EPA PB93-963510 OSWER #9285.7-15-1 February 1994



# GUIDANC E MANUAL FO R THE IEUBK MO DEL FOR L EAD IN CHI LDREN

Office of Solid W aste and E merg ency R esponse U.S. Environm ental Protection Agency Washingt on, DC 20 460NOTICE This document provides guidance to EPA staff. I t 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 reg ulations, nor is it a regulation itself. Thus, it cannot impose legally -binding requirements on EPA, States, or the regula ted 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. E NVIRONMENTAL 

### P ROTECTION 

### A GENCY 

### T ECHNICAL 

### R EVIEW 

### W ORKGROUP FOR 

### L EAD The Technical Review Workgroup for L ead (TRW) is an interoffice workgroup c onvened by the U.S. EPA Office of Solid Waste and Emergency Response/Office of Emergenc y and Remedial Response (OSWER/OERR).

Region 8 Susan G riffin Denver, CO

Region 2 Mark Maddaloni New York, NY Region 3 Roy S mith Philadelphia, PA Region 5 Patricia VanLeeuwen Chic ago, IL Region 8 Chris We is Denver, CO NCEA/Washington Karen Hogan C HAIRP ERSON

M EMBERS NCEA/Washington Paul Wh ite NCEA /Cincin nati Harlal C houdhu ry NCEA/Research Triangle Park Robert Elias NCEA/Research Triangle Park Allan Marcus ORD/Washington Barbara Davi s

### 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 27711PREFACE 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
i ilevels 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
i iiMarch, 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.
i vWhile 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.

vTABLE OF CONTENTS Page PREFACE

............................................. ii LIST OF TABLES

....................................... xii LIST OF FIGURES
....................................... xvi LIST OF SCREENS
...................................... x v

i i i 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 viTABLE 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

viiTABLE 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
vi iiTABLE 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

i xTABLE 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

xTABLE 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

xiLIST 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

xiiLIST 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 F g/g Since Age 0 (Birth)

......................... 5-6 5-3b Soil Lead Data Entry Worksheet for Child Exposed to 2000 F g/g Since Age 1

.............................. 5-6 5-3c Soil Lead Data Entry Worksheet for Child Exposed to 2000 F g/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 F g/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 F g/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 F g/g Since Age 0 (Birth)

.......................... 5-9 5-5b Soil Lead Data Entry Worksheet for Child with Soil Abated to 100 F g/g Since Age 1

.............................. 5-10 5-5c Soil Lead Data Entry Worksheet for Child with Soil Abated to 100 F g/g Since Age 2

.............................. 5-10 5-5d Worksheet for Hypothetical Children in a Neighborhood Where Soil Concentration is Reduced from 2000 F g/g to 100 μg/g

..................................... 5-11

xi iiLIST 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 F g/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 F g/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

x

i vLIST 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

xvLIST 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

xviLIST 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

xviiLIST 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

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vi iiLIST 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

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i xTECHNICAL 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

xxGLOSSARY 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.
xxi i(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).

xxi iiExposure 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.

xx i vRandom 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.

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