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|Title:||Human Lead Metabolism: Chronic Exposure, Bone Lead and Physiological Models|
|Authors:||Fleming, David E.B.|
|Advisor:||Webber, Colin E.|
Chettle, David R.
|Department:||Physics and Astronomy|
|Keywords:||Astrophysics and Astronomy;Astrophysics and Astronomy|
|Abstract:||<p>Exposure to lead is associated with a variety of detrimental health effects. After ingestion or inhalation, lead may be taken up from the bloodstream and retained by bone tissue. X-ray fluorescence was used to make in vivo measurements of bone lead concentration at the tibia calcaneus for 367 active and 14 retired lead smelter workers. Blood lead levels following a labour disruption were used in conjunction with bone lead readings to examine the endogenous release of lead from bone. Relations between bone lead and a cumulative blood lead index differed depending on time of hiring. This suggests that the transfer of lead from blood to bone has changed over time, possibly as a result of varying exposure conditions. A common polymorphism in the δ-aminolevulinate dehydratase (ALAD) enzyme may influence the distribution of lead in humans. Blood lead levels were higher for smelter workers expressing the more rare ALAD² allele. Bone lead concentrations, however, were not significantly different. This implies that a smaller proportion of lead in blood is distributed to tissue for individuals expressing the ALAD² allele. The O'Flaherty physiological model of lead metabolism was modified slightly and tested with input from the personal exposure histories of smelter workers. The model results were consistent with observation in terms of endogenous exposure to lead and accumulation of lead in cortical bone. Modelling the calcaneus as a trabecular bone site did not reproduce observed trends. Variations in lead metabolism between different trabecular sites may therefore be significant. The model does not incorporate a genetic component, and its output did not reflect observed differences in this respect. This result provides further support for the influence of the ALAD polymorphism on lead metabolism. Experimental trials with a digital spectrometer revealed superior energy resolution and count throughput relative to the conventional x-ray fluorescence system. The associated reduction in the uncertainty of lead measurement has the potential to benefit future surveys and modelling efforts.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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