1. BEFORE YOU START 

1.1 BACKGROUND: PURPOSE AND DEVELOPMENT OF THE 

MODEL 

The Integrated Exposure Uptake Biokinetic (IEUBK) Model for Lead in Children is a 

stand alone, PC compatible software package. It allows the user to estimate, for a 

hypothetical child or population of children, a plausible distribution of blood lead 

concentrations centered on the geometric mean blood lead concentration predicted by the 

model from available information about children's exposure to lead. From this distribution, 

the model calculates the probability that children's blood lead concentrations will exceed the 

user selected level of concern (default 10 Fg/dL). The user can then explore an array of 

possible changes in exposure media that would reduce the probability that blood lead 

concentrations would be above this level of concern. 

The model should be viewed as a tool for making rapid calculations and recalculations 

of an extremely complex set of equations that includes scores of exposure, uptake, and 

biokinetic parameters. This Guidance Manual concisely describes key features of the 

conceptual underpinnings of the IEUBK model, its evolution and development, its 

capabilities, and its limitations. The Manual then goes on to offer guidance on the use of the 

model as a risk assessment tool while cautioning against a number of possible misapplications 

of the model. A detailed description of the equations and parameters used in the model is 

provided in the Technical Support Document: Parameters and Equations Used in the 

Integrated Exposure Uptake Biokinetic Model for Lead in Children (a companion document 

to this Guidance Manual). 

1.1.1 Description of the Model 

The IEUBK Model is a simulation model. As a risk assessment tool, it can be a useful 

component of remediation strategies for lead in the human environment. The simulation of 

childhood lead exposure and retention is only one part of the risk assessment process. It is 

important to note that the model alone does not determine the level of cleanup required for a 

specific site. Rather, it predicts the likely blood lead distribution for children given the 

exposure to lead at that site, and the probability that children exposed to lead in that 

environment will have blood lead concentrations exceeding a health-based level of concern. 

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Blood lead concentrations are not only indicators of recent exposure, but also are the 

most widely used index of internal lead body burdens associated with potential health effects. 

Health effects of concern have been determined to be associated with childhood blood lead 

concentrations at or below 10 Fg/dL (U.S. Environmental Protection Agency, 1986, 1990; 

CDC, 1991). The probability that children will have blood lead levels exceeding this level of 

concern is an important consideration for a risk assessor in compiling and evaluating all 

information applicable to a site to enable remediation decisions. 

The IEUBK model can be applied at several different scales of application, but the 

interpretation of the model output and the form of the model or subsequent risk estimates is 

different for each application. In most uses of the model, a site is a spatial domain that is 

appropriate for remediation decisions, typically a residential yard with a single housing unit, 

or an equivalent area for multi-unit buildings or for undeveloped lots. The home and its 

surrounding yard is the basic unit for risk analysis because lead exposure for pre-school 

children commonly occurs within this domain. In Sections 1.4.4.2 and 4.2 we will describe 

an array of applications of the IEUBK model based on aggregating clusters of sites. The 

array is: 

A: One location 

A1: one living unit, one child; 

A2: one living unit, more than one child; 

A3: more than one living unit, more than one child, homogeneous media 

concentrations; 

B: Multiple locations, one neighborhood, homogeneous media concentrations 

C: Multiple locations, one neighborhood, heterogeneous media 

concentrations; 

D: Multiple locations, more than one neighborhood, heterogeneous media 

concentrations; 

In category A, risk is calculated as the probability that, in a single child at a single site 

with the specified exposure scenario, the child's blood lead concentration will exceed the 

level of concern. The probability distribution describes the likely variability in blood lead for 

a child with a given exposure scenario. The best single-number prediction of blood lead 

concentration is the geometric mean of the distribution of blood lead concentrations that may 

occur for a child with the specified exposure scenario. This single-child assessment is used to 

evaluate remediation options on a house-by-house or yard-by-yard basis. 

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In categories B, C, and D, a frequency distribution of the individual risk of exceeding a 

blood lead level of concern is obtained. The percentage of children in multiple sites that are 

likely to have a blood lead concentration exceeding the level of concern can then be 

calculated. For category B, where all children of the same age have the same exposure 

scenario, this can be done with a single run of the IEUBK model. For categories C and D, 

where distinct subgroups have different exposure scenarios, risk must be calculated by 

aggregating the results from a number of model runs. Risk estimation for more than one 

neighborhood, for category D, has the added complication that a variety of model parameters 

may differ between neighborhoods, and within each neighborhood. Therefore, environmental 

lead concentrations may differ between neighborhood subgroups. 

1.1.2 Simulation of Childhood Lead Exposure and Retention 

Lead is a naturally occurring nonnutrient metal that follows environmental pathways 

similar to those of nutrient metals such as calcium. In the human environment, these 

pathways or routes of exposure transfer lead from sources such as food, drinking water, air, 

soil, and dust, to the human body by means of ingestion or inhalation. There are important 

analogies to be made between lead and calcium that contribute to our understanding of the 

biological behavior of lead. These analogies have aided in the formulation of the lead model. 

In particular, the nature of gut absorption of lead and calcium may be similar. Childhood 

growth and development of bone and soft tissue which require calcium influence the uptake 

of environmental lead from the gut. In addition to similarities in absorption, both lead and 

calcium are stored in quantity and subsequently released from bone tissue. 

Shown conceptually on Figure 1-1, inhaled or ingested lead is absorbed through the 

lungs or gut into the blood stream where it is transferred to body tissues, including bone 

tissues. After a period of time, this lead returns to the blood stream where it is transferred to 

other tissues or eliminated with urine. Lead may also be eliminated from the body with 

sweat, hair or sloughed epidermal tissue, or it may be transferred through the liver and bile 

duct back to the gut where it passes out of the body with feces. 

In Figure 1-1, the oval shapes show environmental lead media, and some of the 

pathways between them. The large rectangle shows the compartment that is central to lead 

distribution in the child, the blood plasma pool and associated extra-cellular fluid. Each 

lower rectangle shows a compartment in the child's body where lead may be retained. The 

excretion of lead from the body is shown by the circles. 

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Figure 1-1. Conceptual diagram of the movement of environmental lead into and 

through the human body. The oval shapes show environmental media and 

the pathways of uptake. The large rectangle is the blood plasma 

compartment central to the distribution of lead in the body. 

The foundation of the present IEUBK model is the construction of a detailed and 

thorough exposure scenario for children aged 0 to 84 months that can be adjusted to match 

the exposure of any child. The user starts with exposure information specific to these 

children and accepts generalized assumptions about any additional information required to 

complete the exposure scenario. The site-specific information usually consists of 

environmental media concentrations such as soil lead concentrations. 

The model inserts default values whenever site-specific information is not used. The 

default values (e.g., dietary lead concentrations and consumption values) are typical of a 

child's environment in the sense that they are broad-based estimates of the expected 

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environment of a child. These default values are not necessarily appropriate for every site 

and should be reviewed by the user for every site-specific application. 

This model uses standard age-weighted exposure parameters for consumption of food, 

drinking water, soil, and dust, and inhalation of air, matched with site-specific concentrations 

of lead in these media, to estimate exposure for the child. The model simulations represent 

chronic exposure and do not incorporate the variability in consumption patterns and media 

concentrations on a daily or seasonal basis. The model includes continuous growth of the 

child and simulates the changing environment of the child on a yearly basis. In theory, the 

exposure component of the model would apply to a single child or to any number of children 

with the same lead exposure scenario. With the proper substitution for media concentrations, 

the exposure component (but not the biokinetic component) would also apply to any other 

substance with sources and pathways of exposure similar to lead. 

The model simulates lead uptake, distribution within the body, and elimination of lead 

from the body. The uptake portion of the model takes into consideration two mechanisms of 

absorption of lead in the digestive tract: saturable and non-saturable. Elimination of lead is 

modeled through several routes: urine, gastro-intestinal excretion, and sloughing of 

epidermal tissue, including hair and nails. 

1.1.3 Historical Evolution from Slope Factor Models to the IEUBK Model 

An explicit mathematical method for estimating the likely risk of elevated blood lead 

concentrations in young children has previously been used by the Environmental Protection 

Agency as one of its tools for developing the National Ambient Air Quality Standard for Lead 

and the National Primary Drinking Water Regulation for Lead. The method has historically 

been based mainly on an estimation of relationships between lead concentrations in children's 

blood and lead concentrations in specific individual environmental media such as air, water, 

soil and dust, based on empirical observations derived from experimentally controlled human 

exposure, animal toxicological studies, and epidemiological analyses. Such relationships also 

provide a basis for estimating the probability that elevated blood lead concentrations exceed a 

level of concern due to exposure to environmental lead in these media. 

A mathematical approach of this type was used to evaluate potential alternative air lead 

standards based on health effects criteria (U.S. Environmental Protection Agency, 1977, 

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1978, 1989a). The relationship between blood lead and lead in environmental media was 

estimated statistically, both for adults and children (U.S. Environmental Protection Agency, 

1986, 1989a). While the relationship was somewhat non-linear at blood lead concentrations 

above about 40 Fg/dL in adults and 30 Fg/dL in children, it was nearly linear at lower blood 

lead concentrations of interest. The relationship between blood lead and environmental lead 

concentrations in different media (air, water, soil, dust, food) was estimated using a model 

linear in lead concentrations. The linear regression coefficients between blood lead and lead 

in each of the environmental media have since become known as the slope factors for the 

media. 

As more evidence has become available, it has become clear that these slope factors can 

not be regarded as universal constants that are the same everywhere, for all children at all 

sites. Some of the problems involved in the use of slope factors have been discussed by the 

U.S. Environmental Protection Agency (1989a) and by Brunekreef et al. (1984). In the 

development of improved lead models (U.S. Environmental Protection Agency 1986, 1989a), 

the following points were discussed: 

(1) Slope factors are a function of many factors: media ingestion rates; 

bioavailability and absorption of lead from the medium; and biological 

kinetics of lead retention and elimination in the child. Biological and 

physical differences between sites and study populations cannot be 

incorporated explicitly and quantitatively into regression slope factors 

from different studies. 

(2) Slope factors for a single medium, such as lead in air or lead in soil, may 

provide only a very incomplete picture of total lead exposure from a 

particular source, even if the source is identified with the medium. A 

single medium such as household dust may contain lead from many 

sources, and lead from a single source such as exterior lead-based paint 

may contribute to several exposure media pathways to the child. 

Therefore, in 1985, the EPA Office of Air Quality Planning and Standards (OAQPS) 

initiated a project that would allow the calculation of blood lead concentrations in children 

exposed to differing arrays of concentrations of lead in air, soil, and dust. This model, called 

the Uptake/Biokinetic (or UBK) model for lead, was a computer simulation model based on 

the biokinetic model for lead in children developed by N. Harley and T. Kneip (1985). The 

biokinetic parameters for the UBK model were extrapolated from long-term feeding studies 

on infant and juvenile baboons (Mallon, 1983), autopsy data on human children, human 

infant feeding studies, and other sources. The exposure model that was coupled to the 

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biokinetic model was developed by OAQPS. Model calibration and validation was done 

using data from the 1983 EPA/CDC/Montana study on children in East Helena, Montana, 

who lived in the vicinity of a large primary lead smelter. The modeling approach was 

reviewed and approved by EPA's Clean Air Science Advisory Committee (CASAC) in 1990. 

The overall framework of both the UBK and IEUBK models is shown in Figure 1-2. 

The oval shapes show environmental lead concentrations and the funnel-shaped symbols show 

lead intake from the environment at the portals of entry, the lung and the gut. These are the 

exposure/intake components of the IEUBK model. The next large rectangle shows the gut 

not only as the main portal of entry for lead from most exposure media, but also as the site 

for key absorption/uptake components of the IEUBK model for the evaluation of lead from 

soil, dust, diet, and drinking water. The very large rectangle shows the child's blood lead, 

partitioned into plasma-extracellular fluid and red blood cells. The two boxes to the right of 

the blood lead pool sketch the bone and soft tissue pools, and the elimination pathways are 

shown as circles. The right-hand box shows the blood lead concentration in the child, and 

the subdivisions show the estimated contribution of each medium to the child's blood lead 

concentration. In the example in Figure 1-2, we have assumed that all external lead media 

have been used in the IEUBK model, as have all internal lead sources. There is no 

unattributable component called "background". The attribution of specific fractions of blood 

lead to uptake from specific media is not as subject to statistical artifacts, since pathways 

from soil lead and air lead to dust lead are also included in the IEUBK model. 

In all particulars, the present version of the model, the IEUBK model, may be 

considered an enhancement and extension of the UBK model. Theoretically, in situations 

where the child has constant long-term or chronic lead exposure, both the slope factor 

approach and the UBK model (now the IEUBK model) should produce similar results when 

sufficient data exist to correctly characterize lead exposure, absorption, and biokinetics. 

The IEUBK Model addresses three emerging paradigms of environmental risk 

assessment. 

(1) Assessments that recognize the multimedia nature of exposures to 

environmental toxicants are a significant improvement in assessing health 

risks. Assessments restricted to single pathways of exposure can overlook 

situations where integrated multimedia exposures are high enough to 

trigger health concerns. The lead model is structured to integrate 

exposures occurring through air, water, food, soil, and dust in estimating 

the blood lead levels in children in realistic environmental settings. 

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Air Pb 

Dust Pb 

Soil Pb 

Water Pb 

Diet Pb 

Other Pb 

Inhalation 

Ingestion 

Ingestion 

Ingestion 

Ingestion 

Ingestion 

Lung 

Gut 

Plasma+ 

ExtraCellular 

Fluid 

Red 

Blood 

Cells 

Cortical and 

Trabecular 

Bone 

Liver, 

Kidney, 

Other 

Soft 

Tissues 

Urine 

Hair 

Sweat 

Nails 

Feces 

From Bone 

From Air 

From Dust 

From Soil 

From Water 

From Diet 

From Other 

Environment Exposure/ Absorption/ Blood Tissues Elimination Blood 

Intake Uptake Lead 

Biokinetics 

Figure 1-2. Components of the IEUBK Model, showing environmental exposure sources 

and pathways, absorption compartments, critical body tissue compartments, 

and elimination pathways. 

(2) Pharmacokinetic information can strengthen the validity of environmental 

health assessments in comparison with more traditional methods that 

address only external dose or intake of a compound. Internal measures of 

dose that are pertinent to the biological effects exerted by a compound 

form an improved metric for risk assessment. The IEUBK estimates of 

blood lead concentrations as an internal indicator of potential health risk 

are based on pharmacokinetic modeling of lead absorption, transport, 

redistribution, and elimination. 

(3) Environmental assessments need to address the substantial variability in 

exposure and risk resulting from these factors. Single point estimates of 

exposure or risk are of limited utility. Individuals differ in their 

surroundings, behavior, and physiological status. The Lead Model 

addresses variability through the estimation of probability distributions of 

blood lead levels for children exposed to similar environmental 

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concentrations of lead. Through systematic application of the model, data 

on the variability of levels of environmental lead contamination can be 

translated into estimates of the distribution of blood lead levels within 

populations of children. 

1.1.4 Using the IEUBK Model for Risk Estimation 

The IEUBK Model for lead is designed to facilitate: (a) rapid delineation of the 

relationship between environmental lead and blood lead in children; and (b) calculation of the 

risk of elevated blood lead (i.e., the probability of a given child or a group of children having 

blood lead concentrations exceeding a specified level of concern). As such, the IEUBK 

Model provides a tool for site-specific risk assessment for young children exposed to lead 

from different media and through different pathways in their environment, with particular 

emphasis on lead in air, water, soil, and household dust. Many other applications are 

possible. The intended applications of the IEUBK model are to: 

(1) Provide a summary of children's long-term, primarily residential, 

exposure to lead; 

(2) Provide a best estimate of the geometric mean blood lead concentration 

for a typical child aged 6 to 84 months, assumed to reside at a given 

residence; 

(3) Provide a basis for estimating the risk of elevated blood lead (i.e., for 

exceeding a designated blood lead concentration of concern) for a 

hypothetical child of specified age with given site-specific residential lead 

exposure; 

(4) Provide a basis for estimating the risk of elevated blood lead 

concentrations among early pediatric populations in a given neighborhood 

by aggregating the individual residential risk estimates; 

(5) Predict likely changes in risk of elevated blood lead concentrations from 

exposure to soil, dust, water, or air lead following abatement actions 

designed to reduce exposure levels from one or more environmental 

media; 

(6) Provide assistance in determining appropriate soil or dust lead target 

cleanup levels at specific residential sites; 

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(7) Provide assistance in estimating blood lead concentrations associated with 

soil or dust lead concentrations at undeveloped residential sites that may 

be developed in the future. 

Each of these applications is discussed in more detail in Chapters 2, 4, and 5. The IEUBK 

model has been used for many purposes in addition to those for which it was originally 

intended. We are sure that the IEUBK model will continue to be used in many unintended 

and unexpected applications, just like any other new tool that has multiple uses. Some of 

these new applications are valid, others are demonstrably invalid, and the validity of many 

applications is simply unknown. 

The risk estimates are calculated for a hypothetical child or a hypothetical population of 

children who could be occupying the specific household at the time of the measurements or at 

some future time. The IEUBK model can therefore be used to estimate the risk of elevated 

blood lead even when there are no children currently living at a house, or if there exist only 

environmental lead data for the dwelling unit. The model does not require that a 

neighborhood or community blood lead study be carried out. The user should be aware that a 

site-specific risk assessment requires site-specific soil and dust concentrations, and some of 

the absorption parameters may depend on specific characteristics of the soil and dust at the 

site. The IEUBK model accepts user inputs for site-specific differences in bioavailability of 

lead in different media, and site-specific differences in environmental lead pathways for 

different lead sources. 

1.1.5 Validation of the IEUBK Model 

What does it mean to say that a computer simulation model is "valid"? In general, we 

interpret this to mean that: 

• the model is biologically and physically plausible and incorporates the best 

available empirical data on parameters; 

• the model uses numerically accurate algorithms and the accuracy of the 

computer codes for these algorithms has been verified; 

• the model provides some satisfactory empirical comparisons of model 

output with real-world data. 

We believe that the scientific basis and computational correctness of the IEUBK Model is 

sound, and that the IEUBK model provides valid prediction of observed blood lead 

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concentrations from representive populations of children with typical exposure. The 

empirical comparisons in which there are differences between observed and predicted blood 

lead concentrations underscore the importance of valid exposure scenarios as input. They 

also show the importance of valid blood lead data from truly representative population 

sampling methods when interpreting these empirical comparisons. 

1.1.5.1 The Model Is Biologically and Physically Plausible 

The parameters and equations used in the model are documented in the Technical 

Support Document: Parameters and Equations Used in the Integrated Exposure Uptake 

Biokinetic Model for Lead in Children. The exposure model component is based on data for 

human children in most instances, with lead exposures that are characteristic of children in 

the U.S. since about 1980. The ingestion parameters are based on surveys for drinking water 

and tap water (Ershow and Cantor, 1989), market basket estimates of dietary intake 

(Pennington, 1983; Gartrell, 1986), and on observational studies of soil and dust ingestion for 

children in the U.S. (Binder et al., 1986; Calabrese et al., 1989, 1992a,b, 1993; Davis et al., 

1990). While these studies have not resolved all of the uncertainty in childhood lead 

exposure, especially from sources such as lead-based paint, they have provided a much more 

realistic basis for quantitative modeling. The exposure component of the IEUBK model 

extends the UBK model assumptions (U.S. Environmental Protection Agency, 1989a) that 

have been reviewed by CASAC (1990). 

An absorption component was developed for the IEUBK model based on evidence 

discussed in Section 4.1. This evidence includes in vivo data in infant and juvenile baboons 

and human infants whose intake of lead is observed and known (Mallon, 1983; Sherlock and 

Quinn, 1986). The model has two modes for absorption, saturable and non-saturable. In the 

non-saturable mode, absorption of lead is a constant fraction of the total lead ingested for a 

specific medium. The saturable mode follows the Michaelis-Menten kinetics for saturable 

absorption as proposed by Aungst and Fung (1981). Development of the algorithm is also 

based on data from lead balance and feeding studies in human infants and children 

(Alexander, 1974a,b; Ryu et al., 1983, 1985; Ziegler et al., 1978). 

The compartmental structure of the earlier biokinetic model is based on compartmental 

models for lead in adults as discussed in detail in the Air Quality Criteria Document for Lead 

(U.S. Environmental Protection Agency, 1986). The model was verified and extended based 

on studies in infant and juvenile baboons (Mallon, 1983) whose age (5 to 26 months) and size 

(2.5 to 6 kg) are only slightly smaller than those of human children. The biokinetic 

distribution and elimination parameters use ratios of lead concentrations in tissues and blood 

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following chronic exposure. The ratios of lead concentrations in tissues of human children 

from autopsy data (Barry, 1975, 1981) were used to adjust the baboon's biokinetic 

distribution parameters to human infants and children (Harley and Kneip, 1985). The 

biokinetic parameters for baboons were re-estimated using the compartmental structure of the 

current IEUBK model (Marcus, 1992). The tissue-to-blood concentration ratios from the 

human child autopsy data were incorporated in the IEUBK model, assuring complete 

consistency with the best available data. 

1.1.5.2 The Model Is Computationally Accurate 

The IEUBK model uses a fast and accurate one-step numerical integration method 

known as 'backward Euler', with user-adjustable time steps to verify numerical accuracy of 

the solution. Coding of the model equations was verified by a separate recoding of the model 

in another programming language. Independent code verification will be described in 

forthcoming Technical Memoranda (see Section 1.2.2). 

1.1.5.3 Empirical Comparisons of the Model 

Comparison of the IEUBK model output with empirical human blood lead data has two 

requirements. The first requirement is that the child's total lead exposure is completely and 

accurately characterized by the empirical data, including site-specific data on environmental 

lead concentration, media ingestion, and bioavailability. The second requirement is that the 

blood lead data from the field study are accurate and typical for that exposure scenario. A 

typical child may not have the exposure described by the measured and default parameters of 

the model, or a child may also respond atypically to the measured and default parameters. 

The solution is to find the correct set of parameters (measured or site-specific alternatives to 

default) that describes the child's site-specific exposure or response to exposure. 

Environmental lead concentrations and blood lead measurements are subject to 

measurement errors such as repeat sampling variability and analytical error. Without careful 

attention to quality assurance/quality control (QA/QC) procedures, there may be systematic 

biases in blood lead measurements. The results of the blood lead field study may also differ 

from the model predictions for typical children if the blood lead sample is not representative 

of the population being sampled. 

Validation by empirical comparisons with paired data sets of good quality is an ongoing 

process. In earlier versions of the model, empirical comparisons indicated satisfactory 

agreement between observed and predicted blood lead concentrations. Several data sets have 

been identificed that are of adequate data quality for evaluating the validity of the IEUBK 

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Model, and more data sets are expected to become available in the future. The Field Study 

Data Set Comparisons document referred to in Section 1.2.2 will discuss the results of these 

analyses. Comparisons of empirical data with the IEUBK model require appropriate sitespecific exposure scenarios, valid assumptions about bioavailability, and demonstrated 

representativeness of the sample of children recruited into the study in relation to the target 

population from which they were drawn. 

Our preliminary analyses of several data sets so far indicate that the model satisfactorily 

predicts blood lead concentrations for the overall sample populations in specific 

neighborhoods. Further analyses will be needed to determine if empirical comparisons are as 

strong for subpopulations defined by factors such as differences in age, differences in contact 

or behavior that affected the amount of soil ingested, suspected or possible differences in 

bioavailability, differences in contribution of soil to household dust, and identifiable biases in 

recruitment of children. More extensive evaluation of these data sets will be described in the 

Field Study Data Set Comparisons document described in Section 1.2.2. 

Careful determinations should be made by users with regard to how well default values 

specified by this manual for key exposure and demographic parameters apply to the particular 

sample of children (or subpopulations) being evaluated. Appropriate adjustments made in 

pertinent default values may notably improve the fit of the model to empirical data. We 

caution the user not to arbitrarily select alternate values for the default parameters, but rather 

to obtain site specific or population specific data on important parameters. 

1.2 ORGANIZATION OF THE MANUAL 

1.2.1 Increasing Levels of Guidance and Technical Assistance 

This manual is designed to provide you with the information you need at several levels 

of detail. The further you read into manual the more specific guidance you will find for 

using the model. By the time you have finished reading Chapter 1, you should have a general 

understanding of how the model works and what it can do. You may want to install the 

model and then work your way through Chapter 2 as you become more familiar with each 

feature of the model. Instructions for installing the model are found in Section 2.4. 

As you explore the various features of the model, you will become familiar with the 

menus and their options. An overview of the menu system is in Section 2.1, and a detailed 

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description of these menus can be found in Section 2.2. This is the section that the novice 

user will want to follow closely. In a guided tour through the menu system, you will find 

that each menu option becomes a part of the process of constructing a model "run," and that 

these runs may be as simple as determining the blood lead concentration using only default 

exposure conditions, or as complicated as neighborhood risk estimation calculated as the sum 

of individual risks. Many of these options were suggested by comments received during the 

extensive review of drafts of this Guidance Manual. 

As you begin to apply the model to a specific risk assessment situation, you will find 

that Section 2.3 contains detailed recommendations for building an exposure scenario. This 

section also contains a helpful worksheet for planning model runs. Follow this section 

closely, as it contains many helpful suggestions on the appropriate use of the model, as well 

as warnings of improper applications. In Chapter 4, you will find a detailed discussion on 

assessing the relationship between soil/dust lead and blood lead. This chapter also describes 

the biokinetics of the model and specific issues in the use of the model for the ingestion of 

paint chips. If you need more help, turn to Chapter 5, where several specific examples are 

available to guide you through some of the more complicated procedures. As you become 

more experienced, you will find Chapter 3 a quick and ready reference to the various menu 

options. This chapter also contains a comprehensive review of default parameters. 

1.2.2 Additional Documentation 

Additional technical documents are or soon will be available to supplement the IEUBK 

Model and this Guidance Manual. These are: 

• Technical Support Document: Parameters and Equations Used in the 

Integrated Exposure Uptake Biokinetic Model for Lead in Children—a 

description and documentation of all equations and parameters in the model; 

• Field Study Data Set Comparisons—a description of several validation 

exercises that have been or will shortly be carried out; 

• Sampling Manual—approaches and protocols for environmental and 

biological sampling for collection of data compatible with the IEUBK 

Model; 

• Technical Memoranda—occasional technical updates that will be released to 

explain some features in greater detail or to alert the user to possible 

misapplications of the model. 

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1.3 GETTING READY TO USE THE MODEL 

1.3.1 Preparing a Site-Specific Exposure Scenario 

The use of the IEUBK model requires input data that are appropriate to the site(s) and 

subject(s). The most convenient way to do this is to construct a multi-media, site-specific 

exposure scenario using the exposure scenario worksheet (Figure 2-11; see Section 1.4.3). 

For most assessments of lead-contaminated soils, the minimal site-specific data are the 

soil lead and indoor dust lead concentrations for the residential exposure unit. Additionally, 

it would be helpful to include estimates of specific exposures from diet, drinking water, air, 

maternal exposure, or other sources that could replace the default exposure parameters 

believed to be of concern at the particular site. 

There may be potentially important differences among sites, and predictions of blood 

lead values are expected to become more accurate as more site-specific data are added. 

Children at highest risk are those with the highest exposures to some lead-containing 

medium. Data should be collected at a site so as to identify locations in the residence or 

community where young children may be exposed to elevated levels of lead in soil, dust, 

water, or air. Household-level data are useful because proposed soil, dust, and paint 

abatements are usually based on the house and yard as the most likely sources of lead 

exposure in preschool children. High exposures from lead in the household water 

distribution system are also possible, and this source has been identified in some childhood 

lead poisoning cases (Cosgrove et al., 1989). The preferred level of environmental input data 

for the model can be derived from a comprehensive multimedia household environmental lead 

study. 

The households studied should be representative of housing or sites where young 

children currently reside, as well as the places where young children may live in the future. 

In many applications, you will also need to include existing homes not occupied by children. 

These can usually be addressed in the same manner as housing currently occupied by 

children, using specific measurements of various environmental media lead concentrations. 

Risk assessments addressing as yet unbuilt housing should use existing residential site soil 

concentration data. 

Predictions of blood lead concentrations may improve with better information on lead 

concentrations where the child spends time during the day, or on child-specific behavior. 

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Activity pattern analysis, based on data taken from questionnaires and family interviews, can 

be useful in identifying children currently at risk, and in determining site-specific differences 

in behavior or access to lead sources that may differ in bioavailability. Public education and 

parental awareness of lead hazards may reduce the amount of lead in soil and dust ingested by 

the child, and quantitative studies of the effects of such actions are currently in progress. 

Exposure of children in day care centers, playgrounds or open areas may substantially 

affect total exposure to lead when potential lead exposures in such areas are high. These 

cases need to be considered in site risk assessment. The IEUBK Model allows dust and 

drinking water ingestion components to be separated into household and non-household 

sources by allocating a percentage of dust and water intake outside the home to sources with 

other concentrations. Time-weighted average air lead exposures are believed to be adequate 

indices of lead intake by inhalation in home and non-home settings under most circumstances 

and are used in the model. However, there is presently little information on the use of timeweighted averages for ingestion of soil, dust, or water away from the home. Soil and dust 

ingestion depends on children's activities, on hand-to-mouth behavior, and on intensity of soil 

contact related to sources and pathways away from home. 

In addition to exposure, the IEUBK Model also allows site-specific information on the 

bioavailability of lead from various sources to be taken into account. Bioavailability 

describes the relationship between the potentially available lead intake from environmental 

media and the amount of lead entering the body through the lungs or the gut and then into 

systemic circulation. 

You should be alert to the possibility that there may be site-specific differences in 

bioavailability of lead at different sites, particularly with respect to soil and paint. Some 

factors that may affect bioavailability include chemical speciation of lead in soil or paint, size 

of particles, mineral matrix of the particles, and whether the particles are likely to be ingested 

by the child along with meals or on an empty stomach. These are discussed in Section 4.1. 

Many of the issues are subtle and should be referred to the EPA Technical Review 

Workgroup for Lead. 

In some cases, relatively non-available environmental lead in soil or paint can be 

converted into readily available lead particles in household dust by physical and chemical 

processes in the environment. A housing unit with lead in paint or soil will continue to 

generate household dust lead exposure as long as paint deteriorates or is disturbed by 

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remodeling, and as long as outside soil and surface dust are moved into the house by pets and 

by human activities like gardening and remodeling. 

The model default value for the Geometric Standard Deviation (GSD) (reflecting 

variability among individuals who have contact with a fixed lead concentration) is based on 

analyses of data from neighborhoods having paired sets of environmental concentration and 

blood lead data. The recommended default GSD of 1.60 is believed to be very widely 

applicable. Only when reliable site-specific paired data from a sufficiently large study are 

available, should the substitution of a site-specific GSD be made using guidance given in 

Section 4.2. 

1.3.2 Understanding How the Biokinetic Component of the Model Works 

The general term "biokinetic" is used to describe the movement of lead through various 

parts of the human body as a kinetic process. Current blood lead concentrations depend on 

prior exposure history as well as present exposure. With constant lead exposure, a near 

steady-state blood lead concentration level is achieved because there is a dynamic nearequilibrium between lead moving out (from blood plasma to peripheral tissues and through 

excretory routes), and lead moving in (to plasma from gastrointestinal uptake and 

remobilization into plasma from peripheral tissues and long-term bone storage). 

The IEUBK Model assumes that skeletal lead turnover occurs relatively more rapidly in 

children than in adults. The lead in a child's blood is thus a mixture of lead taken up from 

recent environmental exposure and lead released from skeletal stores that reflect historical 

exposures. However, the faster turnover time assumed for children compared to adults 

implies that the lead burden in the skeleton is a smaller fraction of total body burden in 

children than in adults. The skeletal contribution to blood lead thus increases as the skeletal 

fraction of total body burden of lead increases. 

The blood lead concentrations in children achieve nearly a steady state relationship with 

exposure within a period of months after changes in exposure. The situation in children is 

more complicated than in adults because the kinetic parameters also change with the child's 

growth and with changes in behavior that affect lead intake, absorption, distribution, and 

elimination. The model is adequate to estimate childhood blood lead concentrations in nearequilibrium or in slowly changing exposure settings, as may be attained some time (months) 

after abatement occurs. The gradual phase down of lead in gasoline would be an example of 

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changes that occurred slowly enough in most urban areas to permit accurate modeling of 

blood lead concentration changes accompanying the air lead concentration changes. 

1.3.3 Understanding Limitations of the Model 

The IEUBK Model is designed to evaluate relatively stable exposure situations, rather 

than rapidly varying exposures. The model does not report each iterative calculation; rather, 

it reports one-year average blood lead concentrations. Because the IEUBK Model allows 

changes in exposure to environmental lead concentrations only at one year intervals, and 

provides output at only one year age intervals, changes in exposure are smoothed over one 

year. The model cannot be used to predict the effects of short term exposure episodes, such 

as exposure over a few days or weeks to lead dust and airborne particles that may be 

generated during lead paint abatement. The IEUBK Model should provide reasonable 

accuracy for blood lead concentration prediction as long as the changes in these 

environmental lead concentrations can be approximated by annual average values. 

The model is intended to describe a single residential-level exposure setting. The 

dwelling unit could be a detached single-family home, a separate home in a multiple-unit 

building such as a row house or duplex, or an apartment in a multiple-unit building. There is 

an implicit assumption that the input parameters characterize long-term residential exposure 

scenarios in such settings. While exposure changes daily in response to changes in the 

child's diet and activity, there is presumably a true mean exposure level that can, in principle, 

be estimated from real-life samples. For this reason, the IEUBK model allows changes in 

air, food, dust, and soil lead exposure input parameters only at 1-year intervals. Although 

water lead exposure could, in principle, be handled in similar detail, the IEUBK model does 

not allow annual changes in drinking water lead during the model run. The IEUBK model 

includes some capabilities for dealing with lead exposures outside the home, such as by use 

of separate dust ingestion parameters and concentrations at day care centers, schools, and 

secondary residences. 

We recommend using a simple average or arithmetic mean of soil lead concentrations 

from a representative area in the child's yard, and an average of dust lead concentrations 

from representative areas frequented by children inside the house. This rationale is 

appropriate for areas that are sufficiently small so that any part of the area may be accessible 

to a typical child living at a random residence located within the area. 

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The IEUBK model calculates blood lead and tissue lead burdens for all ages from 0 to 

84 months. However, the blood lead concentrations in children less than 6 months of age 

will still be affected by pre-natal lead exposure and are likely to show little influence from 

exposure to soil, dust, and paint, which are the media currently of greatest interest. The 

results of the model simulation are therefore not reported for children younger than 6 months. 

There are many reasons why individual blood lead concentrations may differ from the 

predicted geometric mean blood even though the predicted mean accurately describes the 

population. Some of the components of individual differences are discussed in Section 4.2. 

The GSD is the only parameter in the model that characterizes the combined variability in 

blood lead attributable to inter-individual differences and "random" temporal variability in 

absorption and biokinetics, "random" behavioral changes and inter-individual differences 

affecting ingestion rate, and measurement errors in environmental lead concentration. The 

strength of this approach is that GSD estimates are based on empirical data on the variability 

of blood lead levels in children exposed to similar concentrations of lead. Other approaches 

to evaluating the effects of variability, such as Monte Carlo simulation, were deferred for the 

present version of the IEUBK Model, because they demanded excessive computation and 

require much greater amounts of model input data. Monte Carlo methods, however, are still 

being evaluated as a possible enhancement of the IEUBK model, as discussed in Section 1.5. 

1.4 RUNNING THE MODEL 

1.4.1 Your Responsibilities 

The IEUBK model provides a great deal of flexibility in describing site-specific or agedependent exposure scenarios. The price for this level of flexibility is that no exposure 

scenario is appropriate for every application of the IEUBK model, and this is particularly true 

of the "default" parameters. The responsible use of the IEUBK model requires input data 

that are appropriate to the site(s) and subject(s). The most convenient way to do this is to use 

the exposure scenario worksheet (Figure 2-11; see Section 1.4.3). 

The most sensitive parameters for most applications involving soil lead exposure are the 

soil-to-indoor dust transfer coefficient, the soil and dust ingestion parameters, the soil lead 

absorption fraction, and the Geometric Standard Deviation. You should always review these 

parameters. 

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Factors affecting transport of soil lead into household dust should be noted when 

appropriate. For example, houses with very small grass-covered yards are likely to have a 

smaller contribution of the yard's soil lead concentration to household dust lead concentration 

than houses with large yards, no grass cover, and fine uncompacted surface soils that are 

easily blown or carried into the house by humans and outdoor pets. While the concentration 

of lead in exterior dust derived from the soil may be a useful measure of exposure, these data 

are not usually available because exterior surface dust samples are not usually collected. You 

are always responsible for the decision to use default values in place of either measured dust 

lead concentrations or dust lead concentrations estimated from soil lead concentrations. 

The proportion of intake in the form of soil vs. dust should be considered carefully, as 

there may be differences in the bioavailability of lead in soil vs. lead in house dust even when 

much of the dust is derived from soil. In spite of considerable efforts to determine the 

ingestion intake of soil and dust by children, these values are still subject to uncertainty. 

Site-specific data on soil ingestion by children are rarely available, but would be valuable in 

modeling site-specific exposure to lead. Only limited information is available about the 

effects of the child's micro-environment on soil and dust ingestion, with evidence suggesting 

much larger intakes of soil for children in intrinsically dirty environments such as 

campgrounds, and lower soil intake for children who spend much of their time in cleaner 

environments such as day care centers. 

You are responsible for the choice of non-default bioavailability parameters. 

Bioavailability parameters may differ among sites. Non-default bioavailability parameters 

may be justified by experimental studies with the actual site materials, assessments of other 

sites with similar materials, or site specific information on properties of particles that may 

affect bioavailability. 

The Geometric Standard Deviation is not considered a highly site-specific parameter, 

and should normally be kept at its default value of 1.60. If you use some other value, you 

should document the reasons for this modification, since risk estimates are typically very 

sensitive to the GSD value used. 

1.4.2 Exploring Model Options 

The IEUBK model has a large number of options. You are encouraged to explore these 

options before doing any substantive analyses, because there are often several alternative 

methods that can be used to obtain model outputs. These options are identified in Chapter 2. 

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They include alternative source menus for soil and dust lead, dietary lead, and lead in 

drinking water. The soil/dust lead menu includes options for air-to-dust and soil-to-dust 

transfer coefficients, as well as for non-household sources. 

There are options beyond single runs of the model. These include multiple runs for 

overlay plotting of probability curves, for plotting blood lead vs. environmental media lead 

concentration, and for multiple runs (batch mode input) for each of a group of individual 

children of different ages using child-specific data. 

The multi-media bioavailability menu includes options for changing the passive vs. 

facilitated absorption of lead from all media. The half-saturation uptake, a parameter that 

determines the extent of non-linear or saturable absorption, may also be changed from the 

normal default value of 100 Fg Pb/day. 

Run options include the choice of an iteration time step. With low exposure and no 

year-to-year change in concentration, as used in the "Default" option, there should be no 

differences in output using other iteration time steps. Differences in blood lead of a few 

percent may occur with higher and rapidly changing exposures. For a single run, almost any 

PC (XT or later) will produce a solution within 60 seconds, even without a math coprocessor, 

with the default iteration time of 4 hours. However, with a batch mode input file of several 

hundred records, the simulation run may take many hours. In this case, you may select a 

longer iteration time and speed up the run for a preliminary analysis. If you use a longer 

time step, you should verify accuracy using records with high exposure or large changes in 

exposure. 

1.4.3 Documentation of Input Parameter and Data Files 

By reviewing every adjustable parameter in the model and noting which ones have been 

modified in a particular run, you have a permanent record of the input. An electronic copy 

of the exposure input parameters can be made using the parameter SAVE option. Distinctive 

names for parameter files ([name].SV3), input data files ([name].DAT), simulation run files 

(RESULTS.TXT), batch mode output files ([name].TXT and [name].ASC), probability plot 

overlay files ([name].LAY) and blood lead vs. media concentration files ([name].MED) may 

be used to document input specifications as well as output. 

The worksheet provides a convenient format for noting reasons for use of non-default 

parameters, or justification for use of default parameters. For example, soil lead 

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concentrations and dust lead concentrations could be measured values at each house. 

Repeated values of household data would be used to weight the statistical results from batch 

mode files. Missing value imputation methods should be identified, for example, "KID ID = 

17,22,35, missing dust lead concentration estimated by PbD = 180 + 0.28 * PbS." This is 

critical information in allowing other users to reproduce your results (including yourself, 

since it is unlikely that most users will be able to recall over one hundred model parameters 

after the passage of some months or years). 

1.4.4 Documentation of Model Output 

1.4.4.1 Selecting Output Alternatives 

Results of IEUBK model simulations may be saved in several forms. You should select 

in advance the most useful of these forms, since the results of some interactive simulations 

cannot be recovered once you have bypassed the opportunity to save the results. Choices are: 

(1) A sequence of single simulation runs. Sequential runs can be interactively 

appended to the file named RESULTS.TXT. The average of the 

geometric mean blood lead concentrations for children in sequential 

one-year age intervals, the input concentrations for several media, and the 

media-specific daily lead uptake for each year are saved. You must use 

the "Save" option at the end of each run to be saved, but this allows you 

to drop results from non-informative runs rather than save them. 

(2) A sequence of graphics overlay simulation runs. The multiple plot option 

saves input data for blood lead probability plots for a range of evenly 

spaced media lead concentrations. For example, you may generate plot 

data for soil lead concentrations of 250, 500, 750, and 1000 ug/g, for 

children of ages 12 to 24 months. The data in the [name].LAY overlay 

file includes the geometric mean blood lead for children in the age range, 

the lead concentration in soil and in other media. The actual plots of 

probability density or cumulative distribution functions depend on the 

GSD value selected, and these plots include the probability of exceeding 

the user-specified LOC for use in risk estimation. Probability plots may 

be printed on standard laser printers. 

(3) A sequence of blood lead vs. media lead simulation runs. The media 

range option saves input data for blood lead vs. media lead plots for a 

range of evenly spaced media lead concentrations. For example, you may 

generate plots of blood lead vs. soil lead concentrations smoothly 

interpolated from calculated values at 250, 500, 750, and 1000 ug/g, for 

children of ages 12 to 24 months. The data in the [name].MED overlay 

file includes the geometric mean blood lead for children in the age range 

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at the selected media lead concentrations, the lead concentration in soil 

and in other media. Plots may be printed on standard laser printers. 

(4) Batch mode simulation runs. The batch mode option requires an input 

data file, as described in Chapter 2. Output consists of user-named files 

[name].ASC and [name].TXT that contain predicted blood lead 

concentrations for each case or record (child) in the input data file. The 

output files also document the missing value imputations when some of the 

input data on residential lead concentrations in air, water, soil, or dust are 

missing. The files may be used as input for the statistical analysis 

programs in the companion PBSTAT program, which produce statistical 

and graphical comparisons of the observed and predicted blood lead 

concentrations. 

1.4.4.2 Understanding the Output 

You should carefully review the output options described in Section 1.4.4.1. Each 

option allows you to examine a different aspect of the IEUBK simulation. The numerical 

simulation component of the IEUBK model produces an estimate of a geometric mean blood 

lead concentration for children of a given yearly age. This is the average of the estimates for 

children during that one-year interval. The IEUBK model arrives at these estimates by 

calculating at each time step an updated estimate of all compartment lead masses, or 

equivalent tissue lead concentrations. The update algorithm combines uptake of lead from the 

environment with all of the movements of lead into each compartment from another 

compartment, or out of each compartment, either into another compartment or by elimination 

from the child's body. In this version of the IEUBK model, the output consists of the daily 

uptake rate (intake rate times fraction absorbed) for each medium, and the blood lead 

concentration, as annual averages. 

The output from a single simulation run may be displayed in several forms. Most users 

wish to see the variability associated with a predicted blood lead concentration. This range 

can be demonstrated graphically by selecting the intrinsic variability GSD and then plotting a 

cumulative probability distribution. The range of plausible blood lead values may be 

determined graphically as defined by upper and lower percentiles of the distribution. For 

example, the 5th and 95th percentiles of the distribution will include 90 percent of the 

children with the given site-specific or household-specific exposure scenario. Since 

"plausible range" requires a subjective choice of percentiles, you are free to choose any 

appropriate values. Since the predicted geometric mean blood lead concentration is based on 

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an a priori mathematical simulation and not on a data-driven statistical estimate, this plausible 

range should never be considered as equivalent to a confidence interval. 

The other output characteristic that many users wish to see is the estimated probability 

of exceeding the specified blood lead level of concern, corresponding to the given exposure 

scenario or scenarios (for multiple runs in a given medium). This also requires a GSD value. 

This probability may be interpreted as the percentage of children with the given householdspecific exposure scenario who are expected to exceed the level of concern. If applied to a 

single site or residence, it may also be interpreted as the probability of exceeding the level of 

concern for any single child who may reside at that site in the future. 

1.4.4.3 Interpreting the Output and Communicating the Results 

The model calculates the probability that a blood lead concentration derived from the 

model's specified parameters will exceed a level of concern specified by the user. There are 

two valid interpretations for the output: 

(1) The output of the model may be considered to be the best estimate of a 

plausible range of blood lead concentrations for a hypothetical child with 

a specific lead exposure scenario. The range of values is centered on the 

geometric mean blood lead concentration expected for a typical child with 

this exposure scenario. The upper tail of the probability distribution 

provides an estimate of the risk of exceeding some blood lead level of 

concern for a typical child of that age residing in the same household and 

with the same exposure history. 

(2) The output of the model may also be considered to be the predicted 

geometric mean blood lead of a population of children with the same lead 

exposure scenario, and the upper tail of the probability distribution to be 

the fraction of children exceeding the chosen blood lead level of concern 

when all of these children have the same exposure history. 

The array of applications for which the IEUBK model can be validly used is: 

A: One location 

A1: one living unit, one child; 

A2: one living unit, more than one child; 

A3: more than one living unit, more than one child, homogeneous media 

concentrations; 

B: Multiple locations, one neighborhood, homogeneous media concentrations 

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C: Multiple locations, one neighborhood, heterogeneous media 

concentrations; 

D: Multiple locations, more than one neighborhood, heterogeneous media 

concentrations; 

A single run of the IEUBK model is sufficient for categories A and B. A classification 

or disaggregation of the neighborhood into distinct exposure subgroups is required in 

categories C and D, with the possibility of different ingestion or absorption parameters for 

different neighborhoods in category D. Neighborhood-scale and community-scale risk 

estimation requires aggregating the risk estimates for individuals or subgroups. 

The differences between these levels is sketched in Figure 1-3. Category A requires 

calculating only a single blood distribution. Category B requires calculating a blood lead 

distribution for each child, but since each child of the same age has the same exposure 

scenario in category B, a single run of the model is sufficient to characterize risk for this 

subgroup. In category C, there are different exposure scenarios for each subgroup. Risk 

estimates must be calculated for each such subgroup, then added up across sites and children. 

The model output in category A: Single child, single site of exposure, includes a blood 

lead concentration, a distribution of blood lead concentrations, and a probability of exceeding 

the blood lead level of concern. Since children in environments with the same lead exposure 

may have a range of blood lead concentrations, we describe the likely variability in blood 

lead for a child with a given exposure scenario by a probability distribution. The predicted 

blood lead concentration is the geometric mean of the distribution of blood lead 

concentrations that may occur for a typical child with the specified exposure scenario. Risk 

is calculated from this distribution as the probability that a hypothetical child living at this 

site, with the specified exposure scenario, will have a blood lead concentration exceeding the 

blood lead level of concern. This single-child assessment is necessary in order to use the 

model to evaluate remediation options on a house-by-house or yard-by-yard basis. The 

single-child assessment also provides a criterion for model testing and validation using 

epidemiology data. 

The model output in category B: Multiple children, single site or equivalent sites of 

exposure, is the predicted blood lead concentration for each child as the geometric mean of 

the distribution of blood lead concentrations that may occur for each child with the specified 

exposure scenario. Risk is calculated by aggregating the calculated risk for each child as the 

percentage of hypothetical children living at this site or at these sites, with the specified 

exposure scenario, that will have a blood lead concentration exceeding the blood lead level of 

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A.

B.

C.

D.

Probability

Blood Lead

Child 1

Site 1

Child 2

Site 2

Child 3

Site 2 Site 3

Child 1 Child 2 Child 3 Child 4

Single child

Single site of exposure

Multiple children or population

Single site or comparable sites

Multiple children or population in neighborhood

Multiple sites with different exposures

Multiple children or population in heterogeneous community

or region, different neighborhood exposure scenarios

Figure 1-3. 

concern. 

important shift in interpretation of the output. 

There are situations in which a single site really can have multiple children of the same

age with the same exposure scenario. 

households with pre-school children of the same age. 

succeeding years by different families, each of which may have a pre-school child of the same

age with virtually the same exposure as occupants in other years. 

child or population exposure scenarios would be applied to a hypothetical population of

occupants.

Neighborhood-scale risk estimation is discussed in Section 4.2, with examples. 

model output in C: 

Categories of application of the IEUBK Model.

The calculation is exactly the same as the single-child assessment, but there is an

A single housing unit may be occupied by several

Rental properties may be occupied in

In general, the multipleThe

Multiple children, multiple sites with different exposure, cannot be
obtained by a single run of the IEUBK model. It is necessary to construct an exposure 

scenario for each distinct exposure subgroup in the population. For each child or exposure 

subgroup, risk is calculated in a single run of the IEUBK model with the specified exposure 

scenario. The risks for each exposure subgroup are aggregated across all subgroups, 

weighted by the number of children with that exposure scenario or by the percentage or 

likelihood of the exposure scenario. 

There is no one-step method by which neighborhood-scale risk estimation can be done 

using this version of the IEUBK model. The problem of risk estimation for children in a 

large community or a region is even more difficult when different subgroups of children may 

have very different exposure scenarios, including differences in behavior that affect ingestion, 

and differences in lead absorption due to behavioral or nutritional differences. 

A common misinterpretation of the IEUBK Model is that it predicts community 

geometric mean blood lead and the fraction of children at risk when the input is the mean or 

geometric mean of household-specific environmental lead concentrations. That mis-step can 

be misleading, particularly when the environmental variables have a wide distribution among 

the neighborhoods of the community. This misinterpretation is especially dangerous for postabatement settings intended to eliminate the higher exposures when there are multiple 

exposure media. A correct approach requires applying the model to each individual home or 

site using the lead concentrations seen at that site and combining these results as an aggregate 

of sites in several neighborhoods to form an estimate of community risk. A second useful 

approach is based on subdividing a community into neighborhoods and clusters of residence 

units with similar media lead concentrations. Specific information on building appropriate 

neighborhood exposure scenarios is given in Section 2.3, Building an Exposure Scenario. 

Examples are provided in Section 4.2. 

We should emphasize that the IEUBK model is intended to provide a best estimate of 

geometric mean blood lead. The IEUBK model is not intended to be used in a worst-case 

scenario, as the model does not apply any uncertainty factors or modifying factors in making 

risk estimates. If, as usual, there is some uncertainty about model parameters, these can be 

evaluated using sensitivity analyses. Remember that you are responsible for documenting 

plausible non-default values. 

Uncertainty about parameters is not the same as the intrinsic variability in 

environmental data and blood lead responses. The components of variability are discussed in 

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Section 4.2 on the blood lead Geometric Standard Deviation (GSD), which plays a critical 

role in risk estimates. 

1.5 REFINEMENTS AND ENHANCEMENTS 

The biokinetic component of the IEUBK model is based on an age-dependent 

compartmental model with identifiable physiological compartments: red blood cells, plasma 

and extracellular fluids, kidney, liver, other soft tissues, trabecular and cortical bone (Figure 

1-1). There are many compartmental models in the literature; some with fewer compartments 

(Rabinowitz et al., 1976), others with many more compartments (Leggett, 1993). The 

Technical Review Workgroup for Lead was aware of important research in the development 

of physiologically-based pharmacokinetic (PB-PK) models for lead in humans, primates and 

rats that took into account the slow diffusion of lead through the bone matrix (O'Flaherty, 

1992a,b,c, 1993a,b). However, the Workgroup chose to develop a compartmental model that 

uses transfer times or transfer rates between compartments instead of physiologically based 

compartmental coefficients. The transfer rates can be estimated from data in non-human 

primates, especially the studies on infant and juvenile baboons that were done at New York 

University (Mallon et al., 1983; Harley and Kneip, 1985). 

The IEUBK biokinetic model was based on: 

(1) empirical kinetic data on blood lead in baboons of similar weight and 

developmental stage to human infants and young children; 

(2) kidney, liver, tibia and femur lead concentrations in baboons after the end 

of the lead exposure study; 

(3) autopsy data for lead levels in young children who died from causes not 

related to lead exposure; 

(4) extrapolations from studies in human adults; 

(5) lead feeding and lead balance studies in human infants. 

There is, in principle, a degree of similarity between these approaches, since the 

compartments in the IEUBK model are defined by real anatomical and physiological 

properties. The transfer times from the PB-PK model can be calculated from blood flow 

rates to organs and tissue groups, volumes of these organs, partition coefficients across 

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membranes, and solid state diffusion coefficients for the bone matrix. The principal 

difference between the biokinetic components of the IEUBK and PB-PK models is that, in the 

absence of suitable physiological data, empirical data were used in estimating transfer times 

in the IEUBK model. Future development of the IEUBK Model is expected to continue in 

the direction of physiologically based biokinetic components similar to PB-PK models. 

Many users have expressed interest in tools that allow a more detailed investigation of 

the effects of non-environmental variability on the distribution of blood lead concentration. 

The Monte Carlo approach would allow every parameter in the model to be assigned a 

random variation at every iteration of the computation. For example, each parameter could 

be multiplied by a random factor (mean value 1) at every iteration. This would require that 

adequate data would be available to support the input distributions. An extremely large 

amount of computing would be necessary. A substantial amount of additional study is needed 

before Monte Carlo methods can be added to the IEUBK model. 

The IEUBK model currently evaluates children from birth to age 84 months. Many 

users have requested extension of the model to other populations, including older children 

and adults, with emphasis on populations at special risk. Both the physiological and 

biokinetic parameters of adults are at least as well known as those of children, with the 

possible exception of lead distribution within the human maternal-fetal unit. Transfer of lead 

from the mother to the neonate during lactation would also be of interest. 

1.6 GETTING MORE HELP 

As scientific knowledge advances, this Guidance Manual will be updated and revised. 

If you have questions regarding the site-specific application of the IEUBK Model, you may 

direct your inquiries to the appropriate EPA Regional Toxics Integration Coordinator. 

Comments on the technical content of the manual or suggestions for its improvement may be 

brought to the attention of members of the EPA Technical Review Workgroup for Lead listed 

in the front of this document. 

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