Technical Support Document that 

details the selection of parameters and equations in the model is available. 

As with any multicompartmental model, pools in the compartmental analysis can be 

identified with specific organs or organ systems only if biological concentrations of the 

compartments are known. For some compartments, the biological concentrations have been 

measured at a number of time points so that the movement of lead from one compartment to 

another can be estimated. The biokinetic and absorption components of the model, however, 

are not observed directly but are inferred from accessible data. 

In developing the IEUBK Model, EPA has learned much from "real world" 

comparisons of blood lead and predicted values—not only that the model works, but also that 

it can be made to work better. Guidance on the appropriate use of the model is based on our 

experiences, where possible, and on the experiences of many users and reviewers of the 

model. Many of the most useful parts of the Guidance Manual have been suggested by these 

reviewers. 

iv 
While the model has been used to support the NAAQS for Lead, the Clean Water Act 

national regulations, and several other regulatory and enforcement issues, EPA is continuing 

its validation of the IEUBK Model with detailed evaluation of additional data collected from 

different types of sites. Comparison of predicted and empirical blood lead concentrations will 

be described in the Field Study Data Set Comparisons Document described in Section 1.2.2. 

Although EPA is releasing version 0.99d of the IEUBK Model to ensure consistent 

application among users, the Agency will continue to evaluate the results of validation 

exercises and different applications of the model. The Environmental Protection Agency will 

determine periodically whether refinements to the model are warranted, considering scientific 

advancements and the development of alternative approaches. 

The Environmental Protection Agency welcomes the suggestions of those using the 

IEUBK model. Questions regarding the site-specific application of the IEUBK Model should 

be raised with the appropriate Regional Toxics Integration Coordinator. Comments on the 

technical content of the manual or suggestions for its improvement may be brought to the 

attention of the Technical Review Workgroup for Lead, whose current addresses are listed on 

page xxi. 

v 
TABLE OF CONTENTS
 

Page 

PREFACE ............................................. ii 


 

LIST OF TABLES ....................................... xii
 

LIST OF FIGURES ....................................... xvi
 

LIST OF SCREENS ...................................... xviii
 

TECHNICAL REVIEW WORKGROUP FOR LEAD ................. xx
 

GLOSSARY OF MODEL TERMS ............................. xxii 

1. BEFORE YOU START ................................. 1-1
 

1.1	 BACKGROUND: PURPOSE AND DEVELOPMENT OF 
 

THE MODEL .................................. 1-1
 

1.1.1 Description of the Model ..................... 1-1
 

1.1.2 Simulation of Childhood Lead Exposure and 
 

Retention ................................ 1-3
 

1.1.3 Historical Evolution from Slope Factor Models to the 
 

Integrated Exposure Uptake Biokinetic Model ........ 1-5
 

1.1.4 Using the Integrated Exposure Uptake Biokinetic 
 

Model for Risk Estimation .................... 1-9
 

1.1.5	 Validation of the Integrated Exposure Uptake 
 

Biokinetic Model .......................... 1-10
 

1.1.5.1 The Model Is Biologically and Physically 
 

Plausible .......................... 1-11
 

1.1.5.2 The Model Is Computationally Accurate ..... 1-12
 

1.1.5.3 Emphirical Comparisons of the Model ....... 1-12
 

1.2 ORGANIZATION OF THE MANUAL .................. 1-13
 

1.2.1 Increasing Levels of Guidance and 
 

Technical Assistance ........................ 1-13
 

1.2.2 Additional Documentation .................... 1-14
 

1.3	 GETTING READY TO USE THE MODEL ............... 1-15
 

1.3.1 Preparing a Site-Specific-Exposure Scenario ......... 1-15
 

1.3.2 Understanding How the Biokinetic Component of the 
 

Model Works ............................. 1-17
 

1.3.3 Understanding Limitations of the Model ........... 1-18
 

1.4	 RUNNING THE MODEL .......................... 1-19
 

1.4.1 Your Responsibilities ........................ 1-19
 

1.4.2 Exploring Model Options ..................... 1-20
 

1.4.3 Documentation of Input Parameter and Data Files ..... 1-21
 

1.4.4 Documentation of Model Output ................ 1-22
 

1.4.4.1 Selecting Output Alternatives ............. 1-22
 

1.4.4.2 Understanding the Output ............... 1-23
 

1.4.4.3 Interpreting the Output and Communicating 
 

the Results ......................... 1-24
 

1.5 REFINEMENTS AND ENHANCEMENTS ............... 1-28
 

1.6 GETTING MORE HELP ........................... 1-29
 

vi 
TABLE OF CONTENTS (cont'd) 

Page 

2. A GUIDED TOUR THROUGH THE LEAD MODEL ............. 
 

2.1 THE LEAD MODEL IS DRIVEN BY MENUS ............ 
 

2.2 DETAILED DESCRIPTION OF MENUS ................ 
 

2.2.1 Help Menu .............................. 
 

2.2.1.1 General Help ....................... 
 

2.2.1.2 Information Menu .................... 
 

2.2.1.3 Other On-Line Help Menus .............. 
 

2.2.2 Parameter Input Menus ...................... 
 

2.2.2.1 Air Lead .......................... 
 

2.2.2.2 Dietary Lead ....................... 
 

2.2.2.3 Drinking Water Lead .................. 
 

2.2.2.4 Soil and Dust Lead ................... 
 

2.2.2.5 Alternate Source ..................... 
 

2.2.2.6 Bioavailability of Lead in Food, Drinking
 

Water, Soil, and Dust ................. 
 

2.2.2.7 Maternal-Fetal Lead Exposure ............ 
 

2.2.2.8 Save and Load Options ................. 
 

2.2.3 Computation Menu ......................... 
 

2.2.3.1
 

2.2.3.2
 

2.2.3.3 

2.2.3.4 

2.2.3.5 

Run a Single Simulation of the Model ....... 
 

Run Multiple Simulations of the Model for
 

a Range of Media Lead ................. 
 

Multiple Simulation Runs of a Medium To
 

Find Concentration of Lead in the Medium 
 

That Produces a Specified Blood Lead ....... 
 

Batch Mode Multiple Simulation Runs
 

Using Input Data Files ................. 
 

Statistical Analyses of Batch Mode
 

Data Sets .......................... 
 

2.3 BUILDING AN EXPOSURE SCENARIO ................ 
 

2.3.1 Air Lead Menu ............................ 
 

2.3.1.1 Default Air Lead Exposure Parameters ...... 
 

2.3.1.2 Ventilation Rate ..................... 
 

2.3.1.3 Indoor/Outdoor Activity Patterns .......... 
 

2.3.1.4 Lung Absorption ..................... 
 

2.3.2 Dietary Lead Menu ......................... 
 

2.3.2.1 Total Dietary Lead Exposure ............. 
 

2.3.2.2 Dietary Lead Exposure by Additional
 

Pathways .......................... 
 

2.3.3 Drinking Water Lead Exposure Menu ............. 
 

2.3.3.1 Drinking Water Lead Default Exposure 
 

Parameters ......................... 
 

2.3.3.2 Alternate Drinking Water Exposure by Age ... 
 

2.3.4 Soil/Dust Lead Exposure Menu ................. 
 

2-1 

2-1 

2-3 

2-3 

2-3 

2-4 

2-4 

2-4 

2-4 

2-7 

2-8 

2-10 

2-14 

2-17 

2-17 

2-18 

2-20 

2-20 

2-20 

2-21 

2-22 

2-26 

2-27 

2-27 

2-27 

2-27 

2-28 

2-29 

2-29 

2-29 

2-31 

2-33 

2-33 

2-36 

2-37 

vii 
TABLE OF CONTENTS (cont'd) 

Page 

2.3.4.1 Soil and Dust Lead Default Exposure 

Parameters ......................... 
 

2.3.4.2 Exposure to Soil and Dust ............... 
 

2.3.4.3 Sources of Dust Exposure ............... 
 

2.3.4.4 Fraction of Exposure as Soil or Dust ........ 
 

2.3.4.5 Bioavailability of Lead in Soil and Dust ...... 
 

2.3.5 Alternate Source Exposure Menu ................ 
 

2.4	 STARTING AND RUNNING THE MODEL .............. 
 

2.4.1 Loading and Starting the Model ................. 
 

2.4.2 Running the Model ......................... 
 

2.4.2.1 Computation Options .................. 
 

2.4.2.2 Output Options ...................... 
 

3.	 QUICK REFERENCE FOR THE EXPERIENCED USER .......... 
 

3.1 FINDING YOUR WAY THROUGH THE MENUS .......... 
 

3.2 PARAMETER LIST WITH DEFAULT VALUES ........... 
 

3.3 BATCH MODE INPUT FORMAT ..................... 
 

3.4 OUTPUTS FOR DOCUMENTATION, BRIEFING, AND
 

PRESENTATION ................................ 
 

3.4.1	 Overview of Output Options ................... 
 

3.4.1.1 Plotting ........................... 
 

3.4.1.2 Uses of Batch Mode Analysis ............ 
 

3.4.2 Detailed Instructions on Output Options ............ 
 

3.4.2.1
 

3.4.2.2
 

3.4.2.3 

3.4.2.4
 

3.4.2.5
 

3.4.2.6
 

3.4.2.7
 

Save Output from a Single Run ........... 
 

Save Output from Multiple Runs for 
 

Probability Plots ..................... 
 

Save Output from Multiple Runs for 
 

Media-Level Plots .................... 
 

Save Output from a Batch Mode Run ........ 
 

Probability Plots for Single Runs .......... 
 

Probability Plots for Multiple Runs ......... 
 

Multi-Level Plots for Blood Lead Versus 
 

Media Lead ........................ 
 

3.4.3	 Recommendations on Multi-Level Soil Lead 
 

Exposure Scenarios ......................... 
 

4. MORE ABOUT THE MODEL ............................ 
 

4.1	 LEAD BIOAVAILABILITY ......................... 
 

4.1.1 Background .............................. 
 

4.1.2 Definitions ............................... 
 

4.1.3 Literature Sources on Bioavailability .............. 
 

4.1.4 Lead Absorption-Bioavailability Relationships ....... 
 

4.1.5 Cellular and Subcellular Mechanisms of Lead
 

Absorption .............................. 
 

4.1.6 Factors Affecting Lead Absorption ............... 
 

2-38 

2-38 

2-40 

2-42 

2-44 

2-45 

2-45 

2-45 

2-46 

2-46 

2-46 

3-1 

3-1 

3-1 

3-2 

3-9 

3-9 

3-9 

3-10 

3-11 

3-11 

3-11 

3-11 

3-12 

3-12 

3-13 

3-13 

3-13 

4-1 

4-1 

4-1 

4-1 

4-2 

4-3 

4-3 

4-5 

viii 
TABLE OF CONTENTS (cont'd) 

Page 

4.1.7 Bioavailability of Lead in Soils and Dusts .......... 
 

4.1.7.1 

4.1.7.2 

4.1.7.3 

4.1.7.4
 

4.1.7.5
 

4.1.7.6
 

4.1.7.7 

Biophysico-Chemical and Environmental 
 

Features of the Exposure Matrix ........... 
 

Is There a Better Way To Classify 
 

Lead-Contaminated Sites? ............... 
 

Methodological Approaches To Quantifying
 

Bioavailability ...................... 
 

Determination of Absolute Bioavailability .... 
 

Absolute Versus Relative Bioavailability ..... 
 

Quantitative Experimental Models
 

of Human Lead Bioavailability ............ 
 

Summary and Advisory Overview for Lead
 

in Soils and Dust ..................... 
 

4.1.8 Bioavailability of Lead in the Diet ............... 
 

4.1.9 Bioavailability of Lead in Water ................. 
 

4.1.10 Bioavailability of Lead in Air .................. 
 

4.2	 USING THE INTEGRATED EXPOSURE UPTAKE 
 

BIOKINETIC MODEL FOR RISK ESTIMATION .......... 
 

4.2.1 Why Is Variability Important? .................. 
 

4.2.1.1 Intent of the Model and the Measure ........ 
 

4.2.1.2 Individual Geometric Standard Deviation ..... 
 

4.2.2 Variability Between Individuals Is Characterized by 
 

the Geometric Standard Deviation ............... 
 

4.2.3 Statistical Methods for Estimating the Geometric 
 

Standard Deviation from Blood Lead Studies ........ 
 

4.2.4 Choosing the Geometric Standard Deviation: 
 

Intra-Neighborhood Variability ................. 
 

4.2.5 Basis for Neighborhood Scale Risk Estimation ....... 
 

4.2.6 Relationship Between Geometric Standard Deviation 
 

and Risk Estimation ......................... 
 

4.2.7	 Risk Estimation at a Neighborhood or Community
 

Scale .................................. 
 

4.2.7.1 What Do We Mean by "Neighborhood" or 
 

Community" Risk? ................... 
 

4.2.7.2 Neighborhood Risk Estimation as the Sum
 

of Individual Risks ................... 
 

4.2.7.3 An Example for the "Sum of Individual 
 

Risks" Approach ..................... 
 

4.2.7.4 Assessment of Risk Using Grouped Data for
 

a Neighborhood ..................... 
 

4.2.7.5 Assessment of Risk with Neighborhood or
 

Neighborhood-Scale Input ............... 
 

4.3 ENVIRONMENTAL PATHWAY ANALYSIS ............. 
 

4-7 

4-7 

4-9 

4-10 

4-10 

4-12 

4-13 

4-16 

4-16 

4-19 

4-20 

4-21 

4-21 

4-21 

4-21 

4-23 

4-25 

4-26 

4-27 

4-28 

4-30 

4-30 

4-31 

4-32 

4-34 

4-36 

4-37 

ix 
TABLE OF CONTENTS (cont'd) 

Page 

4.3.1 Concept of Pathway Analysis .................. 4-37
 

4.3.2 Pathway Analyses by Linear Regression ........... 4-38
 

4.3.3 Pathway Analysis Using Structural Equation Models ... 4-39
 

4.3.4 Regression Analyses for Multiple Exposure Pathways: 
 

Soil Example ............................. 4-41
 

4.4	 USE OF DATA FROM BLOOD LEAD STUDIES .......... 4-42
 

4.4.1 Overview ............................... 4-42
 

4.4.2 Data Quality ............................. 4-45
 

4.4.3 Age of the Population Tested ................... 4-46
 

4.4.4 Time of the Year When Testing Was Done .......... 4-46
 

4.4.5 Concurrent Characterization of Lead Sources ........ 4-47
 

4.4.6 Demographics and Behavioral Factors That Affect 
 

Lead Exposure ............................ 4-48
 

4.4.7 Effect of Public Awareness or Educational
 

Intervention .............................. 4-48
 

4.4.8.	 Comparison of Observed and Predicted Blood 
 

Lead Concentrations ........................ 4-49
 

4.4.8.1 Were Important Sources of Lead Exposure
 

Overlooked? ........................ 4-49
 

4.4.8.2 Are There Interrupted or Enhanced Exposure 
 

Pathways at the Site? .................. 4-50
 

4.4.8.3 Are the Assumptions About Site-Specific Intake 
 

Rates and Uptake Parameters Valid? ........ 4-50
 

4.5	 ASSESSING THE RELATIONSHIP BETWEEN SOIL/DUST 
 

LEAD AND BLOOD LEAD ......................... 4-51
 

4.5.1 Assessing Reductions in Blood Lead .............. 4-51
 

4.5.2 Situations in Which the Use of the Integrated 
 

Exposure Uptake Biokinetic Model Is Uncertain ...... 4-53
 

4.5.2.1 Assessment of Risk with Community or 
 

Neighborhood-Scale Input ............... 4-53
 

4.5.2.2 Use of Surrogate Input Data from Models
 

or Surveys ......................... 4-53
 

4.5.2.3 Use of the Model To Assess Risk of Elevated 
 

Blood Lead at the Regional or State Level .... 4-53
 

4.5.2.4	 Use of the Model To Assess Trigger Levels 
 

for Soil Abatement at the Community,
 

Regional, or State Level ................ 4-54
 

4.5.3	 Factors That Constrain or Limit the Use of the 
 

Model .................................. 4-54
 

4.5.3.1 Data and Data Sets Used as Input for
 

the Integrated Exposure Uptake
 

Biokinetic Model ..................... 4-54
 

x 
TABLE OF CONTENTS (cont'd) 

Page 

4.5.3.2	 Biological and Exposure Parameters Used in
 

the Integrated Exposure Uptake Biokinetic
 

Model Bioavailability of Soil Lead ......... 4-56
 

4.6	 WHAT YOU NEED TO KNOW ABOUT BIOKINETICS ...... 4-58
 

4.6.1 Description of the Biokinetic Model .............. 4-58
 

4.6.2 Consequences of Biokinetic Parameters for
 

Site-Specific Risk Assessment .................. 4-60
 

4.7 ISSUES IN USE OF THE MODEL FOR PAINT CHIPS ...... 4-61
 

4.7.1 Inappropriateness of Use of the Integrated Exposure
 

Uptake Biokinetic Model for Paint Chip Ingestion ..... 4-61
 

4.7.2 Daily Intake of Paint Chips .................... 4-63
 

4.7.3 Relationship of X-Ray Fluorescence Lead Paint
 

Surface Loading to Lead Paint Concentration ........ 4-64
 

4.7.4 Dissolution of Paint Chips in Acid Environments ...... 4-64
 

4.7.5 Absorption of Lead Paint In Vivo ................ 4-65
 

5.	 APPLICATIONS WITH EXAMPLES ....................... 5-1
 

5.1 APPLICATIONS FOR POPULATION ESTIMATES ......... 5-1
 

5.2 APPLICATIONS WHERE ENVIRONMENTAL LEAD
 

CONCENTRATIONS CHANGE OVER TIME ............. 5-1
 

5.3 APPLICATIONS FOR PROBABILITY AND
 

RISK ESTIMATION .............................. 5-18
 

5.4 BATCH MODE INPUT AND STATISTICAL 
 

ANALYSES OF OUTPUT .......................... 5-21
 

5.5 SOIL LEAD ABATEMENT EXAMPLES ................ 5-28
 

6. REFERENCES ....................................... 6-1
 

APPENDIX A:	 How to Calculate the Geometric Standard Deviation from
 

Blood Lead Data, If You Must .................... A-1
 

APPENDIX B:	 Summary of Revisions to Lead Uptake Biokinetic Model 
 

Software Versions ............................ B-1
 

xi 
LIST OF TABLES
 

Number Page 

2-1	 Dietary Lead Intake for U.S. Children by Age, for Each Year
 

from 1978 to Present ............................... 2-31
 

2-2	 Estimates of Lead Intake from Consumption of Local Produce
 

by Children, Ages 2 to 6 Years, in Kellogg, Idaho ............ 2-33
 

2-3	 Estimates of Lead Intake from Consumption of Local Fish by
 

Children, Ages 2 to 6 Years, in Kellogg, Idaho .............. 2-34
 

2-4 Average Daily Water Intake in U.S. Children ............... 2-37
 

2-5 Tap Water Intake by Age Category ...................... 2-37
 

2-6	 Daily Intake of Soil and Dust Estimated from Elemental
 

Abundances ..................................... 2-39
 

2-7 Age-Specific Soil and Dust Intake ...................... 2-40
 

2-8	 Minimum Percentage Soil Intake as a Function of Age in Dutch
 

Children in Daycare Centers .......................... 2-44
 

3-1 Default Values for Model Parameters .................... 3-3
 

3-2 Format for Batch Mode Input Data File ................... 3-7
 

4-1	 Piecewise Linear Regression Models for Blood Lead Versus
 

Water Lead in Three Studies .......................... 4-20
 

4-2 Example of Neighborhood Risk Estimation with Grouped Data ... 4-35
 

4-3	 Example of Neighborhood Risk Estimation with Coarsely
 

Grouped Data .................................... 4-35
 

4-4	 Percentage Increase in Blood Lead Levels in Infant Male
 

Wistar Rats with 48-Hour Oral Exposure to Lead Acetate,
 

and to Lead Octoate and Lead Chromate Paints of Different
 

Particle Sizes .................................... 4-66
 

4-5	 Percentage Increase in Blood Lead Levels in Infant Male
 

Baboons with Chronic Exposure to Lead Paint, Lead Acetate,
 

and Other Lead Compounds .......................... 4-66
 

xii 
LIST OF TABLES (cont'd) 

Number Page 

4-6 Percentage Increase in Blood Lead Levels in Juvenile 

Baboons with Chronic Exposure to Lead Paint, Lead Acetate,
 

and Other Lead Compounds .......................... 4-67
 

5-1	 User-Selected Entries for Integrated Exposure Uptake
 

Biokinetic Model Worksheet for Example 5-2, Child
 

Born in 1975 .................................... 5-3
 

5-2	 User-Selected Entries for Integrated Exposure Uptake
 

Biokinetic Model Worksheet for Example 5-2, Child
 

Born in 1975 .................................... 5-3
 

5-3a	 Soil Lead Data Entry Worksheet for Child Exposed to
 

2000 Fg/g Since Age 0 (Birth) ......................... 5-6
 

5-3b	 Soil Lead Data Entry Worksheet for Child Exposed to
 

2000 Fg/g Since Age 1 .............................. 5-6
 

5-3c	 Soil Lead Data Entry Worksheet for Child Exposed to
 

2000 Fg/g Since Age 2 .............................. 5-7
 

5-3d	 Worksheet for Yearly Soil Lead Concentration for Hypothetical 
 

Children Moving from a Residence Where Soil Concentration is 
 

100 Fg/g to a Residence Where Soil Concentration is 
 

2000 μg/g ...................................... 5-7
 

5-4	 Predicted Annual Average Blood Lead Concentrations for 
 

Hypothetical Children Moving from a Residence Where Soil 
 

Concentration is 100 Fg/g to a Residence Where Soil 
 

Concentration is 2000 μg/g .......................... 5-8
 

5-5a	 Soil Lead Data Entry Worksheet for Child with Soil Abated to
 

100 Fg/g Since Age 0 (Birth) .......................... 5-9
 

5-5b	 Soil Lead Data Entry Worksheet for Child with Soil Abated to
 

100 Fg/g Since Age 1 .............................. 5-10
 

5-5c	 Soil Lead Data Entry Worksheet for Child with Soil Abated to
 

100 Fg/g Since Age 2 .............................. 5-10
 

5-5d	 Worksheet for Hypothetical Children in a Neighborhood
 

Where Soil Concentration is Reduced from 2000 Fg/g
 

to 100 μg/g ..................................... 5-11
 

xiii 
LIST OF TABLES (cont'd) 

Number Page 

5-6 Predicted Blood Lead Concentrations for Hypothetical 

Children in a Neighborhood Where Soil Concentration
 

Is Reduced from 2000 μg/g to 100 μg/g ................... 5-11
 

5-7	 Neighborhood Identifiers and Distance from Stack
 

for Kellogg, Idaho, Study ............................ 5-14
 

5-8	 Observed and Estimated Air, Soil, and Dust Lead
 

Concentrations for Use in Historical Exposure
 

Reconstructions in Silver Valley Communities .............. 5-15
 

5-9	 User-Selected Entries for Integrated Exposure Uptake
 

Biokinetic Model Worksheet for Example 5-5, Child
 

Born in Kellogg, Idaho, in 1983 ........................ 5-16
 

5-10	 User-Selected Entries for Integrated Exposure Uptake
 

Biokinetic Model Worksheet for Example 5-5, Child
 

Born in Smelterville, in Kellogg, Idaho, in 1983 ............. 5-17
 

5-11	 User-Selected Entries for Integrated Exposure Uptake
 

Biokinetic Model Worksheet for Example 5-5 ............... 5-17
 

5-12	 Effects of Geometric Standard Deviation on the
 

Probability of Exceeding 10 Fg/dL, Using Only 
 

Default Exposure Parameters, for Children
 

Ages 24 to 35 months .............................. 5-19
 

5-13 Range Finding Run for Target Soil Lead Concentration ........ 5-30
 

5-14 Focused Run for Target Soil Lead Concentration ............. 5-30
 

5-15 Verification Run for Target Soil Lead Concentration .......... 5-31
 

A-1	 Cells of Blood Lead Levels in 165 Midvale 
 

Children, by Paint Removal Status, Age, and 
 

Intervals of 250 Fg/g in Soil and Dust Lead ................ A-3
 

A-2	 Geometric Mean and Geometric Standard Deviation
 

of Blood Leads in Cells or Groups, by Paint 
 

Removal Status, Age, and Intervals of 250 F/g
 

in Soil and Dust Lead .............................. A-8
 

A-3 Stem and Leaf Plot of Geometric Standard Deviation 

for Midvale Children ............................... A-13
 

xiv 
LIST OF TABLES (cont'd) 

Number Page 

A-4	 Stem and Leaf Plot of Geometric Standard Deviation
 

for Midvale Children (Weighted by Degrees of Freedom) ....... A-14
 

B-1	 Summary of Revisions to Lead Uptake Biokinetic Model
 

Software from Lead 0.2 to Lead 0.4 ..................... B-2
 

B-2	 Summary of Revisions to Lead Uptake Biokinetic Model
 

Software from Lead 0.4 to Lead 0.5 ..................... B-3
 

B-3	 Summary of Revisions to Lead Uptake Biokinetic Model
 

Software from Lead 0.5 to Lead 0.99d ................... B-4
 

xv 
LIST OF FIGURES
 

Number Page 

1-1	 Conceptual diagram of the movement of environmental lead into 
 

and through the human body .......................... 1-4
 

1-2	 Components of the Integrated Exposure Uptake Biokinetic Model, 
 

showing environmental exposure sources and pathways, 
 

absorption compartments, critical body tissue compartments, and 
 

elimination pathways ............................... 1-8
 

1-3	 Categories of application of the Integrated Exposure Uptake 
 

Biokinetic Model ................................. 1-26
 

2-1 Schematic diagram of the overall functions of the lead model ..... 2-1
 

2-2 Decision diagram for the air lead menu options .............. 2-6
 

2-3 Decision diagram for the dietary lead menu options ........... 2-8
 

2-4 Decision diagram for the drinking water lead menu options ...... 2-10
 

2-5 Decision diagram for the soil/dust lead menu options .......... 2-12
 

2-6	 Decision diagram for the alternate lead source menu
 

options ........................................ 2-16
 

2-7	 Decision diagram for the absorption/bioavailability menu
 

options ........................................ 2-18
 

2-8 Decision diagram for the multiple simulation menu options ...... 2-22
 

2-9 Decision diagram for the batch mode menu options ........... 2-25
 

2-10	 Historical relationship between lead in gasoline and lead in air
 

in the United States ................................ 2-28
 

2-11 Integrated Exposure Uptake Biokinetic Model sample worksheet .. 2-47
 

3-1 Lead model menu tree .............................. 3-2
 

4-1	 Schematic drawing of the enterocyte showing possible mechanisms
 

for lead absorption ................................ 4-4
 

4-2	 Dose-dependent relationship between dietary lead (formula
 

mixed with water) and blood lead in infants ................ 4-6
 

xvi 
LIST OF FIGURES (cont'd) 

Number Page 

4-3 The time-course of bioavailability of lead in the blood and
 

in the brain of juvenile rats following a single dose ........... 4-11
 

4-4 Kinetics of absorption during repeated dosing ............... 4-11
 

4-5	 Under conditions of equilibrium, the amount of lead as the 
 

free ion is limited by mass balance dissolution of the solid
 

phase ......................................... 4-15
 

4-6	 Under physiological conditions, free lead ion is removed from 
 

solution by active and passive absorption mechanisms 
 

potentially shifting the equilibrium of the dissolution
 

process far to the left ............................... 4-15
 

4-7	 The impact of the relative positions of the level of concern 
 

and the geometric mean on the proportion of children 
 

"at risk" for two populations with different geometric 
 

standard deviations ................................ 4-24
 

4-8 Probability density of blood lead in houses 1 to 4 ............ 4-33
 

4-9 Exposure pathways of lead in the environment .............. 4-37
 

4-10	 Biokinetic compartments, compartmental lead flows, and 
 

uptake pathways in the Integrated Exposure Uptake 
 

Biokinetic Model ................................. 4-60
 

xvii 
LIST OF SCREENS
 

Number Page 

2-1 The main menu ................................... 2-3
 

2-2 The general help menu .............................. 2-4
 

2-3 The information menu .............................. 2-5
 

2-4 The air lead menu ................................. 2-5
 

2-5 The dietary lead main menu .......................... 2-7
 

2-6 The alternative dietary source menu ..................... 2-9
 

2-7 The drinking water lead main menu ..................... 2-9
 

2-8 The age-specific drinking water consumption menu ........... 2-11
 

2-9 The soil and dust main menu .......................... 2-11
 

2-10 The multiple dust source menu ........................ 2-13
 

2-11 The alternative indoor dust menu ....................... 2-14
 

2-12 The soil/dust ingestion rate menu ....................... 2-15
 

2-13 The alternate source lead menu ........................ 2-15
 

2-14 The absorption/bioavailability menu ..................... 2-19
 

2-15 The maternal/fetal lead exposure menu ................... 2-19
 

2-16 Single simulation using the program processing menu .......... 2-20
 

2-17 Multiple simulation using the program processing menu ........ 2-21
 

2-18 Selection of media for multiple range run .................. 2-23
 

2-19 Range selection during multiple processing ................ 2-23
 

2-20	 Using multiple simulation to find acceptable media concentrations
 

for a predetermined blood lead concentration ............... 2-24
 

2-21 Running the model in batch mode ....................... 2-24
 

xviii 
LIST OF SCREENS (cont'd) 

Number Page 

2-22 Data entry for air ................................. 2-30
 

2-23 Using dietary lead intake for a child born in 1983 ............ 2-34
 

2-24	 Using dietary lead intake from local vegetables and 
 

fish in Kellogg ................................... 2-35
 

5-1	 Multiple runs probability density function for soil 
 

lead = 1,000 μg/g, dust lead = 0 to 1,500 μg/g, by 
 

steps of 250 μg/g (Runs 1 through 7) in Example 5-6 .......... 5-20
 

5-2	 Multiple runs probability of exceedance of blood lead
 

levels for soil lead = 1,000 μg/g, dust lead = 0 to 
 

1,500 μg/g, by steps of 250 μg/g (Runs 1 through 7) 
 

in Example 5-6 ................................... 5-21
 

5-3	 Relationship of predicted blood lead to dust lead 
 

in Example 5-6 ................................... 5-22
 

xix 
TECHNICAL REVIEW WORKGROUP FOR LEAD
 

Harlal Choudhury
 

U.S. Environmental Protection Agency
 

Environmental Criteria and Assessment
 

Office
 

26 West Martin Luther King Dr.
 

Cincinnati, OH 45268
 

Barbara Davis
 

U.S. Environmental Protection Agency
 

(5204G)
 

401 M St. SW
 

Washington, DC 20460
 

Rob Elias
 

U.S. Environmental Protection Agency
 

(MD-52)
 

Environmental Criteria Assessment Office
 

Research Triangle Park, NC 27711
 

Susan Griffin (Chair)
 

U.S. Environmental Protection Agency
 

Region 8 (8 HWM-SM)
 

999 18th St., Suite 500
 

Denver, CO 80202
 

Karen Hogan
 

U.S. Environmental Protection Agency
 

(7404)
 

401 M St. SW
 

Washington, DC 20460
 

Mark Maddaloni 

U.S. Environmental Protection Agency 

Region 2 

Emergency and Remedial Response 

Division 

26 Federal Plaza 

New York, NY 10278 

Allan Marcus 

U.S. Environmental Protection Agency 

(MD-52) 

Environmental Criteria and Assessment 

Office 

Research Triangle Park, NC 27711 

Roy Smith
 

U.S. Environmental Protection Agency
 

Region 3 (3 HW15)
 

Hazardous Waste Management Division
 

841 Chestnut St.
 

Philadelphia, PA 19107
 

Pat Van Leeuwen
 

U.S. Environmental Protection Agency
 

Region 5 (HSRLT-5J)
 

Waste Management Division
 

77 West Jackson Blvd.
 

Chicago, IL 60604
 

Chris Weis
 

U.S. Environmental Protection Agency
 

Region 8 (8 HWM-SM)
 

999 18th St., Suite 500
 

Denver, CO 80202
 

Paul White 

U.S. Environmental Protection Agency 

(8603) 

Office of Health and Environmental 

Assessment 

401 M St., SW 

Washington, DC 20460 

xx 

GLOSSARY OF MODEL TERMS 

Absorbed dose - The amount of a substance penetrating an absorption barrier (the exchange 

boundaries) of an organism, via either physical or biological processes. 

Absorption barrier - Any of the exchange barriers of the body that allow differential transport 

of various substances across a boundary. Examples of absorption barriers are the skin, lung 

tissue, and gastrointestinal tract wall. 

Accuracy - The measure of the correctness of data, as given by the difference between the 

measured value and the true or standard value. 

Ambient - Surrounding conditions. 

Ambient measurement - The measurement (usually of the concentration of a chemical or 

pollutant) taken in an ambient medium, normally with the intent of relating the measured 

value to the exposure of an organism that contacts that medium. 

Ambient medium - One of the basic categories of material surrounding or contacting an 

organism (e.g., outdoor air, indoor air, water, or soil) through which chemicals or pollutants 

can move and reach the organism. (See biological medium, environmental medium.) 

Arithmetic mean - The sum of all the measurements in a data set divided by the number of 

measurements in the data set. 

Background level (environmental) - The concentration of substance in a defined control area 

during a fixed period of time before, during or after a data gathering operation. 

Bias - A systematic error inherent in a method or caused by some feature of the measurement 

system. 

Bioavailability - The fraction of intake at a portal of entry into the body (lung, gut, skin) that 

enters the blood. Bioavailability is typically a function of chemical properties, physical state 

of the material that an organism ingests or inhales, and the ability of the individual organism 

to physiologically absorb the chemical. The absorption rate varies widely by type of 

substance and can greatly influence the toxicity of lead over that acute timeframe. 

Biokinetics - processes affecting the movement of molecules from one internal body 

compartment to another, including elimination from the body. 

Biological measurement - A measurement taken in a biological medium. For the purpose of 

exposure assessment via reconstruction of dose, the measurement is usually of the 

concentration of a chemical/metabolite or the status of a biomarker, normally with the intent 

of relating the measured value to the internal dose of a chemical at some time in the past. 

xxii 
(Biological measurements are also taken for purposes of monitoring health status and 

predicting effects of exposure). (See ambient measurement.) 

Biological medium - One of the major categories of material within an organism (e.g., blood, 

adipose tissue, or breath) through which chemicals can move, be stored, or be biologically, 

physically, or chemically transformed. (See ambient medium, environmental medium.) 

Body burden - The amount of a particular chemical stored in the body at a particular time, 

especially a potentially toxic chemical in the body as a result of exposure. Body burdens can 

be the result of long term or short term storage, for example, the amount of a metal in bone, 

the amount of a lipophilic substance such as PCB in adipose tissue, or the amount of carbon 

monoxide (as carboxyhemoglobin) in the blood. 

Comparability - The ability to describe likenesses and differences in the quality and relevance 

of two or more data sets. 

Compartment - A distinct anatomical organ, tissue, fluid pool, or group of tissues within the 

body that are regarded as "kinetically homogeneous." 

Dose - The amount of a substance available for interaction with metabolic processes or 

biologically significant receptors after crossing the outer boundary of an organism. The 

potential dose is the amount ingested, inhaled, or applied to the skin. The applied dose is the 

amount of a substance presented to an absorption barrier and available for absorption 

(although not necessarily having yet crossed the outer boundary of the organism). The 

absorbed dose is the amount crossing a specific absorption barrier (e.g., the exchange 

boundaries of skin, lung, and digestive tract) through uptake processes; internal dose is a 

more general term denoting the amount absorbed, without respect to specific absorption 

barriers or exchange boundaries. The amount of the chemical available for interaction by any 

particular organ or cell is termed the delivered dose for that organ or cell. 

Environmental medium - One of the major categories of material found in the physical 

environment that surrounds or contacts organisms (e.g., surface water, ground water, soil, or 

air) and through which chemicals or pollutants can move and reach the organisms. (See 

ambient medium, biological medium.) 

Exposure - Contact of a chemical, physical, or biological agent with the outer boundary of an 

organism. Exposure is quantified as the concentration of the agent in the medium in contact 

integrated over the time duration of that contact. 

Exposure pathway - The physical course a chemical or pollutant takes from the source to the 

organism exposed. 

Exposure route - The way a chemical or pollutant enters an organism after contact (e.g., by 

ingestion, inhalation, or dermal absorption). 

xxiii 
Exposure scenario - A set of facts, assumptions, and inferences about how exposure takes 

place that aids the exposure assessor in evaluating, estimating, or quantifying exposures. 

Geometric mean - The nth root of the product of n values. Also, the exponential function of 

the mean or expected value of the natural logarithm of a variable. 

Geometric standard deviation (GSD) - The exponential function of the standard deviation of 

the natural logarithm of a variable. 

Guidelines - Principles and procedures to set basic requirements for general limits of 

acceptability for assessments. 

Intake - The process by which a substance crosses the outer boundary of an organism without 

passing an absorption barrier (e.g., through ingestion or inhalation). (See also "potential 

dose"). 

Internal dose - The amount of a substance penetrating across the absorption barriers (the 

exchange boundaries) or an organism, via either physical or biological processes. 

Matrix - A specific type of medium (e.g., surface water, drinking water) in which the analyte 

of interest may be contained. 

Median value - The value in a measurement data set such that half the measured values are 

greater and half are less. 

Monte Carlo technique - A repeated random sampling from the distribution of values for each 

of the parameters in a generic (exposure or dose) equation to derive an estimate of the 

distribution of (exposures or doses in) the population. 

Pathway - The physical course a chemical or pollutant takes from the source to the organism 

exposed. 

Pharmacokinetics - The study of the time course of absorption, distribution, metabolism, and 

excretion of a foreign substance (e.g., a drug or pollutant) in an organism's body. 

Potential dose - The amount of a chemical contained in material ingested, air breathed, or 

bulk material applied to the skin. 

Precision - A measure of the reproducibility of a measured value under a given set of 

conditions. 

Probability samples - Samples selected from a statistical population such that each sample has 

a known probability of being selected. 

xxiv 
Random samples - Samples selected from a statistical population such that each sample has an 

equal probability of being selected. 

Range - The difference between the largest and smallest values in a measurement data set. 

Reasonable worst case exposure or risk range - The lower portion of the "high end" of the 

exposure, dose or risk distribution. The reasonable worst case conceptually should be 

targeted at above the 90th percentile in the distribution, but below about the 98th percentile 

("maximum exposure or risk range"). 

Representativeness - The degree to which a sample is, or samples are, characteristic of the 

whole medium, exposure, or dose for which the samples are being used to make inferences. 

Risk - The probability of deleterious health or environmental effects. 

Route - The way a chemical or pollutant enters an organism after contact (e.g., by ingestion, 

inhalation, or dermal absorption). 

Sample - A small part of something designed to show the nature or quality of the whole. 

Exposure-related measurements are usually samples of environmental or ambient media, 

exposures of a small subset of a population for a short time, or biological samples, all for the 

purpose of inferring the nature and quality of parameters important to evaluating exposure. 

Scenario evaluation - An approach to quantifying exposure by measurement or estimation of 

both the amount of a substance contracted, and the frequency/duration of contact, and 

subsequently linking these together to estimate exposure or dose. 

Structural Equations Model - A statistical model of a process in which several regression 

equations are solved simultaneously, and outputs or responses from one equation may be used 

as inputs or predictors in another equation. Useful in pathway modeling. 

Surrogate data - Substitute data or measurements on one substance used to estimate 

analogous or corresponding values of another substance. 

Uptake - The process by which a substance crosses an absorption barrier and is absorbed into 

the body. 

xxv