United States National Center for EPA/600/R-05/102 

Environmental Protection Environmental Assessment October 2005 

Agency Research Triangle Park, NC 27711 

 

Guidance Manual 

for the 

All Ages Lead Model 

(AALM) 

Draft Version 1.05

Prepared by 

National Center for Environmental Assessment 

Office of Research and Development 

U. S. Environmental Protection Agency 

Research Triangle Park, N C 27711

Research and Development
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NOTICE 

The U.S. Environmental Protection Agency, through its National Center for Environmental 

Assessment at Research Triangle Park, produced this report. This document is a preliminary 

draft. It has not been formally released by the U.S. Environmental Protection Agency and 

should not be construed to represent Agency policy. It is circulated as a guide for reviewers of 

the model.
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TABLE OF CONTENTS

AUTHORS AND CONTRIBUTORS.......................................................................................... 5

LIST OF FIGURES ...................................................................................................................... 6

SECTION 1: INTRODUCTION ................................................................................................. 8

SECTION 1: INTRODUCTION ................................................................................................. 8

1.1 INSTALLATION.............................................................................................................................9

1.2 BACKGROUND AND BASIS FOR PARAMETER VALUES...................................................9

1.3 RUNNING THE MODEL.............................................................................................................10

1.4 A QUICK REVIEW OF THE MODEL ......................................................................................12

2: BUILDING THE MODEL RUN........................................................................................... 17

2.1. EDITING PARAMETERS ...........................................................................................................19

2.1.1. MEDIA EXPOSURES ...........................................................................................................19

2.2 EDITING EXPOSURE ACTIVITY PATTERNS .......................................................................28

2.3 SUMMARY AND CONCLUSIONS ............................................................................................28

SECTION 3: SPECIAL EXPOSURE FEATURES................................................................. 32

3.1 PICA EXPOSURE..........................................................................................................................32

3.2 DERMAL EXPOSURE..................................................................................................................32

3.3 HISTORICAL LEAD EXPOSURES............................................................................................33

3.4 MATERNAL EXPOSURE (Conceptual Design).........................................................................33

SECTION 4: ABSORPTION MODULE.................................................................................. 34

4.1 MODELING LEAD ABSORPTION ............................................................................................34

4.2 ABSORPTION OF INHALED LEAD..........................................................................................36

4.3 ABSORPTION OF INGESTED LEAD.......................................................................................37

SECTION 5: BIOKINETICS MODULE ................................................................................. 39

5.1 MODEL SETTINGS ......................................................................................................................39

5.1.1 PARAMETERS WITH EXPLICIT VALUES .....................................................................39

5.2 BIOKINETIC PARAMETERS....................................................................................................42

5.2.1 Pb DECAY RATE...................................................................................................................43

5.2.2 CORTICAL BONE TURNOVER. ....................................................................................43

5.2.3. TRABECULAR BONE TURNOVER RATE. .............................................................44

5.2.3 TRANSFER FROM CORTICAL SURFACE TO BLOOD PLASMA..........................46

5.2.4. TRANSFER FROM TRABECULAR SURFACE TO BLOOD PLASMA. ..............47

5.2.6 CORTICAL SURFACE TO VOLUME TRANSFER. ....................................................48

5.2.7 TRABECULAR SURFACE TO TRABECULAR VOLUME TRANSFER. .....................49

5.2.8 TOTAL TRANSFER FROM EXCHANGE BONE VOLUME. .........................................50

5.2.9. TRANSFER FROM THE EXCHANGE TO THE NON-EXCHANGE VOLUME. 50

5.2.10. TRANSFER FROM LIVER1.............................................................................................51

5.2.11 TRANSFER FROM KIDNEY1. .........................................................................................51
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5.2.12 TRANSFER FROM BLADDER TO URINE....................................................................51

5.2.13 TRANSFER FROM LIVER2..............................................................................................52

5.2.14 TRANSFER FROM KIDNEY2. .........................................................................................53

5.2.15 TRANSFER FROM FAST SOFT TISSUE. ......................................................................54

5.2.16 TRANSFER FROM INTERMEDIATE SOFT TISSUE. .................................................55

5.2.17 TRANSFER FROM SLOW SOFT TISSUE......................................................................56

5.2.18 TRANSFER RATES FROM BRAIN. ................................................................................57

5.2.19 DEPOSITION FRACTION IN URINE. ............................................................................58

5.2.20 DEPOSITION FRACTION IN BONE...............................................................................59

5.2.21 TRABECULAR BONE DEPOSITION FRACTION. ......................................................60

5.2.22 DEPOSITION FRACTION IN COMPARTMENTS WITHOUT AGE VARIABIL. ...61

5.2.23 DEPOSITION FRACTION FROM DIFFUSIBLE PLASMA TO FAST SOFT . .........62

5.2.24 DEPOSITION FRACTION FROM DIFFUSIBLE PLASMA TO INTERMEDIATE. 63

5.2.25 DEPOSITION FRACTION FROM DIFFUSABLE PLASMA TO SLOW SOFT. .......64

5.2.26 DEPOSITION FRACTION FROM DIFFUSIBLE PLASMA TO BRAIN. ..................65

5.2.27 COMPONENTS OF THE CIRCULATORY SYSTEM...................................................66

5.2.28 TRANSFER RATE FROM RBC TO PLASMA. ..............................................................66

5.4.29 AMOUNT OF BLOOD........................................................................................................67

5.2.30 CHELATION FACTORS 1,2,and 3. ..................................................................................68

SECTION 6. CONTROLLING THE MODEL OUTPUT...................................................... 69 

6.1. A SIMPLE CONFIDENCE TEST ...............................................................................................69

6.2. BIOKINETIC OUTPUTS.............................................................................................................71

6.2.1 TABLES...................................................................................................................................71

6.1.2 PLOTTING..............................................................................................................................71

6.1.3 EDITING THE CHART.........................................................................................................72

SECTION 7. 

REFERENCES.............................................................................74 
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AUTHORS AND CONTRIBUTORS 

Robert Elias, U.S. Environmental Protection Agency 

Brian Gulson, Macquire University, Sidney Australia 

Gary Diamond, Syracuse Research Corporation 

Ramon Olivera, Lockheed-Martin Information Technology 

Goeffrey Nonato, Lockheed Martin Information Technology 
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LIST OF FIGURES

Figure 1. Opening screen with NCEA Logo and disclaimer.....................................................................................10

Figure 2: Window with prompt to create a new study or open an existing study. ....................................................11

Figure 3. Drop Down window that allows the Modeler to customize three features of the program setup..............11

Figure 4: Primary Window - Modeler defines the individual by sex, life span, and time frame...............................12

Figure 5: Model component selection window. Click on exposure to run this portion of the model.......................13

Figure 6: Model status window. Select options to use historical data.....................................................................13

Figure 7: Retrieve model output file.........................................................................................................................13

Figure 8: Output data file in spreadsheet format. ....................................................................................................14

Figure 9: Primary Window with Male gender, End Date computation, and one day time step selected..................15

Figure 10. Drop-down window for resetting the model date......................................................................................16

Figure 11. Bar along top of screen with Tools option. ...............................................................................................18

Figure 12. Tool Selection Menu.. ...............................................................................................................................18

Figure 13. Drop down window to select the output parameters to be displayed........................................................18

Figure 14: Primary window with full specifications for model run, ready for entering exposure parameters...........19

Figure 15. Save Current Study ...................................................................................................................................19

Figure 16. Select Exposure Parameters to review and modify the exposure portion of the model.............................20

Figure 17: Exposure options group with Air component ready for review and modification.....................................21

Figure 18: Options for Dietary exposure. ..................................................................................................................22

Figure 19. Dietary exposure with garden fruits and vegetables.................................................................................23

Figure 20: Exposure options for dust exposure..........................................................................................................24

Figure 21: Drop Down window for the Dust component of Media Exposure. ...........................................................25

Figure 22: Window for the Dust component of Media Exposure................................................................................25

Figure 23: Window for the dust component of Media Exposure. ...............................................................................26

Figure 24: Window for the Water component of Media Exposure with the default option of Fully Flushed Water...27

Figure 25: Window for the Water component of Media Exposure with the options for Other Water Sources. ..........27

Figure 26: Drop down window for the Activity Patterns component of Media Exposure. .........................................28

Figure 27: Following set of the Exposure Scenario, the model run is initiated by checking the Exposure................29

Figure 28. Two files are available for review, *.mod and *.mpa. ..............................................................................30

Figure 29. Line by line output for the exposure module. *.mod .................................................................................30

Figure 30. Total exposure by age for each exposure category (*.mpa)......................................................................30

Figure 31: Exposure Model options with options to change internal exposure and growth parameters. ..................31

Figure 32: Window for the Pica component of Media Exposure................................................................................32

Figure 33: Window for the Dermal component of Media Exposure...........................................................................33

Figure 34. Schematic diagram of the Leggett Model..................................................................................................35

Figure 35: Drop down window for reviewing and revising........................................................................................36

Figure 36: Window for editing Absorption Parameters. ............................................................................................36

Figure 37: Drop down window for gastrointestinal absorption showing default values.............................................37

Figure 38: Plot of the default values for the gastrointestinal absorption fraction. ....................................................37

Figure 39: Default values for the gastrointestinal rate of movement function. ..........................................................38

Figure 40: Plot of the default values for the rate of gastrointestinal movement function...........................................38

Figure 41: Schematic Diagram of O’Flaherty Model. ...............................................................................................42

Figure 42: Window for editing the model settings.......................................................................................................41

Figure 43: Drop down window for editing the default Delta Step lengths. .................................................................42

Figure 44: Window for editing biokinetic parameters................................................................................................42

Figure 45. Schematic Diagram of Leggett Model.......................................................................................................43

Figure 46: Values for cortical bone turnover rate which decreases with age...........................................................44

Figure 47: Plot of default values for cortical bone turnover rate by age. ..................................................................44

Figure 48. Age-specific values for Surface to Volume in Trabecular Bone................................................................45

Figure 49. Plot of Trabecular Surface to Volume.......................................................................................................45

Figure 50: Values for trabecular bone turnover rate by age......................................................................................45

Figure 51: Plot of default values for trabecular bone turnover rate by age...............................................................46
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Figure 52: Dropdown window for editing the parameter for transfer from cortical surface to blood. ......................46

Figure 53: Plot of the default values for the parameter for transfer from cortical surface to blood..........................47

Figure 54: Drop down window for editing the parameter for the transfer rate for trabecular surface to blood. ......47

Figure 55: Plot of the default values for the transfer rate for trabecular surface to blood........................................48

Figure 56. Window for editing the value for transfer from cortical surface to volume. ..............................................48

Figure 57: Plot of the default values for transfer from cortical surface to volume. ...................................................49

Figure 58: Window for editing the values for transfer from trabecular surface to volume........................................49

Figure 59: Plot of the default values for transfer from trabecular surface to volume................................................50

Figure 60: Window for editing values for total transfer from the exchange bone volume. ........................................50

Figure 61: Window for editing values for total transfer from the non-exchange bone volume. ..................................51

Figure 62: Window for editing the values for the transfer of lead from the bladder to urine. ...................................52

Figure 63: Plot of the default values for the transfer of lead from the bladder to urine. ...........................................52

Figure 64. Age-related coefficients for transfer of lead from Liver2..........................................................................53

Figure 65. Plot of the transfer of lead from the liver 2 compartment.........................................................................53

Figure 66: Drop down window for editing the default values for the transfer of lead from the kidney......................54

Figure 67: Plot of the default values for the transfer of lead from Kidney 2 (From Kidney to Bladder). ..................54

Figure 68: Drop down window for editing the default values for the deposition fraction of lead in fast soft tissue.. 55

Figure 69: Plot of the default values for the deposition fraction of lead in fast soft tissue. .......................................55

Figure 70: Drop down window for editing the default values for the deposition in intermediate soft tissue.. ...........56

Figure 71: Plot of the default values for the deposition fraction of lead in fast soft tissue. .......................................56

Figure 72: Drop down window for editing the default values for the deposition fraction in slow soft tissue..............57

Figure 73: Plot of the default values for the deposition fraction of lead in slow soft tissue.......................................57

Figure 74: Drop down window for editing the default values for the deposition fraction of lead in the brain. ..........58

Figure 75: Plot of the default values for the deposition fraction of lead in the brain.................................................58

Figure 76. Deposition fraction in Bone. .....................................................................................................................59

Figure 77. Plot of Deposition Fraction in Bone. ........................................................................................................59

Figure 78. Bottom of biokinetic Parameters Window.................................................................................................60

Figure 79. Age-dependent Variables for Trabecular Bone Deposition Fraction. ......................................................60

Figure 80. Trabecular bone deposition fraction.........................................................................................................61

Figure 81: Plot of the default values for the transfer of lead from the liver...............................................................61

Figure 82. Age-dependent Variables for Diffusible Plasma to Fast Soft Tissue..........................................................62

Figure 83. Plot of the default values for the Diffusible Plasma to Fast Soft Tissue parameter..................................63

Figure 84. Age-dependent Variables for Diffusible Plasma to Intermediate Soft Tissue............................................63

Figure 85. Plot of the default values for the diffusible Plasma to Intermediate Soft Tissue parameter......................64

Figure 86. Age-dependent Variables for Diffusible Plasma to Slow Soft Tissue. ........................................................64

Figure 87. Plot of the default values for the Slow Soft Tissue Parameter. .................................................................65

Figure 88. Age-dependent Variables for the Deposition Fraction from Diffusible Plasma to Brain. .........................65

Figure 89. Plot of the default values for the Deposition Fraction from Diffusible Plasma to Brain parameter.........66

Figure 90. Age-dependent variable for the Transfer Rate from RBC. ........................................................................67

Figure 91. Plot of the default values for the Transfer Rate for RBC parameter.........................................................67

Figure 92. Age-dependent variable for total volume of blood (deciliters...................................................................68

Figure 93. Plot of the default values for the Amount of Blood parameter..................................................................68

Figure 94. Output with all default settings .................................................................................................................69

Figure 95. Total Blood lead with elevated dust lead exposure...................................................................................70

Figure 96. Using the Built in Graphic Feature. .........................................................................................................72
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SECTION 1: INTRODUCTION 

The purpose of the All Ages Lead Model (AALM) is to make available to the risk assessor a 

sufficiently complex, multi-compartment biokinetic model that predicts with reasonable 

accuracy the tissue concentrations of lead in humans and informs the modeler of the resulting 

changes in tissue concentrations that might occur over the lifetime of the modeled individual. 

The original model developed for this purpose, the Integrated Exposure Uptake Biokinetic 

Model for Lead in Children (IEUBK) met some of these objectives in that it is a multicompartmental model that predicts blood concentrations of lead in humans, but the IEUIBK 

model makes this prediction only through age six and provides no information on the tissue 

concentrations (White et al, 1998). The AALM accomplishes this objective by providing an 

Exposure and Absorption interface to a biokinetic model. 

This interface guides the modeler toward a thorough, accurate description of the total daily 

exposure to lead, calculating the amounts of lead absorbed. The model then offers a choice of 

two biokinetic models to determine how the lead is distributed to the key body tissues1

. These 

two models are referred to as the Leggett Model (Leggett, 1993) and the O’Flaherty Model 

O’Flaherty, 1998). One advantage of the Leggett Model is that it characterizes the distribution 

of lead based on the function of the human circulatory system, including the extracellular fluids. 

 Likewise, the Leggett model also recognizes the chemical relationship between Pb and Ca. 

especially in describing the complexity of the bone compartments. There are some deficiencies 

in the Leggett model that can perhaps be overcome by the use of the O’Flaherty model, and we 

expect to make this feature available in the near future. 

This document takes you step-by-step through the process of getting the AALM up and running 

on your computer. As with all software packages, expertise is achieved by trial and error, and by 

aggressively investigating all model features. You will find that by starting from the simplest 

case and moving systematically to the more complex applications, you will soon develop 

expertise that matches your interests. 

This Guide takes into account comments and suggestions from many competent reviewers, 

evaluators and experienced modelers. It is not intended as a primary source of information 

regarding the source code for the AALM model, which is documented elsewhere. That 

document identifies the inherent structure of the three components of the AALM: lead exposure 

(intake) model, lead absorption (uptake) model, and biokinetic distribution model. It documents 

how the software system was designed to implement these models and describes each of the data 

elements used by the system, the functional flow of data through the system and the interfaces 

between the components. 

Model development is not an easy effort. In addition to the science behind the process, there are 

also concerns about the development process itself. During the AALM development, which 

occurred over a period of approximately eight years, several symposia and workshops were held, 

including one on Model Validation (Elias et al, 1998). At that workshop, two papers have 

 

1 The O’Flaherty model is not fully implemented at this time. We expect to complete this task in the next few 

weeks. Meanwhile, if the O’Flaherty option is selected, the model will switch to the Leggett model and notify the 

modeler thereof. 
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provided significant guidance to this project: Oreskes: Evaluation (Not Validation) of 

Quantitative Models; and Mickle: Structure, Use, and Validation of the IEUBK Model. 

The development of a large modeling system such as this is an ongoing process. The current 

version will, hopefully, meet the needs of most modelers. But in the process of developing this 

model, the planners recognized several features that could be incorporated with minimal effort, 

given the successful completion of the basic model. Construction of these additional features 

has been initiated and is discussed in Chapter 4 of this document. Comments are most welcome. 

1.1 INSTALLATION

AALM requires Windows 95 or later (Windows 98, or Windows NT, Windows 2000, Windows 

XP). If you already have a previous review version of the AALM installed, the new version 

includes a user option to automatically uninstall the previous version. AALM is distributed as a 

bundled package that, when activated, will place all required files in a single directory with a 

default designation of C:\Program Files\AALM. The AALM program is installed with 

InstallShield using the Add/Remove feature of the Windows Control Panel. Thus, a new 

subdirectory called will appear in this directory after installation, and the All Ages Lead Model 

icon should appear on your opening window. Unless you designate otherwise, your project files 

will be stored in a subdirectory of this directory. One additional file, DEMO1.xal has also been 

installed to assist you in becoming familiar with the AALM. You will have an opportunity to 

access this file as you work your way through this manual. 

1.2 BACKGROUND AND BASIS FOR PARAMETER VALUES 

The purpose of the All Ages Lead Model is to mathematically provide an exposure, absorption, 

and biokinetic infrastructure that allocates, by simulation, the simultaneous distribution of 

absorbed lead in several major body components and thereby predict at any point in time the 

concentration of lead in these components. 

The All Ages Lead Model has about 190 parameters with assigned values that can be revised by 

the modeler to meet the description of a modeled individual designed by the modeler. All values 

for these parameters have default settings that permit the model to run to a conclusion, reaching 

an endpoint whereby the predicted outcome can be determined that is consistent with the 

modeled input. This means that the model will run in the default mode, and will produce 

reasonable results consistent with the default inputs. The modeler, therefore, has the option to 

change one or more of the input parameters and rerun the model to compare the new results with 

the default output, or to create and save another “default” model parameters consistent with the 

needs and requirements of his/her investigation. A companion document, the AALM Parameters 

and Equation Dictionary, describes these model components in greater detail. 
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The AALM default values for the biokinetic parameters are based on published experimental 

values or ranges of values used for the Leggett and O’Flaherty models. Many of these default 

values have no meaning or significance other than as a place holder for a value that may be 

assigned by the modeler. With few exceptions, there are no documented values that can be 

validated by reliable literature reports. Consequently, the modeler must always be aware of the 

need to review the results rigorously, and establish internal constraints that adequately bracket 

the desired objective. 

1.3 RUNNING THE MODEL 

After installation, click on the All Ages Lead Model icon to open the program. The NCEA logo 

(Figure 1) should appear with text disclaiming responsibility prior to official release. Click OK. 

 If you highlight box to “close the screen automatically”, the next time you run the model, this 

Logo screen will be displayed for about five seconds, then move on to the window in Figure 2. 

Figure 1. Opening screen with NCEA Logo and disclaimer 

This window gives you the option to create a new study or open an existing study. The default is 

to create a new study, but you may want to start your orientation with a demonstration study that 

will to provide you with a quick review of the model. 
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Figure 2: Window with prompt to create a new study or open an existing study. Your new 

file will be saved in a subdirectory of the AALM Program directory. You can 

change this default directory by clicking on Tools at the top of the screen, then 

Options. Type the new directory and any subdirectories in the window labeled 

Data.

 

Figure 3. Drop Down window that allows the Modeler to customize three features of the 

program setup. 

The features of the Startup Preferences window are: The automatic closing of the opening screen 

after a 5 second delay, the choice to display or not to display the Select Action dialog box after 

the opening screen, and the opportunity to change the directory where the user-created output 

data files are stored. This last choice, which is, by default, the AALM subdirectory of the 

C:\Program directory, is especially important if the Modeler is accustomed to backing up only 

the files located in the C:\Documents and Settings directory, in which case, the AALM output 

files would not be saved. This Window may be accessed from the upper bar below the Screen 

Title by selecting the “Tools” option. 
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1.4 A QUICK REVIEW OF THE MODEL 

If this is your first time using the model, perhaps it would be a good idea to begin with a 

demonstration file that will provide the required settings you will need to get started. Select 

‘Open an existing study’ from the Select Action window, then choose Demo1.xal to get started. 

Follow these steps to run through the model. (You can return to this place in the Guidance 

Manual to continue your review of the model features): 

If you installed the program according to the instructions in Section 1.1, you should be able to 

select Demo1.xal from the File Open window. Click on the Open button to get the next screen, 

which is the hub of the model and is referred to in this manual as the Primary window. From 

here you can specify the input parameters for the model using the options on the screen. First 

note that this is a typical Windows® screen with drop down menus for many Windows® 

functions at the top. The model will use the default screen color format you have selected for 

your computer. 

Figure 4: Primary Window - Modeler defines the individual by sex, life span, and time 

frame, and accesses the parameter definition windows. 

These settings will run the model using the default settings for the full lifetime of the 

hypothetical person that you define by entering or changing the appropriate values in the 

exposure section of the model. This file can be saved and used in your own research and studies, 

and you can create as many other study files as you need. In the Demo1 file, the individual is 

tracked through all age ranges. Press Run and you will begin this simulation leading to the next 

screen: 
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Figure 5: Model component selection window. Click on exposure to run this portion of the 

model. Select all three to run the full model. 

To run the full model, click the small boxes next to Exposure and Absorption (the Biokinetics 

box will automatically insert a √). Press Continue to get the next screen. 

Figure 6: Model status window. Select options to use historical data. 

Click Start, and the model will run for a few seconds. Then you will get two output files which 

can be viewed (Figure 7); these will be saved as a part of this study. 

Figure 7: Retrieve model output file. The *.mod file has day by day record of values for 

the list of selected output options. This list may take a few seconds to pop up on 

the screen, as it may contain over 32000 records, depending on your choice of age 

ranges. 
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Press Continue to save these files using the same filename and to pass onto the next screen. In a 

few seconds, you will get a screen that looks like this: 

Figure 8: Output data file in spreadsheet format. All output parameters may be selected, 

and the file may be exported as a Lotus 123 file or Microsoft Excel file. 

This table shows the output for the model run, giving the lead concentrations (μg/g) in each of 

six compartments every one hundred days for the lifetime of the modeled individual. You can 

plot these now if you wish. 

At this point you should understand that the main purpose of the model is to estimate the 

concentration of lead in selected body tissues based on the exposure of the modeled individual 

over the desired age range (the model runs from birth to the highest selected age range). You 

will see later how you can use the plotting capabilities of the model to view the data in graphic 

form, or export the data to a spreadsheet and develop your own custom made plots and perform 

further statistical analyses to meet your specific data evaluation requirements. 

Now let’s get back to the screen-by-screen description of the model. Returning to the Primary 

Window, observe the following options: 
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Figure 9: Primary Window with Male gender, End Date computation, and one day time 

step selected.

You can: 

1) Select Male or Female 

2) Compute with an end date of today 

3) Change the date from the default date, which is your computer’s date 

3) Select a simulation timestep of one day or one hour2

 

4) Run the model through one to nine age ranges3. 

The Calendar date cannot be changed by editing the date in the date window, because the 

program does not read this date back in to the study file. The date can be changed by clicking on 

this window, thereby calling up a calendar which is capable of recording your selected date in 

the study file (Figure 10). Click on the up/down arrow at the right of the year to change the year. 

 Click on the month right or left arrow to change the month, and then click on the day to set the 

day of the month. 

Default options are preselected for all choices on this screen except the Age Range, and you 

need select only the highest Age Range that you want for your simulation. The rest will be 

populated for you. Take time to note that when you select an age range, the model displays the 

ages and the dates automatically. Thus, if you are interested in an exposure during a specific 

time period in this person’s life, you can make an upper age selection that will include this time 

period in the person’s life. You can also manually adjust the number of days in each age range. 

 

2 Our experience to date has not revealed any situations where the assessment would be enhanced by a timestep 

more frequent than one day. 

3 The Prenatal option is not fully implemented but is included for demonstration purposes. (See Section 4)
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Associated with each age range are one or more exposure scenarios that can be manipulated to 

define the daily exposure for one to four physical locations (e.g. Residential, School, 

Occupational, Recreational) during each of the life stages4

. 

When you are through with this exploration phase, exit the simulation and return to the main 

window. If you wish to reset the parameters to their default value you may do so on any of the 

Media Exposure windows. 

Figure 10. Drop-down window for resetting the model date. Clicking on the date window 

will give the calendar window as shown. The years is selected by toggling up or 

down on the small bars to the right of the year. The month is selected by 

clicking on the left or right arrow on the left or right of the top of the screen. 

The day is selected by clicking on the desired date. 

 

4

 The two youngest age groups do not have the Occupational option, and therefore have only three location options. 
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2: BUILDING THE MODEL RUN 

Building the model run consists of five steps: 

1) define the individual 

2) construct a full exposure scenario 

3) modify the uptake and biokinetic parameters, if necessary 

4) run the model to produce and save the output file 

5) patch the output file into an Excel or Lotus spreadsheet from which you can perform 

further graphic and statistical analyses. 

In every case throughout the model, default input values have been inserted when such a value is 

required for continuation. Accepting these values during the initial exploration of the model 

may enhance the learning curve and give you a feel for the range of values that will meet the 

needs of your study. With the default values that are provided, the model should run as installed 

with minimum modeler input. They can easily be changed and reset. 

a. Age Range: Select the maximum age category you would like for this model run. This 

will automatically populate all younger age categories. Note that these age categories 

are for the purpose of creating the exposure scenario based on reasonable activity 

patterns. Later, you will see age-related distributions for absorption and biokinetic 

parameters that are independent of these exposure and activity pattern age groups. 

 

b. Select the output you desire, with respect to the tissue concentrations. This is done by 

clicking on the Tools option on the bar at the top of the screen (Figure 11), then 

selecting “Set Output.” See Figure 12. The Window is shown in Figure 13. Left click 

to place an ‘X’ in any box for which you want output, and remove the “X” from any 

box for which you don’t want output by left clicking on the “X.” Left click on OK 

when you are done selecting the output options. 

For the purposes of graphic presentation, it is best to group your output selections so 

that they are approximately on the same scale and will display over about the same 

range. This can best be accomplished by trial and error. 

c. Although there are several other options that could be brought into play, it might be 

best to run the model in default mode, just to get a feel for the type of output you can 

expect. Click the RUN button at the right of the box. You must save this study to a 

file. Click OK when asked “Save current study changes?” Clicking Cancel will stop 

the RUN mode at this point and wait for your further input. You can enter a new file 

name (the .xal extension will be added automatically) or click on a previous file from 

the list shown (Figure 14). Click SAVE. 
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Figure 11. Bar along top of screen with Tools option. Clicking on Tools, then Set Output, 

will give the drop down window in Figure 13. 

Figure 12. Tool Selection Menu. Click on ‘Set Output’. 

 

Figure 13. Drop down window to select the output parameters to be displayed and for 

which data are needed for export. 

NOTE: The Insert Event option on the Opening window has been temporarily disabled. 
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Figure 14: Primary window with full specifications for model run, ready for entering 

exposure parameters. 

 

 Figure 15. Save Current Study 

2.1. EDITING PARAMETERS 

2.1.1. MEDIA EXPOSURES 

There is considerable flexibility in the AALM to change the assigned values of the media 

exposure parameters. Each exposure category (AIR, DIET, DUST, WATER, PICA, DERMAL) 

has a separate window, and you can reset the values for these six windows. Air, Diet, Dust, and 

Water ingestion values are set to typical U.S. values and are discussed in this section. Pica and 

Dermal exposure values are, by default, set to zero exposure because they apply to special 

situations not fully documented in the literature. Pica and Dermal exposure are available for 

research purposes and are discussed further in Section 4. 
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Set the parameter window to “Media Exposure” and click the EDIT button. There are two 

options in Window 1a: “Exposure Parameters” and “Historical Exposure Settings.” At this time, 

select “Exposure Parameters” to gain access to Window 1a1: Media Exposure (Figure 17). 

[Historical Exposure Settings are under development and may not execute correctly for this 

evaluation]. The Exposure Parameter window has six tabs, one each for Air, Diet, Dust, Water, 

Pica, and Dermal Exposure. In each of these windows, you can set the values for the key 

parameters for each of the age range options that you have selected, shown in Figure 17 as 

Postnatal to Late Retirement. 

2.1.1.1 Air 

The table for air exposure, shown on this figure, has eight rows of exposure data populated with 

two exposure parameters (amount of lead in air (μg Pb/m3 ) and amount of air inhaled (m3/day) 

for each exposure component: outdoor, residential, school, and occupational. In this way, air 

exposure is calculated as the product of the two parameters μg/m3 and m3/day, giving μg/day. 

In the case of air exposure in the three indoor environments, the amount of lead in air is, for 

convenience, expressed as a percentage of the outdoor lead concentration. The default values are 

set to 30% but may exceed 100% if the modeler chooses to do so. 

The exposure module uses a smoothing feature that assigns the value you select to the middle of 

the age range, then interpolates to the adjacent points of the younger and older age ranges when 

assigning values, day by day, to the intervening time steps. 

 

Figure 16. Select Exposure Parameters to review and modify the exposure portion of the 

model. 
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Figure 17: Exposure options group with Air component ready for review and 

modification. 

The default value of outdoor air is 0.1 μg Pb/m3 (Figure 17). Other options depend on the age 

range selected. The Clear button will clear all values in the “Air” window. The Clear All button 

will clear all six exposure categories and should not be used unless you plan to enter new values 

for all six windows. Likewise, the Default button will repopulate this window with the default 

values as shown, and the All to Default will do so for all six windows. The Historical Lead 

Concentration check window will be discussed in Section 4. 

2.1.1.2 Diet 

The data for lead concentrations in food are taken from the Market Basket Food Survey 

conducted by the Food and Drug Administration. In this survey, specific food products in over 

two hundred categories are purchased at supermarkets periodically throughout the United States 

and sent to a central laboratory where they are prepared in a kitchen environment according to 

the manufacturer’s instructions. These are analyzed for many organic and inorganic components 

according to a strict analytical protocol. These data are reported quarterly and are available at 

the Food and Drug Administration website: 

Market Basket Survey: http://vm.cfsan.fda.gov/~lrd/pestadd.html 

Total Diet Study: http://www.cfsan.fda.gov/~comm/tds-hist.html#fca 

For this report, the data have been compiled, with some adjustments, and have been incorporated 

into the AALM for the periods 1982 to the present. Over the years, the categories of food have 

changed according to national food preferences, and the lead concentrations in these foods have 

declined dramatically, for several reasons5

. From the standpoint of lifetime exposures to lead, 

 

5 Food lead concentrations have decline considerably since the period 1982-85 with the removal of cans with 
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this decline has been relatively recent (i.e. since 1985), and the historical food lead exposure of 

an individual born in the 1960s or earlier can be a significant component of the total body burden 

of lead. 

Select the “Diet” tab to move to the Dietary exposure mode as shown on Figure 19. The 

common features (age categories, dates, option buttons) are the same, and the rows of data are 

similar (amounts ingested, lead concentration) as for the air window. The default setting is for a 

Market Basket Survey Diet subdivided into the main items of Fruit, Vegetables, Meat and Fish. 

To access these alternate sources of food exposure, click on the window tab at the lower left 

corner shown in Figure 19 with the “Market Diet” label. Drop this window down to reveal 

options for Home Garden, Recreational Fishing/Hunting and Subsistence Fishing/Hunting. 

Figure 20 shows the selection of the Home Garden option that includes garden fruit and garden 

vegetables, each with a line for intake percent of diet and lead concentration. The intake percent 

has a default of zero, so that no exposure will be added to the total diet until a number is added to 

this row. You can do this one column at a time by entering a number in each cell or, for all age 

groups by entering a value in the window on the lower left. Note that the default lead 

concentrations are the same as for the market fruit above, so that no change will be seen in the 

diet until new lead concentrations for garden fruits are added, based on situational information. 

Figure 18: Options for Dietary exposure.

 

soldered side seams. Air lead concentrations have also decreased, reducing the amount of lead in food crops. 
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Figure 19. Dietary exposure with garden fruits and vegetables. 

The exposure information for garden fruits and vegetables may be entered in a similar manner, 

again with no change in the exposure unless values on the table are different from their default 

values. 

Other options include modifications if: 1) produce is home grown, or 2) recreational 

fishing/hunting, or 3) subsistence fishing/hunting are significant contributors to the diet. The 

Recreational Fishing and Hunting option provides the opportunity to account for lead exposure 

from the occasional ingestion of foods in the fish and meat category. Enter the data for 

recreational hunting/fishing category through the same process as for home gardening, and select 

garden fruit and vegetable options as well, if they apply. 

The third option is Subsistence Hunting and Fishing, and in this case the intent is to replace all 

market basket meats and fish with meat and fish from non-market sources. This option may also 

be used in conjunction with the home gardening option, in which case the assumption is that all 

food comes from non-market sources. 

Finally, it is important to note that alternate food sources may not necessarily be lower in lead 

content than market food. Historically, the main source of lead in market food was lead from 

cans with a lead-based seal on the side seam. These were removed from the commercial food 

production process during the period 1982-1985, resulting in a dramatic decline in the lead 

concentration of canned food. Likewise, the decline in air lead concentrations during the 1980s, 

with the banning of tetraethyl lead from gasoline, also resulted in a substantial reduction of lead 

in crops. 
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2.1.1.3 Dust 

Household dust (Figure 20) is assumed to be a mixture of deposited particles of atmospheric 

origin, tracked-in soil, deteriorating paint, dust from local commercial industries, and on 

occasion, certain dust generating activities related to the home environment. There are several 

options available with this exposure group. The first decision is to determine the manner in 

which the dust sample was taken: a wet wipe sample gives μg Pb per area sampled (μgPb/cm2 ); 

a dry vacuum sample can give μg Pb per area sampled or per gram of dust collected. If the total 

mass of dust sampled is available, then this can be related to an ingestion rate of dust mass/day, 

usually about 100 mg dust/day. If the mass of dust is not known and only the area sampled is 

known, then the modeler must base the exposure estimate on the hand-to-surface area contact 

and the hand-to-mouth activity of the individual. Furthermore, the efficiency of transfer at the 

time of surface contact, which depends largely on the dampness of the hand, should also be 

estimated. 

Figure 20: Exposure options for dust exposure.

The choice between the concentration method (Conc) (Figure 21) or the area method (Area) 

(Figure 22) can be made by dropping down the window in the lower part of the dust screen. 

The default option for Residential Dust using concentration measurements is shown below. 

The second dust decision is to determine the important sources of dust other than the home that 

might be associated with school, occupational or recreational activities. If this information is 

known or can be determined, these options can be implemented by dropping the window in the 

lower left part of the dust screen, the same window as the choice of [Conc] vs. [Area]. The 

alternate locations are the same options as for air, and are zeroed out until specific information is 

entered by the modeler. 

In determining how to distribute the dust exposure over several alternate sources, the modeler 

must make an estimate of the percent of total dust ingestion that occurs at each location, and the 
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Figure 21: Drop Down window for the Dust component of Media Exposure with the 

options for Other Dust Sources (as Concentration) shown in the lower left dropdown window.

Figure 22: Window for the Dust component of Media Exposure with the options for 

Residential Dust sources (Area) shown in the sub-window at the lower left. 

concentration of lead in that dust. The contribution of lead from dust sources other than the 

home environment will remain at zero until the modeler makes the appropriate alternate dust 

source entries. Another option using the lead loading approach allows for exposure from school, 

occupational and recreational activities (Figure 22 and Figure 23). 
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Figure 23: Window for the dust component of Media Exposure with the options for several 

Dust Sources (as Area and Loading) shown in the sub-window at lower left. 

2.1.1.4 Drinking Water 

As with the previous routes of exposure, conservative estimates of drinking water consumption 

are set at default values of one liter of fully flushed drinking water per day (Figure 24). This 

would include tap water used to prepare coffee or tea, and to reconstitute beverages such as 

frozen juices. It would not include canned or bottled soft drinks, which are treated as food items. 

On this basis, it is likely that the mean consumption of drinking water is higher than one liter, 

possibly 5-6 liters, but this varies by age, climate, season and several other factors, so that a 

conservative estimate seems appropriate as a baseline starting point. Lead exposure from 

drinking water is calculated as μg Pb/L x L/day = μg Pb/day. 

Other options allow for inputs from first draw water, fountain water and bottled water. These 

options may be accessed through the drop-down window at the lower left, by clicking the option 

“Other Water Sources” (Figure 25). This will add options for First Draw Tap Water, Drinking 

Fountain Tap Water, and Bottled Water. Unlike previous exposure sources, the Drinking Water 

options are fully implemented when the “Other Water Sources” button is selected. To change 

the default values, note that each source has a percent-of-total-volume option and this percent 

may be changed for each source and age group. Remember that bottled water and perhaps 

drinking fountains were not readily available in the early 1900s; likewise, there is little reliable 

site specific information on historical drinking water lead concentrations. 
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Figure 24: Window for the Water component of Media Exposure with the default option of 

fully Flushed Water in the sub-window at the lower left. 

Figure 25: Window for the Water component of Media Exposure with the options for 

Other Water Sources shown in the sub-window at lower left. 

[Pica and Dermal Exposure Factors Are Discussed in Chapter 3] 
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2.2 EDITING EXPOSURE ACTIVITY PATTERNS 

Activity patterns determine the amount of time (hours) the modeled individual spends at each 

activity. There are 168 hours in a week. For each age group, these hours are distributed, as 

applicable, among four exposure locations (residential, school, occupational, and recreational) 

using the 168 hours, minus the designated sleep hours per day. Within each location, the 

modeler may designate a percentage of the time spent indoors, allowing for separate estimates of 

indoor/outdoor air and dust lead exposures. 

Three factors determine exposure: 1) the amount of time spent at a particular activity; 2) the 

amount of “media” ingested during that time; and 3) the concentration of lead in that media. For 

food and drinking water lead concentrations, the location may not be a factor if supermarket food 

and municipal water are consumed, as these are usually monitored closely and tend to be the 

same throughout the United States. Air and dust lead concentrations are likely to be different by 

location and are treated as such in this model. 

During the postnatal period, which lasts six months, the child is presumed to be in a highly 

protective environment with limited access to dust collecting surfaces and under continuous 

observation by a caregiver. Consequently, only one exposure environment, “Residential” is 

provided in the model. In the event there needs to be a second environment, this can be 

accomplished by reducing the time frame for Postnatal status and expanding the Toddler time 

frame. 

Figure 26: Drop down window for the Activity Patterns component of Media Exposure 

showing default values for activity patterns for Postnatal. 

2.3 Summary and Conclusions 

This concludes the introduction to the General Guidance for Media Exposure. Most risk 

assessment problems for lead exposure can be handled with the development of an exposure 

scenario involving the model features discussed in this section followed by a statistical 
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extrapolation of the predicted blood lead concentration for an individual to a mean blood lead 

concentration for a population of similarly exposed individuals. 

At this point, you may find it helpful to enter your own exposure settings and save the file as a 

useful starting point for further research or investigation. Section 4 provides guidance on special 

features and work-arounds for special problems and situations. If these features do not apply to 

your needs, you may proceed directly to Section 5 and begin adjusting the model for lead 

absorption. 

When you have completed constructing the exposure scenario for your subject, it is wise to give 

it a brief reality check. To determine whether you have correctly modeled the exposure of the 

individual, imagine yourself in that person’s place for one week and determine whether or not 

you would have captured all or most of your exposure for that time. Remember that, in some 

cases, you may account for exposure at two locations as they were one. That is, your exposure at 

the office may be, for all practical purposes, the same as at the library or at a concert hall, and 

could be treated as one location. 

Figure 27: Following set of the Exposure Scenario, the model run is initiated by checking 

the Exposure and Absorption boxes. The Biokinetics box will be automatically 

checked. 

At this point you may choose to run just the exposure portion of the model by selecting that box 

in the Model Run Window (Figure 27). In this case, you will get two files, *.mod and *.mpa 

(Figure 28). The first (*.mod) is a complete list, day by day, of exposure and may contain up to 

32841 lines of data for the six exposure categories (air, diet, water, dust, dermal and pica). 

The second file (*.mpa) contains a summary of these six exposure categories for each age 

category selected. You will also have an opportunity to view these files after the 

absorption/biokinetics portion of the model has been executed. 
9/27/2005 DRAFT: DO NOT QUOTE OR CITE 30

 

 Figure 28. Two files are available for review, *.mod and *.mpa. 

 Figure 29. Line by line output for the exposure module. *.mod 

 Figure 30. Total exposure by age for each exposure category (*.mpa) 
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Figure 31: Exposure Model options with options to change internal exposure and growth 

parameters. 
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SECTION 3: SPECIAL EXPOSURE FEATURES

There are three model features that have been incorporated into the Exposure component of the 

All Ages Lead Model that reflect special cases with respect to human exposure to lead. These 

are pica ingestion, dermal absorption, and maternal (or prenatal) exposure. The AALM permits 

the modeler to explore these routes of exposure with the caveat that these features are under 

development and have not been fully tested. Furthermore, there is little scientific information 

available to document the basis for parameter inputs and very little guidance can be given. 

3.1 PICA EXPOSURE 

This document defines pica as the habitual tendency or craving to ingest non-food items such as 

paint chips and soil. In the default mode, numeric values for the amount of ingested soil and 

paint chips are set at 0, so that no contribution from pica will be included in a study without the 

intentional specification of some positive value for this ingestion rate. To activate the pica 

mode, simply enter an estimate the amount of soil or paint chips that might be ingested during 

any of the life stages of the individual, and revise, if necessary, the lead concentration in that soil 

or dust (Figure 32). Experience will soon show that pica can, at reasonable ingestion rates, 

dominate the exposure of the individual. 

 

Figure 32: Window for the Pica component of Media Exposure. 

3.2 DERMAL EXPOSURE

The frequency of lead exposure via the dermal route remains poorly defined in the literature, 

especially the mechanism by which it is absorbed into the body. Nevertheless, dermal absorption 

can be an important contributor to children playing in dusty situations, such as sand boxes. It 

may also occur with occupationally-exposed subjects working with fine dusts and under hot, 
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sweaty conditions. The default values for dermal absorption parameters are arbitrary and not 

based on specific scientific studies. Like pica, dermal exposure is set to zero by default values 

for soil and paint chip ingestion (Figure 33) and may be activated by changing these values to 

some positive number. 

Figure 33: Window for the Dermal component of Media Exposure. 

3.3 HISTORICAL LEAD EXPOSURES 

In the case where the exposure scenario extends back in time to the early 1900s, the model 

default values for some parameters may not be accurate in light of high exposures, due to the use 

of food cans with lead soldered side seams and gasoline with tetraethyl lead. This feature, still 

under development, will allow the modeler to insert historical food data from 1982 to the present 

and actual air lead measurements from the early 1970s. This information will also provide 

guidance for reasonable estimates of exposure to these media for the years prior to the time 

accurate date were available. 

3.4 MATERNAL EXPOSURE (Conceptual Design) 

Maternal exposure results from the transfer of lead from the mother to the developing fetus 

during the nine months of fetal development. The model treats this exposure as a single source 

(the mother’s blood) that determines the tissue concentrations of the infant at the time of birth. 

Thus, with this component activated, exposure begins at the formation of the embryo. Until 

birth, this developing fetus is modeled as a separate compartment of the mother’s model. At the 

time of birth, a new file is created, representing the child’s accumulated exposure with tissue and 

organ concentrations derived from maternal exposure rather than the default for the postnatal 

infant model. 
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SECTION 4: ABSORPTION MODULE 

4.1 MODELING LEAD ABSORPTION 

Similar to the Exposure Module, the Absorption Module has a set of parameters that represent 

specific body functions related to lead absorption, and these parameters can be adjusted to reflect 

the absorption of lead from the lungs and the digestive tract. A third absorption option would be 

dermal absorption when it is fully implemented. As with the Exposure module, all parameters in 

the Absorption module can be changed by replacing the default values with “exploratory” values 

that the modeler may find applicable to a specific situation. Two groups of parameters can be 

edited in this module, lung absorption and digestive tract absorption. 

Lung absorption is derived from the Leggett model, where there are four lung compartments, 

each with two absorption parameters (Figure 34). The first parameter (Fraction) is the fraction 

of the total amount of lung lead that is deposited in the lung, and the second parameter is the 

amount per day that is transferred to the blood compartment. 

 

For ingested food, the rate of movement through the gastrointestinal tract varies by more than 

just the age of the individual. No distinction is made in the model among the three sections of 

the small intestine (duodenum, jejunum, ileum) or their function. The gastro-intestinal 

absorption of lead in children and adults has been thoroughly described (Mushak, 1991). Issues 

that are of special interest for modeling purposes include the physical process of preparing the 

food for nutrient absorption, as well as the physiological and biochemical process of absorption. 

 Following digestion in the stomach, absorption occurs across the epithelial lining of the 

intestinal mucosa, the additional folds of the submucosa, and the microscopic folds of the villi 

and microvilli. This gives the total absorbing surface not only a large physical area across which 

nutrients can pass, but a highly complex microenvironment whereby non-nutrients such as lead 

can pass into the blood stream with a high degree of localized variability. 

The rate of movement through the gastrointestinal tract is the reciprocal of the number of days 

the lead would reside in the G.I. tract (Leggett, 1993). During this time, several digestive and 

absorption mechanisms break down the food ingested into simpler chemical and biochemical 

components that can be transported across the wall of the small intestine. Among these are a 

group of nutrient elements, including calcium, iron, and phosphorus, that are chemically similar 

to lead. Lead is postulated to follow these essential nutrients by a combination of three 

mechanisms: diffusion, pinocytosis, and facilitated transport (Leggett, 1993). 

Stable isotope studies have shown, at least for adults, that fasting can greatly increase the rate of 

absorption (Maddeloni et al, 1998). Whereas the mechanism is not fully understood, it is highly 

likely that calcium plays a significant role is preventing the uptake of lead. Theoretically, if there 

is sufficient calcium in the digestive tract, lead will be excluded to some degree. But, at a microsite of absorption that is partially isolated by the intricate folds of the submucossa, the calcium 

may be absorbed during fasting periods and not replenished, leaving the lead available at higher 

relative concentrations. Without modeling calcium ingestion and absorption at the same time as 

lead ingestion and absorption, it is difficult to correctly estimate the true rate of lead absorption. 
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Figure 34. Schematic diagram of the Leggett Model. This model shows the routes of 

absorption as the Respiratory Tract (RT Tract) and Gastrointestinal Tract (GI 

Tract) contributing lead to the Diffusible Plasma compartment. A further 

discussion of this model may be found in Chapter 5. 

Recent data from stable isotopic studies suggest that the GI absorption fraction in children is 

similar to adults (Gulson, 2005). 

It is clear that much remains to be discovered with respect to the mechanisms of gastrointestinal 

absorption of lead. With its open architecture and flexible application of input parameters, the 

All Ages Lead Model is designed to facilitate continued research on such critical matters as the 

intake and absorption of lead, and to accommodate the results of that research through the 

adjustment of the key absorption parameters. 

Brain

Liver 2

Liver 1

Liver

Diffusible 

Plasma

ExtraVascular

RBC

Tenacious 

Turnover

Rapid 

Turnover

Intermediate 

Turnover

Other Soft Tissues

Cortical 

Surface

Trabecular 

Surface

Cortical Volume

NonExchange Exchange

Trabecular Volume

NonExchange Exchange

Skeleton

RT Tract

GI Tract

Other 

Kidney 

Tissue

Urinary 

Path

Kidneys

Bladder 

Contents

Urine

Feces

Losses in 

Hair, Nails, 

Skin

Sweat

Bound 

Plasma

Brain

Liver 2

Liver 1

Liver

Diffusible 

Plasma

ExtraVascular

RBC

Tenacious 

Turnover

Rapid 

Turnover

Intermediate 

Turnover

Other Soft Tissues

Tenacious 

Turnover

Rapid 

Turnover

Intermediate 

Turnover

Other Soft Tissues

Cortical 

Surface

Trabecular 

Surface

Cortical Volume

NonExchange Exchange

Trabecular Volume

NonExchange Exchange

Skeleton

RT Tract

GI Tract

Other 

Kidney 

Tissue

Urinary 

Path

Kidneys

Other 

Kidney 

Tissue

Urinary 

Path

Kidneys

Bladder 

Contents

Urine

Feces

Losses in 

Hair, Nails, 

Skin

Sweat

Bound 

Plasma
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Figure 35: Drop down window for reviewing and revising Delta step values. These are the 

internal time step functions for Absorption and Biokinetics, and, by default are 

set at 1 day of simulation. They can be varied individually. The model also 

interpolates between these steps using the Linear option. The other options for 

Interpolation Type are Floor, Ceiling, and Index, which have not been 

evaluated for AALM applications, but are included for research purposes. 

Figure 36: Window for editing Absorption Parameters. 

4.2 ABSORPTION OF INHALED LEAD 

This represents the amount of lead transferred from the lungs (through mucociliary lift into the 

stomach) and liver to the gastrointestinal tract where it is eliminated as feces. It does not include 

ingested lead that was not absorbed during digestion. The coefficient for the deposition fraction 

in feces (0.006) is smaller (slower) than urine (0.015) and is also constant for all age groups. 

Gastrointestinal absorption is treated as a simple percent of absorption through the small 
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intestine, with no variation given to the type of food consumed or daily rhythms. This function 

includes lead that has passed from the stomach to the duodenum and lead in bile excreted from 

the liver. 

4.3 ABSORPTION OF INGESTED LEAD

Figure 37: Drop down window for gastrointestinal absorption showing default values as a 

decimal percentage by age range (in years). The age breakpoints are not the 

same as the breakpoints for exposure that are assigned on the Opening Menu. 

The absorption values may be reset within the range of 0.0-1.0. Data are 

plotted on Figure 38. 

Figure 38 

Figure 38: Plot of the default values for the gastrointestinal absorption fraction. Note that 

the GI absorption fraction for the first three months, when the diet is largely 

liquid, is much higher than at age one year and higher. 
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Figure 39: Default values for the gastrointestinal rate of movement function. Units are 

fraction of whole mass per day (e.g. from age 0-1, the child passes food at the 

rate of 1.6 volumes per day). Data are plotted on Figure 40. 

 

Figure 40: Plot of the default values for the rate of gastrointestinal movement function. 

This function, in default form, reaches maturity at age 15 years and remains 

constant thereafter. 
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SECTION 5: BIOKINETICS MODULE 

There are three groups of parameters in this module for which parameters may be edited. These 

are: Model Settings, Biokinetic Parameters, and Body Size. As with some absorption parameters 

in the previous section, there are several biokinetic parameters that may be adjusted according to 

age, thus giving considerable flexibility in the application of the model to a wide range of 

populations. 

5.1 MODEL SETTINGS 

This set of seventeen functions (Figure 42), shown also in Table 1) has three types of 

parameters: that are assigned default values, at the initialization of the model. Some of these are 

simply on/off switches that turn on or off an optional model feature selected by the modeler for a 

particular function. Other parameters for which default values have been assigned can be 

changed by the modeler. Two parameters, Delta Step Lengths and Bone Computation, have drop 

down windows that allow the modeler to select a specific value or option. The Delta step lengths 

are the ‘inflection’ points along the age range, and are not necessarily the same points as for age 

categories for the earlier exposure model component. This option allows for changes, for 

example, in cortical bone turnover to be specified for times different from the age categories 

related to growth and exposure. 

 

5.1.1 PARAMETERS WITH EXPLICIT VALUES 

These eight parameters have only one variable each (i.e., they are not age-dependent). This 

default value can be modified by the modeler. For example, the Exposure age (age at the 

beginning of exposure), which has a default of one day (0.00274 years) can be changed to 1, 

which would start the exposure at age one year. 

The Last Day has a maximum value of 32850 (days), as does the Maximum Cycles. If either of 

these is changed, the lower value would prevail. 

The Output Step Interval simplifies the output by tallying the results over each 100 day segment, 

and this interval can be changes as well. 

The RBC (Red Blood Cell) Threshold Concentration has a default value of 60 μg/dL, below 

which lead is taken up by red blood cells linearly; above that concentration, the uptake process is 

non-linear. One of the parameters of this nonlinearity (Parameter 2) has a value of 350, and a 

part of the equation is expressed to the power of 1.5. The Fixed Delta has a default value of 1.0 

days, which may be changed by the modeler. 

Of the seven On/Off switches, five simply turn a specific function on or off (Fetal Exposuredefault off; Fixed Length Delta option – default variable i.e. off; Acute/Chronic – default chronic 
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exposure; Linear/Non Linear Model – default Linear; Chelation – default off; Body Size Curve – 

default off)6

 

One switch has four possible values: Mode of Intake: 0= injection, 1=inhalation, 2=ingestion, 

3=combination; the default is combination and the model has not been tested for any other mode. 

PARAMETER 

DEFAULT

VALUE TYPE 

Exposure age 0.002740 Function with default value 

Last Day 32850 Function with default value 

Maximum Cycles 32850 Function with default value 

Fetal Exposure 0 On/Off Switch 

Fixed Length Delta Option 0 On/Off Switch 

Delta Step Lengths EDIT Drop down window with age-related 

variables 

Output Step Interval 100 Function with default value 

Acute/Chronic 2 On/Off Switch 

Mode of Intake 3 On/Off Switch 

Linear/Nonlinear 1 On/Off Switch 

RBC Threshold Concentration 60 Function with default value 

Nonlinear Parameter 2 350 Function with default value 

Power 1.5 Function with default value 

Chelation 0 On/Off Switch 

Fixed Delta 1.0 Function with default value 

Body Size Curve 0 On/Off Switch 

Bone Computation Use Leggett Drop down window to select the Leggett or 

O’Flaherty method of bone lead kinetics 

Table 1. Biokinetic model settings showing the three types of editable variables (Function 

with default value, On/Off Switch, or Drop Down window) common to several 

model options. 

The second drop down window allows the modeler to select the bone methodology of either 

Leggett or O’Flaherty. The Leggett method is generally considered to be anatomically based 

and offers the modeler several options within the complex of bone compartments. The 

O’Flaherty method is physiologically based and promotes the concept of lead following the 

physiological pathway of calcium in bone tissue (O’Flaherty et al, 1998). This feature is a 

relatively new addition to the model and has not been fully implemented. The schematic 

diagram for the O’Flaherty model appears in Figure 41. 

 

6 Note that one of the earlier uses of the Leggett model involved the removal of lead from blood by chelation. This 

feature is rarely used, but was retained against the possibility of some future use. 
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Figure 42: Window for editing the model settings. Features other than the Delta Step 

Length have options than do not vary with age.

R e s p ira to ry tra c t

B lo o d p la s m a

W e ll-p e rfu s e d tis s u e s

P o o rly -p e rfu s e d tis s u e s

C o rtic a l b o n e

T ra b e c u la r b o n e

L iv e r

K id n e y

U rin e

A ir

D ie t, D u s t, 

P a in t, S o il, 

W a te r

Feces

G a s tro in te s tin a l tra c t

E lim in a tio n p o o ls o f

th e b o d y

In ta k e fro m e n v iro n m e n ta l

M e d ia (μ g /le a d /y e a r)

B o d y c o m p a rtm e n t

Figure 41. Schematic Diagram of O'Flaherty Model. This model addresses the 

physiological process of lead movement in bone tissue and is currently being 

tested for compatibility with the All Ages Lead Model
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Figure 43: Drop down window for editing the default Delta Step lengths.

5.2 BIOKINETIC PARAMETERS 

The second option in the Biokinetic Parameter Window is the option to “Edit Biokinetic 

Parameters,” a window that lists 47 parameters, all of which have numeric values or age-related 

sets of numeric values. Most of these are directly or indirectly related to the arrows connecting 

the various compartments of the schematic model, Figure 45 (Pounds, J.G.; Leggett, R.W. 

(1998). 

Figure 44: Window for editing biokinetic parameters. The bottom half of this window 

includes parameters 24 through 47 and appears in Figure 78.
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5.2.1 Pb DECAY RATE. 

This rate of decay for lead has a default of 0 and should be left at this value as it is not currently 

used. It is reserved for future use. 

Figure 45. Schematic Diagram of Leggett Model. The small numbers correspond to the 

numbered parameters in Figure 44 and Figure 78. The central exchange 

compartment is diffusible plasma. Bone is represented as having surface (which 

exchanges with plasma) and volume compartments; the latter simulates slow 

exchange with the surface and slow return of lead to the plasma from bone 

resorption. Pounds, J.G.; Leggett, R.W. (1998). 

5.2.2 CORTICAL BONE TURNOVER. 

This is one of three parameters that regulate the transfer into and within the cortical bone tissue 

(Figure 44). The value for the turnover rate is age-dependent and decays to a value nearly zero 

by age fifteen (See Figure 46). This allows changes in the rate of cortical bone turnover to be 

made for the Age Ranges (Delta Steps) that are specified in Biokinetics Model Settings, line 6. 

Units 

40 

36

26 

13 

18

34 

14

3

2

39

35 41

8

38

20

31 17 16 32 15 33

22 

10 

21 

12 

9

9

5

4

8

7

6

30

11

Brain

Liver 2

Liver 1

Liver

Diffusible 

Plasma

ExtraVascular

RBC

Tenacious 

Turnover

Rapid 

Turnover

Intermediate 

Turnover

Other Soft Tissues

Cortical 

Surface

Trabecular 

Surface

Cortical Volume

NonExchange Exchange

Trabecular Volume

NonExchange Exchange

Skeleton

RT Tract

GI Tract

Other 

Kidney 

Tissue

Urinary 

Path

Kidneys

Bladder 

Contents

Urine

Feces

Losses in 

Hair, Nails, 

Skin

Sweat

Bound 

Plasma

Brain

Liver 2

Liver 1

Liver

Diffusible 

Plasma

ExtraVascular

RBC

Tenacious 

Turnover

Rapid 

Turnover

Intermediate 

Turnover

Other Soft Tissues

Tenacious 

Turnover

Rapid 

Turnover

Intermediate 

Turnover

Other Soft Tissues

Cortical 

Surface

Trabecular 

Surface

Cortical Volume

NonExchange Exchange

Trabecular Volume

NonExchange Exchange

Skeleton

RT Tract

GI Tract

Other 

Kidney 

Tissue

Urinary 

Path

Kidneys

Other 

Kidney 

Tissue

Urinary 

Path

Kidneys

Bladder 

Contents

Urine

Feces

Losses in 

Hair, Nails, 

Skin

Sweat

Bound 

Plasma
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Figure 46: Values for cortical bone turnover rate which decreases with age. Data are 

plotted on Figure 47. 

Figure 47: Plot of default values for cortical bone turnover rate by age. This Y-axis scale 

appears to show values less than zero, but this is a rounding error. Above the 

age 25 years, this value is 0.000082

are percent fraction per day. The values decrease exponentially from age 0 to 25 years, from 

0.01% at birth to 0.00008% at age 25 and older. Interpolation between age groups may be 

specified as linear, floor, ceiling, or index. During early development, cortical and trabecular 

bone turnover are modeled at nearly the same rate; by age 25, cortical turnover is about 17% of 

trabecular. 

5.2.3. TRABECULAR BONE TURNOVER RATE. 

At one year and younger, the turnover for trabecular bone is modeled at the same rate as cortical 

(See Figure 48 et seq.). Above one year, the trabecular bone turnover rate decreases slightly less 

than cortical. Changes to trabecular bone turnover rates can be made for the same Age Ranges or 

independently of the changes for cortical bone turnover rates. 
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Figure 48. Age specific values for Surface to Volume in Trabecular Bone. Data are plotted 

on Figure 49. 

Figure 49. Plot of Trabecular Surface to Volume.

Figure 50: Values for trabecular bone turnover rate by age. Data are plotted on Figure 51. 

Figure 

51
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Figure 51: Plot of default values for trabecular bone turnover rate by age. 

5.2.3 TRANSFER FROM CORTICAL SURFACE TO BLOOD PLASMA. 

The model treats the bone surface as the major route of transfer from cortical bone surface to 

both blood plasma and bone volume. In the case of adults, the transfer from the cortical bone 

surface is split evenly between transfer to blood plasma (Figure 52) and bone volume (Figure 

56), thus the coefficient for ages over 15 is 0.5/day. For the younger age groups, this distribution 

differs between the two: 0.65/day to blood plasma and 0.35/day to cortical bone volume. 

Figure 52: Dropdown window for editing the parameter for transfer from cortical surface 

to blood. Data are plotted on Figure 53. 
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Figure 53: Plot of the default values for the parameter for transfer from cortical surface to 

blood. 

5.2.4. TRANSFER FROM TRABECULAR SURFACE TO BLOOD PLASMA. 

Trabecular surface to blood plasma transfer rates are modeled the same as cortical surface to 

plasma. For the younger age groups, this distribution is 0.65/day to blood plasma (Figure 54) and 

0.35/day to trabecular bone volume (Figure 58). For ages over 15 is 0.5/day for each route. 

 

Figure 54: Drop down window for editing the parameter for the transfer rate for 

trabecular surface to blood. Data are plotted on Figure 55.
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Figure 55: Plot of the default values for the transfer rate for trabecular surface to blood.

5.2.6 CORTICAL SURFACE TO VOLUME TRANSFER. 

This is the fraction per day that is transferred from the cortical bone surface to the volume of the 

cortical bone and is equal to [1-(transfer to blood)]. The default values are 0.35 for the younger 

ages (0-15 years), then 0.5 for the older ages. 

Figure 56. Window for editing the value for transfer from cortical surface to volume. Data 

are plotted on Figure 57. 
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Figure 57: Plot of the default values for transfer from cortical surface to volume. 

5.2.7 TRABECULAR SURFACE TO TRABECULAR VOLUME TRANSFER. 

Similar to the cortical surface to volume transfer, this parameter accounts for the fraction of 

trabecular surface lead that is transferred trabecular volume. The age-dependent default values 

are the same as the cortical counterpart, 0.35 for children and 0.5 for older children and adults. 

Figure 58: Window for editing the values for transfer from trabecular surface to volume. 

Data are plotted on Figure 59.
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Figure 59: Plot of the default values for transfer from trabecular surface to volume.

5.2.8 TOTAL TRANSFER FROM EXCHANGE BONE VOLUME. 

Based on radium data, the removal halftime of lead from the exchangeable bone volume is 

30 days, during which time 20% of the lead passes to the non-exchangeable bone tissue and 80% 

returns to the bone surface, and is the same for cortical and trabecular bone. Although this is an 

age-dependent variable, the current default value is the same for all age groups (Figure 60). 

Figure 60: Window for editing values for total transfer from the exchange bone volume. 

The plot feature has been temporarily disabled. 

5.2.9. TRANSFER FROM THE EXCHANGE TO THE NON-EXCHANGE VOLUME. 

This parameter combines the cortical and trabecular bone lead transfer from the exchange 

volume to the non-exchange volume compartments and has the same default value (0.2) for all 

age ranges (Figure 61). 
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Figure 61: Window for editing values for total transfer from the non-exchange bone 

volume. The plot feature has been temporarily disabled. 

5.2.10. TRANSFER FROM LIVER1. 

This is the fraction per day that is transferred from Liver1 to the three compartments: 

Gastrointestinal tract, Diffusible Plasma and Liver 2. The default value of 0.0693 is constant for 

all age ranges. The liver and kidney compartments are excretion pathways. The liver may 

contain 2-3% of the total body burden of lead, and this is treated as residing in two 

compartments, Liver1 and Liver2. From Liver1, lead may pass to the small intestine, back to the 

Diffusible Plasma, or to the Liver2 compartment (Figure 45). 

5.2.11 TRANSFER FROM KIDNEY1. 

Transfer from the kidney has two components: Kidney 1 from the kidney back to diffusible 

plasma and Kidney 2 to Kidney 1 from the bladder. Kidney 2 is discussed in Section 5.2.14. 

The fraction that is transferred from Kidney 1 has a transfer rate constant (0.139/day) for all 

ages. 

5.2.12 TRANSFER FROM BLADDER TO URINE. 

Lead that enters the bladder passes from the diffusible plasma to the urinary bladder and from 

the renal tubules. Estimates of urinary excretion removal halftime in humans in vivo are about 

0.1 day (Leggett, 1993). The model includes two routes: Diffusible Plasma to the Urinary Path 

and Diffusible Plasma to Other Kidney Tissue. From the Bladder to Urine is, for all practical 

purposes, instantaneous. 
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Figure 62: Window for editing the values for the transfer of lead from the bladder to 

urine. Data are plotted on Figure 63. 

Figure 63: Plot of the default values for the transfer of lead from the bladder to urine. 

This age-dependent variable excretes lead in urine away from the bladder. The 

values are units per day and are larger for younger children. They become 

constant at about age fifteen. 

5.2.13 TRANSFER FROM LIVER2. 

Of the lead leaving the Liver1 compartment, ten percent is assigned to a long term storage 

compartment, Liver2. The rest is split between the small intestine and diffusible plasma (45% 

each). This age-dependent variable becomes constant at about age 10 years. The transfer rate is 

calculated as 0.1 x 0.0693/day, for a value of 0.00693 in the younger age groups (Figure 64). 
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Figure 64. Age-related coefficients for transfer of lead from Liver2. Data are plotted on 

Figure 65.

Figure 65. Plot of the transfer of lead from the liver 2 compartment. 

5.2.14 TRANSFER FROM KIDNEY2. 

This transfer for Kidney 2 represents the amount of lead that passes to the Bladder from the 

kidney. The numeric values are the same as for Liver 2, and they are age specific (Figure 66). 
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Figure 66: Drop down window for editing the default values for the transfer of lead from 

the kidney. Data are plotted on Figure 67. 

Figure 67: Plot of the default values for the transfer of lead from Kidney 2 (From Kidney 

to Bladder).

5.2.15 TRANSFER FROM FAST SOFT TISSUE. 

Soft tissue consists of muscle, fat, and skin. Although this compartment represents a large 

fraction of the total body mass, the concentration of lead is low. This parameter is substantially 

larger than other values and is age-related (Figure 68). All of the soft tissue is in one 

compartment, but the binding capacity within that compartment is not uniform throughout. The 

model treats the binding capacity as three strengths, although in reality there may be a continuum 

from low to high. The three strengths are Tenacious Turnover, Intermediate Turnover, and 

Rapid Turnover. These three turnover rates, with one exception, return the lead to the Diffusible 

Plasma. The exception is hair, nails and skin, which are described below. 
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Figure 68: Drop down window for editing the default values for the deposition fraction of 

lead in fast soft tissue. Data are plotted on Figure 69.

Figure 69: Plot of the default values for the deposition fraction of lead in fast soft tissue.

5.2.16 TRANSFER FROM INTERMEDIATE SOFT TISSUE. 

This parameter is not age-related and is nearly three orders of magnitude lower than Fast Soft 

Tissue. Some of this lead is “excreted” in the form of hair, nails, and skin. Note the relative 

significance of the pathways for the deposition fraction of lead from the body: feces (0.006) 

urine (0.015, hair/skin/nails (0.4) and sweat (0.0035). The Intermediate Soft tissue excretion 

fraction (0.4) represents a major excretion route (Hair, Nails, and Skin), two orders of magnitude 

larger than sweat. This parameter is also not age-dependent. 
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Figure 70: Drop down window for editing the default values for the deposition fraction of 

lead in intermediate soft tissue. Data are plotted on Figure 71.

Figure 71: Plot of the default values for the deposition fraction of lead in fast soft tissue.

5.2.17 TRANSFER FROM SLOW SOFT TISSUE. 

This parameter is not age-related and is among the slowest, being more than an order of 

magnitude slower than Intermediate Soft Tissue. 
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Figure 72: Drop down window for editing the default values for the deposition fraction of 

lead in slow soft tissue. Data are plotted on Figure 73.

Figure 73: Plot of the default values for the deposition fraction of lead in slow soft tissue.

5.2.18 TRANSFER RATES FROM BRAIN. 

The default value for this age-dependent parameter is very small (0.00095/day) and is modeled 

the same for all age categories. The brain is especially vulnerable to lead, possible due to the role 

calcium plays in nerve conduction velocity. Although it contains very little lead, brain tissue is 

an important component of this biokinetic model. The small amount of lead taken up by the 

brain is strongly retained. The assumed deposition fraction for infants (0.00045) is arbitrarily 

three times higher than for older children and adults (0.00015), which is based on a removal halftime of two years (Figure 74) (Leggett, 1993). 
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Figure 74: Drop down window for editing the default values for the deposition fraction of 

lead in the brain. Data are plotted on Figure 75. 

Figure 75: Plot of the default values for the deposition fraction of lead in the brain. The 

scale on the X-axis have been increased by 103

 for presentation purposes to 

avoid the appearance of a rounding error.

5.2.19 DEPOSITION FRACTION IN URINE. 

More than twice the size of the Feces compartment, this fraction is a major elimination route for 

lead. The coefficient is 0.015 and is constant for all age groups. This number represents the 

transfer rate from the diffusible plasma to the urinary bladder. The Deposition Fraction for lead 

in Feces is 0.006, less than half that of Urine, and represents the lead entering the digestive tract 

from the mucociliary lift mechanism in the Lungs and the passage of lead in bile from the liver. 

The Sweat deposition fraction 0.0035 represents the small amount of the lead that is eliminated 

by the sweat pathway, and is not age-dependent. The value is somewhat arbitrary (0.0035) in 

that it is assumed that 0.35% of the lead leaving the diffusible plasma does so by the sweat route. 
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5.2.20 DEPOSITION FRACTION IN BONE. 

This age-dependent variable represents deposition to bone surfaces and varies widely in children 

 and young adults, up to age 25, after which it reaches a low, constant value of 0.08 (unitless), 

about one third that of a newborn child (Figure 76). This means that, for children under 20, the 

history of lead exposure, as released from their bone tissue, can be as important a contributor to 

blood lead as their current exposure. 

Figure 76. Deposition fraction in Bone. Data are plotted on Figure 77. 

Figure 77. Plot of Deposition Fraction in Bone. Given that the deposition of lead appears 

to be similar to the deposition of alkaline earth elements calcium, strontium, 

and barium (Leggett, 1993), it follows that the spike at age 15, which probably 

represents a spurt in bone growth, would occur also for lead. 
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Figure 78. Bottom of biokinetic Parameters Window. Parameter 47 is Chelation Factor 3 

and has a value of 1250. 

5.2.21 TRABECULAR BONE DEPOSITION FRACTION. 

The fraction of deposition going to trabecular bone ranges from 0.20 to 0.56 (Figure 79), 

increasing with age. As the bone grows, lead is incorporated into the crystalline structure of the 

bone tissue and replaces calcium. Later, as new bone tissue replaces old, the lead is released 

from the nonexchangeable trabecular volume and passes back to the Diffusible Plasma. 

Figure 79. Age-dependent variable for Trabecular Bone Deposition Fraction. Data are 

plotted on Figure 80. 
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Figure 80. Trabecular bone deposition fraction. 

Figure 81: Plot of the default values for the transfer of lead from the liver. 

5.2.22 DEPOSITION FRACTION IN COMPARTMENTS WITHOUT AGE 

VARIABILITY. 

This is the fraction of lead (0.04) deposited in Liver1 from Diffusible Plasma, and does not vary 

with age. This Liver 1 Fraction receives 4% of the lead released by Diffusible Plasma, giving a 

transfer rate of 80/day and a removal halftime of ten days. Ten percent (0.1) of the Liver 1 
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fraction moves to the second liver component, Liver 2. Forty-five percent (0.45) of the Liver 1 

fraction is deposited in the Small Intestine through the bile duct. Most of this is eliminated with 

feces; a small amount may be reabsorbed into the Diffusible Plasma. 

All of the lead from Liver 2 is passed back to the Diffusible Plasma compartment. Most of the 

lead in Liver1 passes into the bile duct and then to the small intestine. The rest (0.45) passes 

back to the Diffusible Plasma. The fraction deposited in Kidney 1 from Diffusible Plasma (0.02) 

is also called the Urinary Path (UP). It has a high deposition but a shorter retention than Kidney 

2. The fraction deposited in Kidney 2 from Diffusible Plasma (0.0002) is also called “Other 

Kidney Tissue (OKT). Although it has a lower uptake than Kidney 1, Kidney 2 has a much 

larger retention time. Lead passes out to the Diffusible Plasma compartment from the OKT. 

5.2.23 DEPOSITION FRACTION FROM DIFFUSIBLE PLASMA TO FAST 

SOFT TISSUE. 

This fraction deposited in Fast Soft Tissue from Diffusible Plasma varies slightly with age and 

has a value from 0.08345 to 0.08875 for a transfer rate of 167-177/day. (Transfer Rate = 

Deposition Fraction x 2000/day) (Figure 82). 

Figure 82. Age-dependent variable for Diffusible Plasma to Fast Soft Tissue. Data are 

plotted on Figure 83. 
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Figure 83. Plot of the default values for the Diffusible Plasma to Fast Soft Tissue 

parameter. 

5.2.24 DEPOSITION FRACTION FROM DIFFUSIBLE PLASMA TO INTERMEDIATE 

SOFT TISSUE. 

This is the fraction deposited in Intermediate Soft Tissue from Diffusible Plasma with a turnover 

rate of 25 to 300 days and includes a component of permanent elimination (Hair, Nails, and 

Skin). This compartment has a Deposition Fraction from 0.005, giving a transfer rate of 

0.00277/day to HNS and 0.00416 to Diffusible Plasma (Figure 84). 

Figure 84. Age-dependent variable for Diffusible Plasma to Intermediate Soft Tissue. 

Data are plotted on Figure 85. 
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Figure 85. Plot of the default values for the diffusible Plasma to Intermediate Soft Tissue 

parameter. 

5.2.25 DEPOSITION FRACTION FROM DIFFUSABLE PLASMA TO SLOW 

SOFT TISSUE. 

A small amount of lead is transferred from Diffusible Plasma to Slow Soft Tissue with a turnover 

rate from 1500 to 10000 days in Slow Soft Tissue. The removal half time is 5 years and transfer 

rate 2/day in, and 0.00038/day out of the compartment. 

Figure 86. Age-dependent variable for Diffusible Plasma to Slow Soft Tissue. Data are 

plotted on Figure 87. 
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Figure 87. Plot of the default values for the Slow Soft Tissue Parameter. 

5.2.26 DEPOSITION FRACTION FROM DIFFUSIBLE PLASMA TO BRAIN. 

This is the fraction deposited in Brain from Diffusible Plasma, and is age-dependent. 

Figure 88. Age-dependent variable for the Deposition Fraction from Diffusible Plasma to 

Brain. Data are plotted on Figure 89. 
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Figure 89. Plot of the default values for the Deposition Fraction from Diffusible Plasma to 

Brain parameter. 

5.2.27 COMPONENTS OF THE CIRCULATORY SYSTEM. 

The fraction of lead in Bound Plasma that is transferred to Red Blood Cells is the Deposition 

Fraction. Red blood cells have a high affinity for lead, and therefore a high percentage of the 

lead in blood is bound to the red blood cells. These cells, which have a half life of about 120 

days may also serve as a mechanism for eliminating lead from the system. The fraction of lead 

that is deposited in Extra Vascular Fluids from Diffusible Plasma and Red Blood Cells is 0.5, or 

50%. The Ratio of Total Extravascular Fluid mass to mass of blood Plasma is 3. The transfer of 

lead from diffusible plasma is on the order of 1-2/min, or 2000/day. The deposition fraction for 

Plasma Proteins is extremely small, 0.0004. The rate of loss for Plasma Proteins is 0.139/day; 

approximately 14 % of the lead in plasma proteins is transferred to other compartments per day. 

The amount of Red Blood Cells in the Reference Adult Male is 22 deciliters. The amount of 

Blood Plasma in the Reference Adult Male is 30 deciliters. 

5.2.28 TRANSFER RATE FROM RBC TO PLASMA. 

Age-dependent variable that represents the daily transfer of lead from Red Blood Cells to Plasma 

are shown in Figure 90. 
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Figure 90. Age-dependent variable for the Transfer Rate from RBC. Data are plotted on 

Figure 91. 

Figure 91. Plot of the default values for the Transfer Rate for RBC parameter. 

5.4.29 AMOUNT OF BLOOD. 

Total volume, in deciliters, of blood, which is age-dependent, is shown in Figure 92. 
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Figure 92. Age-dependent variable for total volume of blood (deciliters) Data are plotted 

on Figure 93. 

Figure 93. Plot of the default values for the Amount of Blood parameter. 

5.2.30 CHELATION FACTORS 1, 2, and 3. 

These chelation factors are not currently used. They were a part of the original Leggett model 

because chelation data were used at that time. The options are included against the possibility 

they might have some future use. 
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SECTION 6. CONTROLLING THE MODEL OUTPUT 

6.1. A SIMPLE CONFIDENCE TEST 

At this point, it is helpful to begin developing your familiarity with the model. First, observe the 

model output in the case where no changes have been made to the model defaults. Restart the 

model and select the option to “Create and new study.” Click on “Youth” to populate the age 

ranges through 13 years of age. Click Run, then OK to save the file; specify a new file named 

First Flight, and save this file; click “Exposure” and “Absorption,” then “Continue” “Start” and 

“Continue” to run the model with all default settings. Select “Plot” to produce the graph shown 

in Figure 94. This is a plot of the predicted blood lead concentration trough 4700 days, or 

thirteen years. Note that when only one parameter (Blood Pb) is plotted, the X and Y values are 

given as well. 

Figure 94. Output with all default settings 

 

Now return to the opening window by closing out two windows in succession, and change the 

exposure by selecting Media Exposure and clicking Edit. Click edit again to get to the parameter 

array for Air. Click the Dust tab and change the lead concentration of dust ingested by a toddler, 

preschooler and youth from the default 200 μg Pb/g to 2000 μg Pb/g. Click OK and run the 

model as before. You should get: 
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Figure 95. Total Blood lead with elevated dust lead exposure. 

Note that the Y-axis scale has changed to accommodate the range of values. While it appears 

that the effect of the increased exposure lasts only through 1900 days, the upper bound for the 

youth age range, a closer look will show that the blood lead concentrations will remain elevated 

throughout the next age range, adolescent, as the lead is recycled through other body tissues, 

including bone tissue, returning sometime later to the blood. Indeed, even at age nineteen, six 

years after the secession of the elevated lead exposure, the blood lead for the elevated exposure 

child is still about 15% higher than the child with the lower exposure. 

Take a moment to look at other body tissues to become familiar with the way the model 

distributes the lead over the various compartments throughout the lifetime of the individual. 

Remember that, as an experienced modeler, you will become adept at tweaking the biokinetic 

parameters according to information that you may have from your own studies, or to test the 

reality of data published by others. 

After editing the biokinetic parameters, close this option [X] and click RUN from the Primary 

window. The Model Run window appears next and offers you a choice of Exposure, 

Absorption, and Biokinetics. Click on any of these for which you want to see the output. 

Clicking on Absorption automatically triggers Biokinetics. Click CONTINUE and the Exposure 

Model Processing window appears. Click START. The processing time depends on the 

complexity of your inputs. The three options for historical diet, air and dust lead concentrations 

are under development and are not functional at this time. 
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There is an option on the Exposure Model Processing window to select the exposure model 

output file to view or bypass this step. This is fully optional and is if value if you are 

troubleshooting the model. The *.mod file gives you a view of the stepwise values you have 

selected. This file can contain over 32,000 lines and may take a few moments to generate. The 

*.mpa file gives you the total exposure μPb for each age range. Both of these files may be 

exported to a spreadsheet. 

The next window allows you to view the Exposure model output files using different extensions 

for the same file name that you have designated. 

Filename.mpa (Exposure Model Output by Age) gives the total amount of lead to which the 

modeled person was exposed by the six different routes. All of these should be listed by the age 

category. 

6.2. BIOKINETIC OUTPUTS 

6.2.1 TABLES 

CLOSE on the Select window runs the model. The outputs are saved to the same location as that 

for the input files. In the example below, the output is for 100 day intervals as stipulated in the 

Primary window, Simulation time step 100 day(s). 

An explanation of the various outputs and units are given in Table 2. 

6.1.2 PLOTTING 

Click PLOT on the window generates a default color plot of several parameters versus days. 

PRINT provides a copy of the chart. 
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Figure 96. Using the Built in Graphic Feature.

6.1.3 EDITING THE CHART 

Click EDIT allows for several options. 

In the Editing Window, SERIES, ticking (or unticking) a box will automatically adjust the chart. 

a. Axis: (i) Unticking Automatic allows changes to the scales. For example, the Maximum and 

Minimum ranges can be changed for the Y-(Left) axis and the number of decimal places. 

(ii) NOTE: The number of decimal places cannot be changed on the X- (Bottom) axis. 

(iii) Titles can be added to the Y-axis and also the X-axis. However, the default title for X-axis 

(‘Days’ in blue color) remains. This can be removed by going into Editing Titles, scrolling down 

from TITLES to FOOT and deleting ‘Days’( Fig. 39). 

(iv) The frequency of Ticks can be changed. 

(v) The main title can be edited in TITLES. For example, change Font size and Back Color. 

However, even though the title states it is black, the Black color needs to be clicked to achieve 

this (otherwise it stays yellow). 

(v) The background blue can be changed to white in PANEL by making START and END colors 

white. 
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(vii) To change output style for each parameter, for example, YCORT, go to EDITING, 

CHART, SERIES, click on the color square, in Color Window change to desired color, click 

OK, click on BORDER, in the window Border Color Editor, change Style, Click OK. 

Change other parameters in the same way. PRINT chart. 
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7.0 REFERENCES 

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