1. The Use of the Integrated Exposure Uptake and Biokinetic Model as a Predictive Tool for Lead Based Paint Risk Assessments Richard Troast, PhD Principal, Troast Environmental Consulting LLC

2. Thanks and Acknowledgements
Dr Gary Diamond Syracuse Research Corp
Dr Mark Follansbee Syracuse Research Corp
Dr Mark Maddaloni US EPA Reg II, New York City

3. WHAT IS THE IEUBK MODEL?
The IEUBK model is the most commonly used physiologically based pharmacokinetic (PBPK) model for Pb in children.
The Model for is used to predict the risk of elevated blood
lead (PbB) levels in children (under the age of seven) that are
exposed to specific environmental lead (Pb) sources.
The model predictions of the risk (e.g., probability) for the typical
child, exposed to specified Pb concentrations, will have
a PbB level greater or equal to the level associated with adverse health effects (10 ug/dL)

4. What is a Biokinetic Model?
Biokinetic models assess the routes of environmental exposure to a substance and determine the distribution of this substance among the various body tissues in humans.
Biokinetic models work best when there is a known effect that is associated with a specific tissue concentration in humans. –e.g., neurological impairment in children

5. The Benefits of a Lead Biokinetic Model
Lead Risk Assessment is Different
In comparison to most other environmental contaminants, the degree of uncertainty about the health effects of lead is quite low.
Some of these effects, particularly changes in the levels of certain blood
enzymes and in aspects of children's neurobehavioral development, may occur at blood lead levels so low as to be essentially without a threshold.
EPA decided that it was inappropriate to derive a Reference Dose (RfD) for lead developed a procedure to regulate lead exposure by using a biomarker (blood lead concentration).
Environmental exposures to lead are modeled to predict blood lead levels associated with those exposures.

6. IEUBK Model Background
The IEUBK model is the primary tool used in determining risk-based cleanup levels at Pb contaminated sites.
The following modules are utilized in predicting PbB concentrations, and risks in the IEUBK model:
Exposure,
Uptake,
Biokinetic,
Probability Distribution.

7. IEUBK INPUT DATA MODULES
Exposure Module. This module uses Pb concentrations in the
environment and the rate at which a child breathes or ingests
contaminated media to determine Pb exposure.
Uptake Module. This module modifies the Pb intake rates
calculated by the Exposure Module using absorption factors to
predict the uptake of Pb from the lungs and GI tract

8. IEUBK INPUT DATA MODULES
Biokinetic Module. This module addresses the transfer of absorbed
Pb between blood and other body tissues; the elimination of Pb from the body. The total amount of Pb in each body compartment is age dependent and calculated using total Pb uptake derived by the Uptake Module.
Probability Distribution Module. This module estimates a
plausible distribution of PbB concentrations that is centered on the
geometric mean PbB concentration calculated by the Biokinetic
Module

9. Plasma extra-cellular fluid
Structure of the IEUBK Model for Lead in Children*
Exposure Compartment
Air
Diet
Water
Dust
Other
Soil
Respiratory
Tract
Gastrointestinal tract
Gastrointestinal tract
Respiratory Tract
Gastrointestinal tract
Feces
Plasma extra-cellular fluid
Biokinetic Compartment
Plasma extra-cellular fluid
Feces
Trabecular Bone
Cortical bone
Kidney
Red blood cells
Liver
Other soft
tissues
Urine
Skin, hair, nails

10. Comparison of Selected IEUBK Calibration Data vs Observed PbB

11. IEUBK History

12. IEUBK Validation Evaluation and Validation of the IEUBK
IV&V evaluated the following:
1. Scientific underpinnings of the model structure
2. Adequacy of parameter estimates
3. Mathematical relationships (as computer code)
4. Empirical comparisons (predicted vs. observed)
The process and results of the IEUBK validation are available online (TRW web site)
1994 Validation Strategy for the IEUBK
1998 Empirical Comparisons Manuscript (Hogan et al., 1998)

13. What are the limitations of the IEUBK model?
The IEUBK model should not be relied upon to predict PbB accurately above 30 ug/dL.
The IEUBK performs it’s statistical probability optimally when the exposure periods are in excess of 90 days. Higher variability can be expected at shorter exposure periods especially where exposure periods are irregular in duration or frequency.
The IEUBK model wasn’t designed as a tool for a specific child but instead designed to predict a probability of a child’s elevated lead risk based upon a specific exposure scenario

14. How can this be used for lead based residential settings
If the measured blood lead (PbB) is >30 the IEUBK inputs will not preform adequately.
If the residential setting is highly mobile then the IEUBK will not perform adequately
The IEUBK can not with statistical certainty predict an individual’s PbB.
It can use simulated exposure conditions and the predicted PbB could then be used as a correlation to blood lead reports.
It can be used to simulate exposure variables (i.e. indoor or outdoor exposures)
The findings or predicted PbB can be adjusted to reflect current child health guidance

15. How Do I Use the IEUBK Step 1 Download the IEUBK ( http://www. epa
How Do I Use the IEUBK Step 1 Download the IEUBK ( Step 2 Download the Users Guide (

16. IEUBK Beginner and Advanced Modes of Operation
Users have the option of running the IEUBK in Beginner or Advanced Mode.
The advanced mode is similar to the operation of previous versions.
The Beginner mode guides new users through data entry using a wizard.
This option may be disabled by checking the box “Always start in Advanced User Mode”

29. IEUBK Input data Air Standard Water Standard Diet Standard
Dust Based on Pb in soil
Maternal Standard
Alternate If Pb Paint is present (ug/day) Need to estimate from XRF data

30. Pb Paint Conversion

31. SIGNIFICAN EVENTS USED IN STUDY
Significant Events
comments
life day
PbB
event
birth
house 1
1632 1
est.
370 12
Initial PbB
538
move
house 2
415
667
house 3
803
868
house 4
1504
896 32
927 31
990 37
1040
1061
31.5
1158
house 5
1620
1260 29
1341
10 bckgrd
house 6
502
IEUBK est
1421 30
house 7
no move date
1545
house 8
IEUBK est
1602 nr
house 9
6732
1739 11
1765
house 10
1818
2006
house 11
2302 22 ??
house 12
3106
house 13
Howard County

32. Mr C PbB in residences MEASURED AND ESTIMATED

34. Other Lead Models

35. the original set of data.
Observations These are the values for blood leads (PBB) as provided with
the original set of data.
House 1-4 represent the listed residences for Mr X from the PbB reports
AGE MO
HOUSE
PBB 24 1 44 25 26 33 28 21 32 34 2 37 3 16 40 12 43 10 52 4 7 58 6
Observations These are the values for blood leads (PBB) as provided to me with the original set of data. House 1-4 represent the listed residences for Mr X from the PBB reports

36. This is a simple exponential model fit that was based upon the observed blood lead. A single elimination half-time of lead kinetics accounts for most of the variability in blood lead and shows the expected decline. The color codes represent the residences of Mr. X -H1 (red), H2 (blk), H3 (red), H4 (blk).

37. Exponential model extended to origin.

38. The ICRP model predictions in which all lead exposure above background is assigned to H1. This is an assumption based on the blood lead data and which fits the curves in the previous slides. The dotted line shows a background exposure in DC that yields a quasi-steady state blood lead of approximately 5 μg/dL. The solid line represents a continuous exposure at H1 (plus background), beginning at age-day 400 and extending to age-day 990 (approximate day of move to H2). The H1 simulation yields a quasi-steady state blood lead concentration that approximates the mean blood lead concentration observed at H1 (shown is the mean ± 2SD). Although many different scenarios could yield a similar degree of agreement with the observations, the simplest scenario attributes all above background exposure to H1, and no above background exposures H2, H3, or H4. Therefore, exposures at H2, H3, and H4 are not needed to explain the observed pattern of decrease in blood lead concentration. In short, this slide demonstrates that by the time Mr. X resided in residence 4 ( Eldon Place), he was not exposed to lead above background levels within 2 SDs based on the reported PBBs. In fact, the data strongly suggest that there was an incident occurring early in Mr. Jones life during the time he resided at the first residence which caused the PBB to spike, and that after this spike to 44ug/dl whatever caused this elevation was removed and further exposure was minimized. One could also speculate that PBB’s reported at the other residences were as a result of the original lead exposure. If there were continuing exposures to lead at residence 2 and 3 the decline noted from the models would not fit the expected curves shown in slides 2 and 3.

39. Association between average blood lead concentration and average IQ decrement expected in a population of similarly exposed children. The plot shows a log-linear relationship in the blood lead range 1-40 μg/dL (from Lanphear et al. 2005), with a linear extrapolation from 1 to 0 μg/dL. If we assume that Mr. J was born with an average intelligence level, the most recent data I could find suggested a range of IQ, then Mr. J reported IQ levels of fit the curve shown above within 2SDs. Mr. J highest PbB was 44 which is associated with an IQ decrement of 13 points. The simple mathematics suggest that Mr. J should have an IQ of 82 after the exposure peak of 44ug/dl. We do not know what his baseline IQ was so if we apply 2 SDs to this curve we fit Mr. J reported IQs to these results.

40. Could the IEUBK be used for the previous example