title: The O'Flaherty model of lead kinetics: an evaluation using data from a lead smelter population.
abstract: The O'Flaherty model of lead kinetics is a physiologically based computer model of lead disposition in humans. The model is based on an age-dependent approach to human growth, with particular attention devoted to bone metabolism. As such, model output is well suited for comparison with noninvasive bone 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. Simulated bone lead and blood lead output were compared with observation, enabling 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 release 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 accord with observed levels in the calcaneus. Model results from the smelter population are consistent with the hypothesis that a polymorphism in the delta-aminolevulinate dehydratase enzyme modifies the kinetics of lead in humans. Further refinements are suggested, which may enhance the ability of the model to explain the underlying relationships between lead exposure and the distribution of lead in the body.
authors.affiliation: Department of Biomedical Technologies, University of Vermont, Burlington, Vermont, 05405-0068, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Fleming
authors.forename: D R
authors.initials: DR
authors.lastname: Chettle
authors.forename: C E
authors.initials: CE
authors.lastname: Webber
authors.forename: E J
authors.initials: EJ
authors.lastname: O'Flaherty
mesh_terms: D000375:Aging / Q000378:metabolism; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D002111:Calcaneus / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007854:Lead / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D016273:Occupational Exposure; D011110:Polymorphism, Genetic / Q000235:genetics; D000623:Porphobilinogen Synthase / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013052:Spectrometry, X-Ray Emission; D013977:Tibia / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014896:Welding
chemical_list: D007854:Lead; D000623:Porphobilinogen Synthase