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Adults and children differ in their susceptibility to the toxic effects of lead. Lead was therefore used as a case study to evaluate intraspecies differences by comparing the adult and child minimal Lowest Observed Adverse Effect Level (LOAEL) or the No Observed Adverse Effect Level (NOAEL), allowing an evaluation of the ten-fold intraspecies uncertainty factor (UF). The lead intakes (in µg/kg/d) necessary to achieve target blood lead (PbB) levels reflecting the minimal LOAEL or NOAEL were determined using biokinetic slope factors (BKSFs), which relate lead uptake to PbB levels. The analyses assumed chronic, low-level oral exposure to lead, and the response of a typical adult and child. Child analyses used a target geometric mean (GM) PbB of 4.6 µg/dL (95% of population

Observed blood lead levels for young children from several communities are compared with blood lead levels predicted for those communities using the USEPA's Integrated Exposure Uptake Biokinetic (IEUBK) Model. In contrast to the compari sons described elsewhere, the blood lead levels observed in the communities con sidered here are not well represented by the model's predictions. The model's predictions for Midvale, UT; Sandy, UT; Cincinnati, OH; and a recent data set for Palmerton, PA, show considerable deviation from observation both for the geometric mean blood lead level and the percent of blood lead levels above 10 µg/dL. Various adjustments in the model to consider play area soils, site specific geometric standard deviations and the time children spend away from their homes do not substantially improve the comparisons to observation. It is difficult to predict a priori the data sets for which the model will yield adequate predictions. This reduces the value of the model for use in communities where ...

This presentation describes the development of a prototype Monte Carlo module for the physiologically-based pharmacokinetic (PBPK) model for lead, created by Dr Ellen O'Flaherty. The module uses distributions for the following: exposure parameters (soil and dust concentrations, daily soil and ingestion rate, water lead concentration, water ingestion rate, air lead concentration, inhalation rate and dietary lead intake); absoption parameters; and key pharmacokinetic parameters (red blood binding capacity and half saturation concentration). Distributions can be specified as time-invariant or can change with age. Monte Carlo model predicted blood levels were calibrated to empirically measured blood lead levels for children living in Midvale, Utah (a milling/smelting community). The calibrated model was then evaluated using blood lead data from Palmerton, Pennsylvania (a town with a former smelter) and Sandy, Utah, (a town with a former smelter and slag piles). Our initial evaluation using distributions for exposure parameters showed that the model accurately predicted geometric (GM) blood lead levels of Palmerton and Sandy and slightly over predicted the GSD. Consideration of uncertainty in red blood cell parameters substantially inflated the GM. Future model development needs to address the correlation among parameters and the use of parameters for long-term exposure derived from short-term studies.