United States
Environmental Protection
Agency
National Center for
Environmental Assessment
Research Triangle Park, NC 27711
EPA/600/R-05/102
October 2005
Research and Development
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
NCEA
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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 l,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 3 7: 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 57
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 5$
Figure 75: Plot of the default values for the deposition fraction of lead in the brain 5$
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 multi-
compartmental 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
Install Shi eld 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, DEMOl.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.
EPA/6COK.-05013
Ofik* of
National Center For Environmental Assessment
All Ages Lead Model
Version: 1.05 Date Created: 09/11/2005
DISCLAIMER
Close this screen
automatically
This software represents ,i |>i eliminary effort by the U.S. Environmen-
tal Pi otection Agency. It is being cii ciliated f01 inter nal i eview and
evaluation purposes only .mil should not l>e used in conjunction with
,i non-hypothetical assessment until it has been officially released by
the Agency. At that time, full guidance and technical support docume-
ntation for the model's intended use and application will l>e pi ovided.
DRAFT: DO NOT CITE, QUOTE, COPY,
or DISTRIBUTE
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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Select Action - AALM
What would you like to do?
Action
C" Create a new study
'••" Open an existing study
|~ Don't ask me this again
You can create or open a study at any
time from the File menu or from the Tool
Bar.
OK
Cancel
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.
Options
Startup Preferences
Close the opening screen automatically
Display the Select Action dialog box after the opening screen
Default Directories
Data: CAPROGRAM FILES W\LM
Definition Files: CAPROGRAM FILES\AALMVDefFiles
OK
Cancel
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 Demol.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 Demol.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.
01. Untitledl
P Male r Female
Age Range Category
f Prenatal
17 Postnatal
[7 Toddler
17 Preschool
R Youth
[7 Adolescent
17 Young Adult
17 Middle Age
17 Early Retirement
>/ Late Retirement!
| End Date _^J
Age Range (days)
-155toO
[l to [183
[l84 to (1460
|1461 to (21 90
[2191 to |4745
|4746 to |6935
6936 to 14600
1 14601 to 1 23725
1 23726 to |29930
(29931 to (32850
- n[xj
7/29/2005 T
Age Range [yrs)
<0
0.0 to 0.5
0.5 to 4.0
4.0 to 6.0
6.0 to 13.0
13.0 to 19.0
19.0 to 40.0
40.0 to 65.0
65.0 to 82.0
82.0 to 90.0
|[T~ ~ |Day(s) ,
Date Ranges
08/22/1915-02/20/1916
02/21/1916-08/20/1919
08/21/1919-08/19/1921
08/20/1921 -08/17/1928
08/13/1928-08/16/1934
08/17/1934-08/11/1955
08/12/1955-08/04/1980
08/05/1980-07/31/1997
08/01/1997-07/29/2005
3
-Sc
Mat
Res
Res
Res
Res
Res
Res
Res
Res
Res
| Media Exposure ^
ernal
dential
dential
dential Daycare
denial. Recreational School
dential Recreational School
dential Recreational Occupational
dential Recreational Occupational
dential Recreational
dential
Edit |
Run
Insert Event
Defaults
Clear All
Close
Help
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 Demol 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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12. Model Run
Exposure
Absorption
Biokinetics Edit Model Settings
Continue
Cancel
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 V). Press Continue to get the next screen.
12a. Exposure Model Processing
Processing Study File . ..
Start
Cancel
0%
Show Exposure Results l~~ Use Historical Diet Pb Concentration
I Use Historical Air Pb Concentration
| Press [Start] button to run process, [Cancel] to stop. |- Use Historical Dust Pb Concentration
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.
12b, Select
Select the exposure model output file to view.
DEMOLrnod
DEMQLmpa
View
Continue
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:
121. Biokinetks Output File - C:\Program
Files\AALM\DEM01.mob "^
1
2
3
4
S
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Days
Blood
100.00 59.57320730
200.00 74.99385985
300.00 87.52161683
400.00 92.66780516
500.00 93.95207832
600.00 96.95696595
700.00
800.00
900.00
1000.00
1100.00
1200.00
1300.00
1400.00
1500.00
1600.00
1700.00
1800.00
1900.00
2000.00
2100.00
2200.00
2300.00
100.5488671
104.3684032
108.3233116
112.4094359
116.6512371
121.0825655
125.7409657
130.6665373
120.7866609
117.6172172
119.0561251
122.0980072
123.7529231
125.1638764
127.2397138
126.0974126
115.9016073
Cortical
620.7635935
1014.870227
1068.310926
1102.618125
1137.706059
1178.948697
1218.005640
1253.168382
1284.685231
1313.288044
1339.745199
1364.743795
1388.873538
1412.639076
1415.891046
1380.196595
1360.012449
1349.402495
1348.450382
1357.137548
1372.120817
1390.575201
1375.607222
Trahecular
155.1908984
253.7175567
267.0777316
275.7683800
285.4432296
297.0188847
308.1954584
318.4629236
327.8326323
336.4502432
344.4785205
352.0649610
359.3356916
366.3969987
367.6363811
357.8301706
352.0897615
348.8150850
348.1877407
350.5088979
354.8038135
360.2104014
355.7690429
Liver
84.05649215
134.6291828
159.2715834
185.7980257
192.2514812
196.2516904
199.0910815
201 .2287977
202.8755518
204.1488684
205.1256620
205.8612626
206.3972082
206.7650919
196.6072323
1182.1601065
174.0447650
168.7021013
165.2048646
163.6887077
163.7381440
163.8271536
153.6127219
Export to | T|
3
0
Plot Plot fit Fetus Close
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 (|ig/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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Gender
f* JMdd '"" Female
Computation at
End Date
7/28/2005 _J
Age Range Category Age Range (days)
f Prenatal
F Postnatal
T Toddler
F Preschool
F Youth
r Adolescent
r Young Adult
r Middle Age
f~ Early Retirement
r Late Retirement
•155 to 0
~~ to[o~
~ to[o~
~~ to[T
~ tofiT
to fT
~ to[o~
~to[T
~~ tofiT
~" to[o~
Age Range (yrs) Date Ranges
<0
0.0 to 0.5
0.5 to 4.0
4.0 to E.O
6.0 to 13.0
13.0 to 19.0
19.0 to 40.0
40.0 to 65.0
65.0 to 62.0
82.0 to 90.0
Parameters
Parameters
|Media Exposure T]
Scenarios—
Maternal
Residential
Residential
Residential Daycare
Residential Recreational School
Residential Recreational School
Residential Recreational Occupational
Residential Recreational Occupational
Residential Recreational
Residential
Run
Insert Event
Defaults
Clear All
Close
Help
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.
The Prenatal option is not fully implemented but is included for demonstration purposes. (See Section 4)
9/27/2005
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15
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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.
E3J 1 Until Ied1
C Male <* Female
l~" Prenatal
|7 Postnatal
R Toddler
I? Preschool
|7 Youth
|7 Adolescent
|7 Young Adult
|7 Middle Age
|7 Early Retirement
W Late Retirement
t
I
I
| End Date
jj J
_lJ
anuary, [
1/20/2006 "V]
2006 H-H>- I
25 26 27 28 29 30 31
1234567
8 9 10 11 12 13 14
15 16 17 18 19 20 21
22 23 24 25 26 27 28
29 30 31 1
^5 Today: 9/24/2005
4746 to
6936 to
14601 to
23726 to
29931 to
6935
14600
23725
28930
32350
13.0 to 19.0
19.0 to 40.0
40.0 to 65.0
65.0 to 82.0
82.0 to 90.0
P~~ |DaV(s)
TS) Date Ranges
02/13/1916-08/13/1916
08/14/1316-02/11/1320
02/12/1920-02/10/1922
02/11/1922-02/08/1929
02/09/1929-02/07/1935
02/08/1935-02/02/1956
02/03/1 956 - 01 /26/1 831
01 /27/1 981 - 01 /22/1 898
01/23/1338-01/20/2006
3
uy
| Media Exposure _^j
Edit
t^
Maternal
Residential
Residential
Residential, Daycare
Residential, Recreational, School
Residential, Recreational, School
Residential, Recreational, Occupational
Residential, Recreational, Occupational
Residential, Recreational
Residential
Run
Insert Event
Defaults
Clear All
Close
Help
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.
The two youngest age groups do not have the Occupational option, and therefore have only three location options.
9/27/2005 DRAFT: DO NOT QUOTE OR CITE 16
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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.
9/27/2005 DRAFT: DO NOT QUOTE OR CITE 17
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All Ages Lead Model - DEM01 .xal
File Edit View Parameters Run Tools Window Help
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.
\St A" Ages Lead Model - C:\Program Files\AALM\Review 22.xal
File Edit View Parameters Run Tools Window Help
View Results
Set Output
Plot Multiple MOB
Figure 12. Tool Selection Menu. Click on 'Set Output'.
Set Output
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Output
Sigma
Plasma
RBC
Blood
Skeleton
Cortical
Trabecular
Liver
Kidney
Soft
Brain
Lung
Urine
Feces
Total Body2
Total Excretion
Bone Fraction
Brain Fraction
Liver Fraction
Blood Fraction
Renal Fraction
Other Fraction
Blood Concentration
RBC Concentration
Cancel
Selected?
n
D
n
El
n
EI
El
El
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
r~i
OK '
-
V
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.
9/27/2005
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18
-------
r
3n
r. U£nionstr/ Late Retirement
,
(End Date _^_
•155 to 0
pj to |183
[lS4 to |1460
1 1461 to 1 21 90
2191 to 1 4745
[4746 to | 6935
| 6936 to | 14600
1 14601 to 1 23725
1 23726 to 1 29930
] 29931 to 1 32850
7/29/2005 _^_
<0
0 0 to 0 5
0.5 to 4.0
4.0 to 6.0
6.0 to 13.0
13.0 to 19.0
19.0 to 40.0
40.0 to 65.0
65.0 to 82.0
82.0 to 90.0
|1 |Dflrit) .
08/22/1 91 5 - 02/20/1 91 6
02/21/1916-08/20/1919
08/21/1919-08/19/1921
08/20/1921 -08/17/1928
08/18/1928-08/16/1934
08/17/1934-08/11/1955
08/12/1955-08/04/1960
08/05/1980-07/31/1997
08/01/1997-07/29/2005
| Media Exposure •»•
Maternal
Residential
Residential, Daycare
Residential Recreational School
Residential, Recreational, School
Residential, Recreational, Occupational
Residential, Recreational Occupational
Residential, Recreational
Residential
QlsJB
Edit
Rm |
Insert Event
Defaults
Clear All
Close
Help |
Figure 14: Primary window with full specifications for model run, ready for entering
exposure parameters.
AALM
5ave current study changes?
OK
Cancel
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.
9/27/2005
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19
-------
Set the parameter window to "Media Exposure" and click the EDIT button. There are two
options in Window la: "Exposure Parameters" and "Historical Exposure Settings." At this time,
select "Exposure Parameters" to gain access to Window lal: 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 (jig Pb/m3) and amount of air inhaled (mVday)
for each exposure component: outdoor, residential, school, and occupational. In this way, air
exposure is calculated as the product of the two parameters |ig/m3 and m3/day, giving ng/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.
1a. Select Exposure Parameter To...
I Exposure Parameters ^| Edit
Cancel
Figure 16. Select Exposure Parameters to review and modify the exposure portion of the
model.
9/27/2005 DRAFT: DO NOT QUOTE OR CITE 20
-------
1a1. Media Exposure
Air | Diet | Dust | Water | Pica | Dermal ]
Parameter
Start Date
Duration (days)
Postnatal
08CK191S
182
Outdoor Air Lead Cone. (ug/m3) ||0.1
Residential Air Prj Cone. (% of outdoor) 1 30
School Air Pb Cone. (% of outdoor)
Occupational Air Pb Cone. (% of outdoor)
Residential Ventilation Rates (m3/h)
School Ventilation Rates (mSrti)
Occupational Ventilation Rates (m3jh)
Recreational Ventilation Rates (m3/h)
30
30
0.37
0.37
0
0.65
Toddler
02MM916
1276
0.1
99
88
30
0.37
0.37
0
0.65
Preschool
08COfl919
729
0.1
65
50
30
0.47
0.47
0
1.74
Youth
08(19(1921
2554
0.1
30
30
30
0.5
0.5
0
1.9
Adolescent
08(17(1928
2189
0.1
30
30
30
0.53
0.53
0
2.4
Young Adult
08(16(1934
7664
0.1
30
30
30
0.55
0.55
3.4
2.6
Middle Age
08(11(1955
9124
0.1
30
30
30
0.55
0.55
3.4
2.6
Early Retirement
08(04(1980
6204
0.1
30
30
30
0.55
0.55
2.5
2.5
Late Retiremen
07(31 ft 997
2919
0.1
30
30
30
0.48
0.48
1.33
1.33
Use Historical Air Pb Concentration
Clear Clear All Default | All to Default
OK | Cancel
Help
Figure 17: Exposure options group with Air component ready for review and
modification.
The default value of outdoor air is 0.1 jig 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.htmltffca
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
9/27/2005 DRAFT: DO NOT QUOTE OR CITE 21
-------
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.
A
r Diet
| Dust
Water ] Pica
Parameter
Start Date
Dermal |
Postnatal | Toddler
Preschool
Youth
Adolescent
Young Adult | Middle Aye| Early Retirement
1 08/22/1 91 5 02/21/1916 08/21/1919 03/20/1921 08/18/1928 08/17/1934
Duration (days)
Market Fruit Intake [g/day]
Market FruS Pb Cone, [ug/g]
Market Vegetable Intake [g/day]
Market Vegetable Pb Cone, [ug/g]
Market Meat Intake [g/day]
Market Meat Pb Cone.
[ug/g]
Market Fish Intake [g/day]
Market Fish Pb Cone, [ug/g]
182 1276 1 729 2554 |2189 7664
13
1 55
0.01 0.01
70
70
0.01 0.01
20.2 75.4
0.01 0.01
6.1
8
0.01 0.01
60
0.01
82
0.01
85 .6
0.01
12.2
0.01
70
0.01
113
0.01
115
0.01
18.1
0.01
75
0.01
150
0.01
145
0.01
20
0.01
75
0.01
160
0.01
160
0.01
22
0.01
| Market Die
Clear
08/12/1955 08/05/1980
9124 6204
85
0.01
170
0.01
160
0.01
22
0.01
Late Retirement
08W/1997
2919
85
0.01
170
0.01
150
0.01
20
0.01
70
0.01
160
0.01
130
0.01
20
0.01
^| + | J |~ Use Default Historical Pb Concentrations
Clear All | Default All to Default
|Gardn Fruit lntake[S dietj^J|
OK
Cancel I
Set Del. |
Help
Figure 18: Options for Dietary exposure.
soldered side seams. Air lead concentrations have also decreased, reducing the amount of lead in food crops.
9/27/2005 DRAFT: DO NOT QUOTE OR CITE 22
-------
1a1. Media Exposure
A
Diet
Dust | Water | Pica | Dermal
Parameter
Start Date
Duration (day
s)
Market Frurt Intake [g/day]
Market Frurt Pb Cone, [ug/g]
Market Vegetable Intake [g/day]
Market Vegetable Pb Cone, [ug/g]
Market Meat Intake [g/day]
Market Meat Pb Cone, [ug/g]
Market Fish Intake [g/day]
Market Fish Pb Cone, [ug/g]
Garden Frurt Intake [% ot diet]
Garden Fruit Pb Cone, [ug/g]
Garden Vegetable Intake [% of diet]
Garden Ve
getablePb Cone, [ug/g]
Postnatal
1 0/01 /1 91 5
182
13
0.01
70
0.01
20.2
0.01
6.1
0.01
0
0.01
0
0.01
Toddlei
04/01/1916
1276
55
0.01
70
0.01
75.4
0.01
8
0.01
0
0.01
0
0.01
Preschool
09/30/1919
729
60
0.01
92
0.01
85.6
0.01
12.2
0.01
0
0.01
0
0.01
Youth
09/29/1 921
2554
70
0.01
113
0.01
115
0.01
18.1
0.01
0
0.01
0
0.01
Adolescent
09/27/1928
2189
75
0.01
150
0.01
145
0.01
20
0.01
0
0.01
0
0.01
Young Adult
09/26/1934
7664
75
0.01
160
0.01
160
0.01
22
0.01
0
0.01
0
0.01
Middle Age
Early Retirement
09)21.'19S5 09/14/1980
9124
85
0.01
170
0.01
160
0.01
22
0.01
0
0.01
0
0.01
6204
Late Retirement
09/10/1997
2919
85 1 70
0.01
170
0.01
150
0.01
20
0.01
0
0.01
0
0.01
0.01
160
0.01
130
0.01
20
0.01
0
0.01
0
0.01
iHomeGarden ^t\
Clear
Clear All | Default
_^J r~ Use Default Historical Pb Concentrations
All to Default |
| Gardn Fruit lntake[% d et_J |
OK |
Cancel
Set Def. |
Help
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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23
-------
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 jig Pb per area sampled (|igPb/cm2);
a dry vacuum sample can give jig 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.
1a1, Media Exposure
Air | Diet Dust Water j Pica ] Dermal |
Parameter
Start Date
Duration (days)
Total Dust Ingested [mg/day]
Residential Dust Pb Cone [ug/g]
Postnatal
Toddler
08G2/191S 02/21/1916
182 1276
40
200
Residential Dust (Core
_d r u
35
200
Preschool
08/21/1919
729
135
200
Youth
08/20/1921
2554
85
200
Adolescent
08/18/1928
2189
50
200
Young Adult| Middle Aye
08/17/1934
7664
40
200
08/12/1955
9124
40
200
Early Retirement
08/05/1980
6204
40
200
Late Retiren
08/01 /1 997
2919
30
200
is Historical Dust Pb Concentration
OK
Cancel
Help
Clear Clear All | Default | All to Default |
Figure 20: Exposure options for dust exposure.
The choice between the concentration method (Cone) (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 [Cone] 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
9/27/2005
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24
-------
1a1. Media Exposure
A
Diet
Dust
Water
Pica | Dermal |
Parameter
Start Date
Duration (days)
Total Dust Ingested [mg/day]
Residential Dust Ingested [% Total]
Residential Dust Pb Cone [ug/g]
School Ingested Dust [%]
School Ingested Dust Pb Cone
ug/g]
Occupational Ingested Dust [%]
Occupational Ingested Dust Pb Cone [ug/g]
Recreational Ingested Dust [%]
Recreational Ingested Dust Pb Cone [ug/g]
Postnatal
Toddler
Preschool
Youth
Adolescent
Young Adult
Middle Aye
Early Retirement
08(22/1915 02/21/1916 08/21)1919 03/20/1921 08/18/1928 08/17/1934 08/12/1955 08/05/1980
182 [1276 729 2554 2189 7664 9124 6204
40 J85 135 JS5 JSO 40 |40
100
200
0
0
0
0
0
200
100
200
0
0
0
0
0
200
100
200
0
0
0
0
0
200
SO
200
20
0
30
0
0
200
50
200
20
0
30
0
0
200
50
200
20
0
30
0
0
200
40
SO
200
20
0
30
0
0
200
50
200
20
0
30
0
0
200
Late Retiren
08/01/1997
2919
30
50
200
20
0
30
0
0
200
Other Dust Sources (Core)
Clear
Clear All I
~3 ru
se Historical Dust Pb Concentration
Default | All to Default |
OK Cancel
Help
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 drop-
down window.
['all Media ExpOSUIe
Air | Diet Dust | Water ] Pica | Dermal ]
Parameter
Start Date
Duration (days)
Total Contact Surface Area [m2/day]
Residential Dust Pb Loading [ug/m2]
Postnatal
Toddler
Preschool
08/22/1915 02/21/1916 OS/21/1919
182
0.06
135
1276 729
0.13
135
Residential Dust (Area) j-j T U
0.2
135
Youth
Adolescent
08/20/1921 08/18/1928
2554 12189
0.13
135
0.07
135
Young Adult
08/17/1934
7664
0.06
135
Middle Age
Early Retirement
08/12/1955 08/05/1980
9124 6204
0.06
135
0.06
135
Late Retiren
08/01/1997
2919
0.04
135
se Historical Dust Pb Concentration
Clear Clear All | Default | All to Default |
OK
Cancel Help
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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I-:il Media Exposure
Ai
| Diet Dust
Water
Pica
Dermal |
Parameter
Start Date
Duration fdavs)
Total Contact Surface Area
[m2/day]
Residential Contact Surface Area [% Total]
Residential Dust Pb Loading [ug/m2]
School Contact Surface Area [% Total]
School Dust Pb Loading [ug/m2]
Occupational Contact Surface Area [% Total]
Occupational Dust Pb Loading [ug/m2]
Recreational Contact Surface Area [% Total]
Recreational Dust Pb Loading [ug/m2]
Postnatal
To.MI.ii
Preschool
Youth
Adolescent | Young Adult I Middle Age] Eai ly Retii emeivt | Late Retii en
08/22/191502/21/191608/21/191908/20/192108/18/1928 03/17/1934 08/12/1955
182 1276 729 2554 2139 7664 9124
0.06 0.13 0.2 0.13 0.07 0.06 0.06
100
135
0
0
0
0
0
0
100
135
0
0
0
0
0
0
100
135
0
0
0
0
0
0
100
135
0
0
0
0
0
0
100 100 100
135 135 135
000
000
000
000
000
000
Other Dust Sources (Area) _^J
Clear Clear All
P Use Historical Dust Pb Concentration
Default | All to Default |
OK
03/05/1980 08/01/1997
6204 291 9
0.06 0.04
100 100
135 135
0 0
0 0
0 0
0 0
0 0
0 0
| Cancel Help
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 jig Pb/L x L/day = jig 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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1a1, Media Exposure
A
Diet ] Dust Water | pjca
Parameter
Start Date
Duration (days)
Total Vol. of Water Consumed [L/day]
Flushed Pb Cone [ugJL]
Dermal
Postnatal
08/22/1915
182
1
5
Flushed Water
Clear Clear All
3
Default
Toddler
Preschool
02/21/1916 08/21/1919
1276 [729
1
5
1
5
Youth
08/20)1921
2554
1
5
Adolescent
08/18/1928
2189
1
5
Young Adult | Middle Age
081-17/1934
7664
1
5
08/12/1955
9124
1
5
J All to Default
Early Retir ement
08/05/1 980
6204
1
S
Late Retii ement
08/01 /1 997
2919
1
5
OK | Cancel
Help
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.
1a1. Media Exposure
Ai
| Diet
Dust Water
Pica
Parameter
Start Date
Duration (day
s)
Total Vol. of Water Consumed [L/day]
Flushed Atnt [% of Total Volume]
Flushed Pb Cone [ug.'L]
First Draw Tap Amt [% of Total Volume
First Draw
TE
p Pb Cone. [ug/L]
Fountain Amt [% of Total Volume]
Fountain Pb Cone [ug/L]
Bottled Amt [% of Total Volume
Bottled Pb Cone [ug/L]
Dermal ]
Postnatal
Toddlei
Preschool | Youth
Adolescent
Young Adult | Middle Age| Early Retiremeivt
08/22/191502/21/191608/21/191908/20/192108/18/1928 08/17/1934 08/12/1955
182 |l276 |729 |2554 i2189 7664 9124
1
84
5
5
4
10
7
1
4
1
84
5
5
4
10
7
1
4
1
84
5
5
4
10
7
1
4
1
84
5
5
4
10
7
1
4
1
84
5
5
4
10
7
1
4
1
64
5
5
4
10
7
1
4
1
84
5
5
4
10
7
1
4
Late Retii ement
08/05/1980 08/01/1997
6204
1
84
5
5
4
10
7
1
4
2919
1
84
5
5
4
10
7
1
4
Other Water Sources
Clear
Clear All
o
Default
All to Default |
OK | Can
;el Help
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.
1 b. Activity Patterns
p
ostnatal | Toddler | Preschool Youth | _L
Environment | Weekly Hours] % Inclooi
Residential
School
Occupational
Recreational
Weekly Total
168.0 90.0
cm
0.0
0.0 0.0
163.0
_t
Daily sleep hours: 12.0
OK Cancel
I
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.
12. Model Run
[• Exposure
|~~ Absorption
|~~ Biokinetics Edit Model Settings
Continue Cancel
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.
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Select the exposure model output file to view.
Reviewl.mpa
View
Continue
Figure 28. Two files are available for review, *.mod and *.mpa.
2<* Exposure Model Output by Day(s) - Reviewl mod
1
2
3
4
5
6
7
8
9
10
<
Interval Start Date
Interval End Date
Time Step (Day)
Airing Pb;TS)
09121997 09092005 1 I 0.3859
09121997 09092005 1 0.3859
09121997 09092005
09121997
09121997
091 21 997
09121997
09121997
09121997
09121997
09092005
09092005
09092005
09092005
09092005
09092005
09092005
1
1
1
1
1
1
1
1
0.3859
0.3859
0.3359
0.3859
0.3859
0.3859
0.3859
0.3859
Dieting Pb/TS)
Watering Pb/TS)
Dusting Pb/TS)
DermaHug/T •"»
3.8000 420.0000 6.0000 0.00(
3.8000 420.0000 ~ 6.0000 ~ 0001
3.8000
3.8000
3.8000
420.0000
420.0000
420.0000
3.8000 420.0000
3.8000 420.0000
3.8000 420.0000
3.8000 420.0000
3.8000
420.0000
6.0000
6.0000
6.0000
6.0000
6.0000
6.0000
6.0000
6.0000
Illl
0.001
O.OOC
O.OOC
0.00(
0.00!
O.OOC
0.00(
o.OQ(r7|
"ffi
Export to
Figure
1
29. Line by line output for the exposure module. *.mod
OK
1. Exposure Model Output by Age - Reviewl .mpa
Age Category
Postnatal
Toddler
Preschool
Youth
Adolescent
Young Adult
Middle Age
Early Retirement
Late Retirement
Airing Pb)
59
1124
580
1997
2002
10175
1 0001
4404
1126
Dieting Pin
Watering Pb)
1 98 76440
2659 535920
1821
8073
8537
31958
39871
26366
11092
3061 80
1072680
919380
3218830
3832080
2605680
1225980
Dusting Pb)
Dermallng Pb)
1456 0
21692 0
19683
43418
21890
61312
72992
49632
17514
0
0
0
0
0
0
0
Picaing Pb)
0
0
0
0
0
0
0
0
0
Export to
OK
Figure 30. Total exposure by age for each exposure category (*.mpa)
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•* 1 - t ul
1
2
3
4
5
6
7
S
9
10
11
12
13
14
15
16
17
18
19
20
21
22
<\
t Model Settings
Parameters
Exposure Age
Last Day
Maximum Cycles
Fetal Exposure On/Off
Fixed Length Delta Option
Delta Step Lengths
Output Step Interval
AcuteChronic
Mode of Intake
LinearMonlinear Model
RBC Threshold Concentration
Nonlinear Parameter 2
Power
Chelation On/Off
Fixed Delta
Body Size Curve (on/off)
Bone Computation?
Values
0.002740
32850
32850
0
0
Edit
100
2
3
1
60
350
1.5
0
1.0
0
Use Leggett
Default
Units
years
days
days
ug/dl
days
»
|
Descriptions
Age at acute exposure or beginning of chronic exposure
Maximum number of days
Maximum number of cycles
Fetal Exposure Switch (1=On 0=Off) INTERNAL
Use fix length delta (0=Variable sOFixed/TimeStep)
Delta step lengths by age range
VWite output to file only on these steps
Switch for acute or chronic (1=Acute 2=Chronic)
Selection for mode of intake (0=lnjection 1 =lnhalation 2=lngestion 3=Combination
(0= Linear Model 1 =Nonlinear Model)
Lead concentration on RBC above whic,T a nonlinear model is used
Nonlinear Parameter 2
Power
Chelation Switch (0=0f f 1 =0n)
Length for Fixed Delta
Computation will use growth curve (1=on, 0=off)
Bone computation to be used (i.e. Leggett or O'Flaherty)
Save
Keys
expage
endday
ncycle
ifetal
deltO
delta
iskip
iacute
inmode
irbc
rtacnl
satrat
power
ichel
deltfix
bUseBodySi
sBoneComp
H
Cancel
L
A
v
J
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.
1a1. Media Exposure
A
r ] Diet
Dust ] Water Pica | Dermal
Parameter
Start Date
Duration (days)
Lead Cone
of Soil (ug/g)
Soil Ingested (a/day)
Lead Cone
of Paint Chip (ug/cm2)
Paint Chip Ingested (cm2/day)
Postnatal
08/22/1915
1S2
200
0
500
0
Clear
Cleat All Default
Toddler
02C1/1916
1276
200
0
500
0
Preschool
08(21 fl919
729
200
0
500
0
Youth
08/20/1 921
2554
200
0
500
0
Adolescent
08/18/1923
2189
200
0
500
0
Young Adult
08/1 7/1 934
7664
200
0
500
0
Middle Aye
Early Retirement
08/1 2/1 955 08/05/1 980
91 24 6204
200
0
500
0
200
0
500
0
All to Default |
OK
Late Retirement
08/01/1997
2919
200
0
500
0
Cancel Help
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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32
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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.
I
-------
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 micro-
site 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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Non-
Exchange
Non-
Exchange
Volume
! Exchange
ar Volume
I Exchange
—
Cortical
Surface
>
>
Trabecular
Surface
Diffusible
Plasma
.11
Extra-
Vascular
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.
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6. Edit Values for Delta Step Lengths
Description: | Delta step lengths by
1
2
A
Age Cut-off
Delta Step Lengths
Import Data Export Data
age range Interpolation Type: | Linear -»-| Unit:
BCD
1 000 1 900 2800
1 .0 1 .0 1 .0
Add Column Delete Column
E
6700
1.0
Plot
F
21900
1.0
Save | Cancel
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.
worption y
Parameters
;rmal Absorption Factor
ng Compartment 1 Fraction
ng Compartment 2 Fraction
ng Compartment 3 Fraction
ng Compartment 4 Fraction
ng Compartment 1 Rate
ng Compartment 2 Rate
ng Compartment 3 Rate
ng Compartment 4 Rate
Absorption Fraction
site of Movement thru Gl Tract
action to Gl
omach Transfer Rate
nail Intestine Transfer Rate
jper Large Intestine Transfer Rate
wer Large Intestine Transfer Rate
Values
0
0.25
0.35
0.3
0.1
16.6
5.54
1.66
0.347
Edit
Edit
0.04
24
6
1.35
1
Units
Descriptions I Keys
Dermal absorption factor should be between 0 to 1 with 0 as default
Fraction of Pb deposited amount assigned to lung compartment 1
Fraction of Pro deposited amount assigned to lung compartment 2
Fraction of Pb deposited amount assigned to lung compartment 3
Fraction of Pb deposited amount assigned to lung compartment 4
/day
/day
/day
/day
Transfer rate from lung compartment 1
Transfer rate from lung compartment 2
Transfer rate from lung compartment 3
Transfer rate from lung compartment 4
| Gastrointestinal absorption fraction
/day
Scales rate of movement through the gastrointestinal tract
Fractional movement to the gastrointestinal tract
/day
/day
/day
Adult transfer rate from stomach
Adult transfer rate from small intestine
Adult transfer rate from upper large intestine
/day Adult transfer rate from lower large intestine
Default
I
kdermal
r1
r2
r3
r4
br1
br2
br3
br4
af1
agscal
ciliar
rstmc
rsic
ruli
rlli
a
Save Cancel
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
10. Edit
Description: (Gastrointestinal absorption fraction
1
2
< | —
A
Age Range
Gl Absorption Fraction
Import Data Export Data
B
0.000 0.274
0.45 0.45
Illl
Add Column D
Interpolation Type: | Linear _rj Unit: I
C D E F G
1.000 5.000 10.000 15.000
0.3 0.3 0.3 0.3
D B
elete Column | Plot Save Cancel
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
0.662
0.612
0.562
SO .512
fe
S0.462
LJ_
SO .412
1.
o0.362
astrointestinal Absorption Fraction
o
0.262
091 9
0.162-
• •
1 1
• •
^\.
'"--.
-*_
i
1
i
T TI • m m
l-|— i — i— i— | — i— i— i — |— i — i— i— | 1 1 1 -r i i i T i ~ T
0.000 5.000 10.000 15.000 25.000 30.000 40.000 60.00
Age Range
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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11. Edit
Values for Rate of Movement thru Gl Tract
Description: Scales rate of movement through the gastrointestina Interpolation Type: | Linear
1
2
<
A
Age Range
Rate of Movement thru
Import Data
Export Data
B
0.000
1 .66667
Illl
C D E
0.274 1 .000 5.000
1 .66667 |l .66667 1 .66667
Add Column
I
Delete Column] Plot
I
_»J Unit: | /day
F G
10.000 15.000
|1 .33333 1
B
Save Cancel
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 |ig/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 Exposure-
default 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, l=inhalation, 2=ingestion,
3=combination; the default is combination and the model has not been tested for any other mode.
PARAMETER
Exposure age
Last Day
Maximum Cycles
Fetal Exposure
Fixed Length Delta Option
Delta Step Lengths
Output Step Interval
Acute/Chronic
Mode of Intake
Linear/Nonlinear
RBC Threshold Concentration
Nonlinear Parameter 2
Power
Chelation
Fixed Delta
Body Size Curve
Bone Computation
DEFAULT
VALUE
0.002740
32850
32850
0
0
EDIT
100
2
3
1
60
350
1.5
0
1.0
0
Use Leggett
TYPE
Function with default value
Function with default value
Function with default value
On/Off Switch
On/Off Switch
Drop down window with age-related
variables
Function with default value
On/Off Switch
On/Off Switch
On/Off Switch
Function with default value
Function with default value
Function with default value
On/Off Switch
Function with default value
On/Off Switch
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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C A ir /
Respiratory tract
1
OE Mm n a tio n pools of
the body
1 |B.dy..mp.rlm.n.
/D let, D u s t7^\
V^ Water )
\
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
1d1. Edit Model Settings @
•i
2
3
4
5
6
7
B
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Parameters | Values
Units | Descriptions
Keys
Exposure Age 0.002740 years Age at acute exposure or beginning of chronic exposure expage
Last Day 32850.000000 days Maximum number of days endday
Maximum Cycles
Fetal Exposure On/Off
Fixed Length Delta Option
Delta Step Lengths
Output Step Interval
Acute/Chronic
Mode of Intake
Linear/Nonlinear Model
RBC Threshold Concentration
Nonlinear Parameter 2
Power
Chelation CrtOff
Fixed Delta
Body Size Curve (on/off)
Bone Computation?
32350.000000
0
0
Edit
100
2
3
1
60
350
1.5
0
1.0
0
Use Leggett
Default
days
ug/dl
days
Maximum number of cycles
Fetal Exposure Switch (1=On 0=Off) INTERNAL
Use fix length delta (0=Variable sO=Fixed/TimeStep)
Delta step lengths by age range
Write output to file only on these steps
Switch for acute or chronic (1=Acute 2=Chronic)
Selection for mode of intake (0=lnjection 1 =lnhalation 2=lngestion 3=Com
(0= Linear Model 1 =Nonlinear Model)
Lead concentration on RBC above whcih a nonlinear model is used
Nonlinear Parameter 2
Power
Chelation Switch (0=Off 1 0n)
Length for Fixed Delta
Computation will use growth curve (1=on, 0=off)
Bone computation to be used (i.e. Leggett or O'Flaherty)
Save
ncycle
ifetal
deltO
delta
iskip
iacute
inmode
irbc
rbcnl
satrat
power
iohel
deltfix
bUseBodySiiE
sBoneComput
-
&
Cancel
Figure 42: Window for editing the model settings. Features other than the Delta Step
Length have options than do not vary with age.
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6. Edit Values for Delta Step Lengths
Description: 1 Delta step lengths by
A
1 Age Cut-off
2 Delta Step Lengths
Import Data Export Data
age range
B
1 000 1 90
1 .0 1 .0
Add Column
Interpolation Type: | Ceiling _^J Unit:!
C D E F
0 2800 6700 21900
|l.Q |l.O 1.0
Delete Column Plot Save Cancel
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).
1 d2. Edit Biokinetic Parameters
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Parameters
Pta Decay Rate
Cortical Bone Turnover
Trataecular Bone Turnover
Transfer from Cortical Surface to Blood
Transfer from Trabecular Surface to Blood
Cortical Surface to Volume Transfer
Trabicular Surface to Volume Transfer
Total Transfer from Exchange Bone Volume
Transfer from Exchange to Non-exchange Volume
Transfer from Liver 1
Transfer from Kidney 1
Transfer from Bladder to Urine
Transfer from Liver 2
Transfer from Kidney 2
Transfer from Fast Soft Tissue
Transfer from Intermediate Soft Tissue
Transfer from Slow Soft Tissue
Transfer Rates from Brain
Deposition Fraction in Urine
Deposition Fraction in Feces
Deposition Fraction in Sweat
Intermediate Soft Tissue to Excretion Fraction
Deposition Fraction in Bone
Default
Values
0
Edit
Edit
Edit
Edit
Edit
Edit
Edit
Edit
0.0693
0.139
Edit
Edit
Edit
2.079
0.00693
0.00038
Edit
0.015
0.006
0.0035
0.4
Edit
Units
/day
/day
/day
/day
/day
/day
/day
/day
/day
/day
/day
Descriptions
Rate of decay for Pb
Cortical bone turnover rate by age range
Trabecular bone turnover rate by age range
Transfer rate from the cortical surface to blood by age range
Transfer rate fortataecular surface to blood by age range
Fraction transfer from the cortical bone surface to the volume of I
Fraction transfer from the trabecular bone surface to the volume
Total transfer rate from exchange bone volume by age range
Fraction transfer from exchange volume to non-exchange volume
Transfer rate from liver 1
Transfer rate from kidney 1
A
Transfer rate from uninary bladder to urinary tract by age range
Transfer rates from liver section 2 by age range
Transfer rate to kidney section 2 by age range
Transfer from fast soft tissue 1 by age range
Transfer from intermediate soft tissue 2 by age range
Transfer from slow soft tissue 3 by age range
Transfer rates of lead from brain by age range
Deposition fraction in urine
Deposition fraction in feces
Deposition fraction in sweat
Fraction transfer from intermediate soft tissue to excretion
Deposition fraction in bone by age range
I- 1: _ J I. .1 :L: :_ .. A _ l.. _ I. .!_..!... _
Save
3
Cancel
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 DEC AY 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.
Other Soft Tissues
Rapid
Turnover
Kidneys
Other
Kidney
Tissue
Urinary
Path
11 <'
Bladder
Contents
30
14
38
31
Diffusible
Plasma
.afi.lt ,
I Extra- |
i Vascularj
P4H
i RBC i
I Bound
! Plasma
i
21
T
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
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2, Edit Values for Cortical Bone Tin novel
Description: Cortical bone turnover rate by age range
Interpolation Type: | Linear •*•[ Unit:
1
2
A
Age Range
Cortical Bone Turnover
B
0.000
0.0102
c
0.274
0.00822
D
1 .000
0.00288
<
E
5.000
0.00154
F
10.000
0.00089
G
15.000
0.00051;
>
Import Data Export Data
Add Column Delete Column
Plot
Save
1
Cancel
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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7. Edit Values for Trabicular Surface to Volume Transfer
Description: Fraction transfer from the trabecular bone surface to
Interpolation Type: | Linear
Unit:
1
2
Import Data Export Data Add Column Delete Column
Plot
Save
Cancel
Figure 48. Age specific values for Surface to Volume in Trabecular Bone. Data are plotted
on Figure 49.
Trabecular Surface to Volume
0.503 ••••
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
60.00
Figure 49. Plot of Trabecular Surface to Volume.
3. Edit Values for Trabecular Bone Turnover
description: Trabecular bone turnover rate by age range
1
2
<
A
Age Range
Trabecular Bone Turnov
Import Data Export Data
B
0.000
0.0102
llll
C
0.274
0.00822
Interpolation Type: | Linear "H
D
1 .000
0.00288
I
Add Column Delete Column
E
5.000
0.00181
Plot
Unit:
F
10.000
0.00132
Save
G
15.000
o.ooosse
a
Cancel
Figure 50: Values for trabecular bone turnover rate by age. Data are plotted on Figure 51.
Figure
51
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45
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25.000 30.000
Age Range
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.
4. Edit Values for Transfer from Cortical Surface to Blood
Description: Transfer rate from the cortical surface to blood by a Interpolation Type: | Linear
Unit:
it: /day
1
2
A
Age Range
Transfer from Cortical S
B
0.000
0.65
c
0.274
0.65
D
1.000
0.65
<
E
5.000
0.65
F
10.000
0.65
G
15.000
0.65
E
Import Data Export Data
Add Column Delete Column
Plot
Save Cancel
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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46
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J1653
§0.633
mO .613
o
-------
.653
-gO .633
a
m
00.613
m
|o.593
CO
^0.573
3
(Li
-§0.553
§0.533
•4=
|o.513
i
Trabecular Surface to Blood
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
60.00
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 [l-(transfer to blood)]. The default values are 0.35 for the younger
ages (0-15 years), then 0.5 for the older ages.
6. Edit Values for Cortical Surface to Volume Transfer
Description: Fraction transfer from the cortical bone surface to th
1
2
u
A
Age Range
Cortical Surface to Vol
ImportData E xport D ata
| B | C
0.000 0.274
J 0.35 0.35
Add Column Delete Cok
Interpolation Type: Linear
D | E
1 .000 1 5. 000
0.35 0.35
I
jmn Plot
LJ
_;J Unit:
F | G
10.000 15.000
0.35 0.35
a
Save Cancel
Figure 56. Window for editing the value for transfer from cortical surface to volume. Data
are plotted on Figure 57.
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Cortical Surface to Volume
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
60.00!
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.
7. Edit Values for Tiabkular Surface to Volume Transfer
description:
1
2
-------
0.000 5.000 10.000 15.000
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).
I. Edit Values for Total Transfer from Exchange Bone Volume
Description: I Total transfer rate from exchange bone volume by a Interpolation Type: [index
Unit:
it: I /day
1
2
-------
9. Edit Values for Transfer from Exchange to Non-exchange Volume
Description: 1 Fraction transfer from exchange volume to non-exch
1
2
-------
12. Edit Values for Transfer from Bladder to Urine
D escription: T ransfer rate from uninary bladder to urinary tract by I nterpolation Type: | Linear
U nit:
it: /day
1
2
Import Data Export Data Add Column Delete Column
Plot
Save
Cancel
Figure 62: Window for editing the values for the transfer of lead from the bladder to
urine. Data are plotted on Figure 63.
Bladder to Urine Transfer
15.233
14^233
1^33
-------
1 3. Edit Values for Transfer from Liver 2
Description: I Transfer rates from liver section 2 by age range
Interpolation Type: | Linear
1
2
<]
A
Age Range
Transfer from Liver 2
B
0.000
0.00693
Illl
c
0.274
0.00693
D
1.000
0.00693
E
5.000
0.00693
F
10.000
0.0019
G
15.000
0.0019
>J
Import Data Export Data Add Column Delete Column
Plot
Save
Cancel
Figure 64. Age-related coefficients for transfer of lead from Liver2. Data are plotted on
Figure 65.
0.007
0.007
„ 0.006
5-
33 0.006
£ 0.005
UJ
^ 0.005
£ 0.004-
f! 0.004
c
,± 0.003
0.003-
0.002-
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
60.01
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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14. Edit Values foi Tiansfei from Kidney 2
Description: I Transfer rate to kidney section 2 by age range
Interpolation Type: Linear
Unit:
lit: I /day
1
2
A
Age Range
Transfer from Kidney 2
B
0.000
0.00693
c
0.274
0.00693
D
1.000
0.00693
Plot |
Save
Cancel
Import Data Export Data Add Column | Delete Column!
Figure 66: Drop down window for editing the default values for the transfer of lead from
the kidney. Data are plotted on Figure 67.
000 5.000 10.000 15.000
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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31. Edit Values for Depostion Fraction in Fast Soft Tissue
Description: Depostion fraction of lead in fast turnover soft tissue Interpolation Type: | Linear •*• |
Unit:
1
2
-------
32. Edit
Values for Depostion Fraction in
Intermediate Soft Tissue
Description: JDepostion fraction of lead in intermediate turnover s
1
2
0.006
I" 0.005
•t-
—
-r
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
60.00
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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33. Edit Values foi Depostion Fraction in Slow Soft Tissue
Description: Depostion fraction of lead in slow turnover soft tissu Interpolation Type: | Linear
Unit:
1
2
A
Age Range
Depostion Fraction in SI
B
0.000
0.001
c
0.274
0.001
D
1.000
0.001
E
5.000
0.001
F
10.000
0.001
G
15.000
0.001
< >
Plot |
Save
Cancel
Import Data Export Data Add Column | Delete Column!
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 half-
time of two years (Figure 74) (Leggett, 1993).
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Description
1 A
2 C
<]
lrnportD(
Depostion fraction of lead in the brain by age range Interpolation Type: | Linear
A
ge Range
B
0.000 I
epostion Fraction in Br 0.00045 (
sta Export Data
Illl
Add Colum
C D E
1274 1.000 5.000
100045 |o.00045 |o.00015
I
n Delete Column Plot
_;J Unit: |
F G
10.000 15.000
0.00015 1 0.0001 5
S
Save Cancel
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.
23. Edit
Values for Deposition Fraction in Bone
Description: Deposition fraction in bone by age range Interpolation Type: | Linear
1
2
-------
1 d2. Edit Biokinetic Parameters |Xj
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
Parameters
Trabecular Bone Deposition Fraction
Deposition Fraction in Liver 1
Depostion Fraction from Liver 1 to Liver 2
Depostion Fraction from Liver to Small Intestine
Depostion Fraction from Liver to Plasma
Depostion Fraction in Kidney 1
Depostion Fraction in Kidney 2
Depostion Fraction in Fast Soft Tissue
Depostion Fraction in Intermediate Soft Tissue
Depostion Fraction in Slow Soft Tissue
Depostion Fraction in Brain
Depostion Fraction in RBC
Deposition Fraction in EVF
Size of EVF Relative to Plasma
Transfer Rate from Plasma
Deposition Fraction for Plasma Proteins
Rate of Loss For Plasma Proteins
Transfer Rate From RBC
RBC Reference Volume
Plasma Reference Volume
Amount of Blood
Chelation Factor 1
Chelation Factor 2
Default
Values
Edit
0.04
0.1
0.45
0.45
0.02
0.0002
Edit
Edit
Edit
Edit
0.24
0.5
3
2000
0.0004
0.139
Edit
22
30
Edit
0.4
1243
Units
Descriptions
w 1
Fraction of bone deposition going to trabecular by age range
/day
/day
Deposition fraction in liver section 1
Depostion fraction of lead from liver section 1 to section 2
Depostion fraction of lead from liver to small intestine
Depostion fraction of lead from liver to plasma
Depostion fraction of lead in kidney section 1
Depostion fraction of lead in kidney section 2
Depostion fraction of lead in fast turnover soft tissue by age ranc
Depostion fraction of lead in intermediate turnover soft tissue by t
Depostion fraction of lead in slow turnover soft tissue by age ran
Depostion fraction of lead in the brain by age range
Depostion fraction of lead in red blood cells
Depostion fraction of lead in the EVF
Relative size of EVF to plasma
Transfer rate from plasma
Deposition fraction for plasma proteins
Rate of loss for plasma proteins
/day Plasma transfer rate from RBC by age range
dl
dl
dl
Amount of RBC in reference adult male
Amount of plasma in reference adult male
Amount of blood by age range
Chelation Factor 1
Chelation Factor 2
Save
v]
Cancel |
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.
24. Edit Values for Tiabecular Bone Deposition Fraction
D ascription: I Fraction of bone deposition going to trabecular by a I nterpolation Type: | Linear
U nit:
1
2
<
A
Age Range
Trataecular Bone Deposi
B
0.000
0.2
c
0.274
0.2
D
1.000
0.2
E
5.000
0.222
F
10.000
0.25
G
15.000
0.279
nr
Import Data Export Data
Add Column Delete Column
Plot
Save
Cancel
Figure 79. Age-dependent variable for Trabecular Bone Deposition Fraction. Data are
plotted on Figure 80.
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Trabecular Bone Deposition Fraction
0.214
0.000 5.000 10.000 15.000
-r
25.000 30.000
Age Range
40.000
H
60.00!
Figure 80. Trabecular bone deposition fraction.
0.007
0.007
, 0.006
0.006
0.005
0.005
0.004
0.004
c
£ 0.003-
0.003-
0.002-
\
i
ii • • • • m
1—i — — — "- — —
0.000 5.000 10.000 15.000 25.000 30.000 40.000 60.00
Age Range
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 Liverl 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 often 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 Liverl 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).
31 . Edit
Values for Depostion Fraction in
Fast Soft Tissue
Description: JDepostion fraction of lead in fast turnover soft tissue
1
2
< |
A
Age Range
Depostion Fraction in Fa
Import Data
Export Data
B
0.000
0.08345
III!
C
0.274
0.08345 (
Add Column
Delete Colur
Interpolation Type: | Linear _^J
D E
.000 5.000 10.000
3.08345 0.08375 0.0837
I
tin Plot Save
Unit:p
F G
15.000
5 0.08375
s
Cancel
Figure 82. Age-dependent variable for Diffusible Plasma to Fast Soft Tissue. Data are
plotted on Figure 83.
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Deposition Fraction in Fast Soft Tissue
U.UB9
-------
=§ 0.007
OQ
£ 0.006-
1 0.006
o
£ 0.005 -
\
\
"T "
\
\
\
\
• i
t •
, 1
c, |_ . . . .
0.000 5.000 10.000 15.000 25.000 30.000 40.000 60.00
Age Range
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.
33. Edit
Values for Depostion Fraction in
Slow Soft Tissue
Description: JDepostion fraction of lead in slow turnover soft tissu
1
2
-------
25.000 30.000
Age Range
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.
34. Edit Values for Depostion Fraction in Brain
Description: IDepostion fraction of lead in the brain by age range
A
1 Age Range
2 Depostion Fraction in Br
-------
0.000
0.000
0.000
0.000
0.000
0.000
0.000-
Deposition Fraction in Diffusible Plasma to Brain
1—1—
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
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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41 Edit Values for Transfei
Description
1 A
2 T
<]
Import D<
Rate From RBC
a
: Plasma transfer rate from RBC by age range Interpolation Type: | Linear _^J Unit: I /day
A
ge Range
ransfer Rate From RB
jta Export Data
BCD
0.000 0.274 1 .000
0.462 0.462 0.462
Illl |
Add Column Delete Column
E F G
5.000 10.000 15.000
0.277 0.139 0.139
®
Plot Save. | Cancel
Figure 90. Age-dependent variable for the Transfer Rate from RBC. Data are plotted on
Figure 91.
ransfer Rate for Red Blood Cell Paramet
CD
Ct
0.47
0.42
0.37
0.32
I °-27
0.22
0.17
0.000 5.000 10.000 15.000
25.000 30.000
Age Range
40.000
60.00
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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44, Edit Values for Amount of Blood
Description
1 fi
2 A
-------
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.
Pb in System - C:\Piogiam Files VAALMVFiist Flight.mob
81
61
51.646
200.00600.00 1100.00 1700.00 2300.00 2800.00 3400.00 4000.00 4600.00
Age (Days)
43.264100.00
69.16200.00
88.594 300.00
91.215400.00
92.668 500.00
95.866 600.00
99.63 700.00
103.595800.00
107.67900.00
111.8551000.00
116.1781100.00
120.6771200.00
125.391300.00
130.3621400.00
120.521500.00
117.3821600.00
118.8481700.00
121.9121800.00
123.5881900.00
Print
Edit Chart
Close
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 jig Pb/g to 2000 jig Pb/g. Click OK and run the
model as before. You should get:
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Pb in System -t:\Piogiam Files\AALMVFiist Flight mob
192.421
137.421
182.421
156.346100.00
176.329200.00
150.876300.00
131.891 400.00
120.642500.00
116.793600.00
116.086700.00
116.922800.00
118.667900.00
121.0491000.00
123.9461100.00
127.2971200.00
131.0791300.00
135.2871400.00
124.8151500.00
121.1541600.00
122.1831700.00
124.881 1800.00
126.2161900.00
172.421
167.421 -
162.421
100.00500.00 1000.00 1600.00 2200.00 2700.00 3300.00 3900.00 4500.00
Age (Days)
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 jiPb 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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Pb in System - C:\Program Files \AALM\Demo2.mob
100.003000.00 6400.00 9800.00 13500.00 17500.00 21500.00 25500.00 29500.00
Age (Days)
Print
T 3D
Edit Chart
Close
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
Leggett, R.W. (1992b) A generic age-specific biokinetic model for calcium-like elements Radiat. Prot.
Dosim. 41: 183-198.
Leggett, R.W. (1993a) An age-specific kinetic model of lead metabolism in humans. Environ. Health
Perspect. 101: 598-615.
Mickle, M.H. (1998) Structure, use, and validation of the IEUBK model. Environ. Health Perspect. Suppl.
106:1531-1534.
Mushak, P. (1991) Gastro-intestinal absorption of lead in children and adults: overview of biological and
biophysico-chemical aspects. Chem. Speciat. Bioavail. 3: 87-104.
O'Flaherty, E.J. (1998) Physiologically based kinetic model for lead in children and adults. Environ.
Health Perspect. Suppl. 106: 1495-1503.
O'Flaherty, E.J.; Inskip, M.J.; Franklin, C.A.; Durbin, P.W.; Manton, W.I.; Baccanale, C.L. (1998)
Evaluation and modification of a physiologically based model of lead kinetics using data from a
sequential isotope study in Cynomolgus monkeys. Toxicol. Appl. Pharmacol. 149: 1-16.
Oreskes, N. (1998) Evaluation (Not Validation) of Quantitative Models. Environ. Health Perspect.
106(Suppl6): 1453-1460.
Pounds, J.G.; Leggett, R.W. (1998) The ICRP age-specific biokinetic model for lead: validations,
empirical comparisons, and explorations. Environ. Health Perspect. Suppl. 106: 1505-1511.
U.S. EPA (1994a) Guidance Manual for the Integrated Exposure Uptake Biokinetic Model for Lead in
Children. U.S. Environmental Protection Agency. EPA/540/R-93/081, PB93-963510.
U.S. EPA (1994b) Technical Support Document: Parameters and Equations Used in Integrated Exposure
Uptake Biokinetic Model for Lead in Children (v0.99d). U.S. Environmental Protection Agency
EPA/540/R-94/040, PB94-963505.
White, P.O.; Van Leeuwen, P.; Davis, B.D.; Maddaloni, M.; Hogan, K.A.; Marcus, A.H.; Elias, RW.
(1998) The conceptual structure of the integrated exposure uptake biokinetic model for lead in
children. Environ. Health Perspect. 106(Suppl 6): 1513-1530.
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