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

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

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)

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

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.

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.

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

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

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  

Comparison of Selected IEUBK Calibration Data vs Observed PbB

IEUBK History

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)

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

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

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 ( http://www.epa.gov/superfund/health/contaminants/lead/products.htm#ieubk) Step 2 Download the Users Guide (http://www.epa.gov/superfund/health/contaminants/lead/products.htm)

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”

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

Pb Paint Conversion  

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

Mr C PbB in residences MEASURED AND ESTIMATED

Other Lead Models

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

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).

Exponential model extended to origin.

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.

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 95-100 IQ, then Mr. J reported IQ levels of 67-70 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.

Could the IEUBK be used for the previous example