Biokinetic models uptake rates

Any disagreement between biokinetically predicted PbB results and accurate blood lead measurements indicates discordances in input parameters (assuming basic computational soundness). The EPA lEUBK model has a number of input steps where uncertainty and variability can arise. Two are significant (1) the bioavailability or uptake rate of lead from media directly relevant to infants, toddlers, and older children and (2) the amount of lead-contaminated medium ingested. 

The lEUBK model in its intake, uptake, and biokinetic components attempts to take some cognizance of interindividual variability of Pb in children s blood. Overall, this variability derives from both Pb exposure variation across children in a population as well as differences internally (bioki-netically) in the form of differing Pb retention and excretion rates. Comparatively speaking, it is exposure variability that ranges more widely. Pb intake rates and subsequent uptake rates, for example, can differ by orders of magnitude across Pb-contaminated environmental media... 

The Leggett Model simulates lead biokinetics in liver with two compartments the first simulates rapid uptake of lead from plasma and a relatively short removal half-life (days) for transfers to plasma and to the small intestine by biliary secretion a second compartment simulates a more gradual transfer to plasma of approximately 10% of lead uptake in liver. Different transfer rates associated with each compartment are calibrated to reproduce patterns of uptake and retention of lead observed in humans, baboons, and beagles following intravenous injection, as well as blood-to-liver concentration ratios from data on chronically exposed humans. Similarly, the Leggett Model simulates lead biokinetics in three compartments of soft tissues, representing rapid, intermediate, and slow turnover rates (without specific physiologic correlates). 

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