The O'Flaherty model of lead kinetics: An evaluation using data from a lead smelter population

The O'Flaherty model of lead kinetics is a physiologically based computer m odel of lead disposition in humans. The model is based on an age-dependent approach to human growth, with particular attention devoted to bone metabol ism. As such, model output is well suited for comparison with noninvasive b one lead measurements made via X-ray fluorescence. A subset of workers from a lead smelter population were selected for an initial evaluation of the O 'Flaherty model. Detailed blood lead records were used to define input, Sim ulated bone lead and blood lead output were compared with observation, enab ling a refinement of model parameters. A revised version of the O'Flaherty model was then evaluated for the smelter population as a whole. Previously observed trends for the accumulation of lead in cortical bone and the relea se of lead from bone stores were well explained by the revised model, Model predictions for the accumulation of lead in trabecular bone were not in ac cord with observed levels in the calcaneus, Model results from the smelter population are consistent with the hypothesis that a polymorphism in the de lta-aminolevulinate dehydratase enzyme modifies the kinetics of lead in hum ans. Further refinements are suggested, which may enhance the ability of th e model to explain the underlying relationships between lead exposure and t he distribution of lead in the body. (C) 1999 Academic Press.