In this study, 539 occupationally exposed subjects received in vivo bone lead measurements using 109Cd excited K X-ray fluorescence (109Cd K XRF). Of these subjects, 327 had previously been measured five years earlier. Measurements were made from both tibia and calcaneus samples, taken to reflect cortical and trabecular bone, respectively. Changes in tibia lead concentration related negatively to initial tibia lead concentration and positively to both lead exposure between the measurement dates and initial calcaneus lead concentration. This finding confirmed and strengthened the interpretation of an earlier study involving fewer subjects. With the larger data set it was possible to examine subgroups of subjects. This showed that people aged less than 40 years had a shorter half-life for the release of lead from the tibia (4.9, 95% CI 3.6-7.8 years) than did those older than 40 (13.8, 95% CI 9.7-23.8 years). Similarly, less intensely exposed subjects (lifetime average blood lead < or = 25 micrograms dL-1) had a shorter tibia lead half-life (6.2, 95% CI 4.7-9.0 years) than those with a lifetime average blood lead > 25 micrograms dL-1 (14.7, 95% CI 9.7-29.9 years). Age and measures of lead exposure were strongly correlated; nevertheless, age matched subgroups with high and low intensity exposures showed clearance rates that were significantly different at the 10% level, with the lower exposure intensity again being associated with the faster clearance. These findings imply that current models of human lead metabolism should be examined with a view to adjusting them to account for kinetic rates varying with age and probably also with exposure level.
This paper describes a new metabolic model for lead in humans and a numerical method to solve the differential equations governing the transfer of lead between body compartments. The model includes 3 compartments-cortical bone, trabecular bone and blood-and accounts for absorption from external sources and release through excreta. Estimation of the lead kinetics parameters was performed using the grid search method. Grid search is a simple procedure that allows the fit of an arbitrary function to data. When applied to data from occupationally exposed populations, the method demonstrated the exposure dependence of the rate of lead uptake and release by the compartments in the model. The results confirm and refine previous observations of the significant decrease of the transfer rate of lead from cortical bone to blood with increasing exposure, as expressed by half-lives of (in years): 6.5 +/- 0.7, 13.6 +/- 1.0 and 47.5 +/- 2.3, in subgroups of low, intermediate and high long-term lead exposure. A similar trend was observed for the transfer rate from trabecular bone, which could be statistically supported for the first time. Reduction by a factor of 7 to 10 in the default values assigned to the fractional removal of lead from cortical bone to plasma in existing metabolic models was also predicted. These results can be used in the review of current metabolic models for lead, which are still based on the assumption of a constant rate of lead removal from bone, independently of the level of exposure.
Due to signal attenuation in overlying soft tissue, development of x-ray fluorescence systems to measure low atomic number elements, such as strontium, in human bone required a search for a skeletal site with thin overlying tissue. This paper reports ultrasound measurements of overlying tissue on 10 subjects, at four anatomical sites. The average tissue thickness at the finger was (2.9+/-0.7) mm. The average tissue thicknesses were (3.6+/-0.7) mm, (4.8+/-2.0) mm, and (8.4+/-1.7) mm at forehead, tibia and heel, respectively. Additionally, both parametric and nonparametric approaches to the relationship between body mass index (BMI) and tissue thickness suggest that there is a significant linear correlation between the subject's BMI and overlying tissue at the finger and heel bone. These correlations might be used as a criterion to perform XRF measurements, however a larger data set is required to address these correlations more clearly.
The effect of covariance between the K alpha and K beta lead peak concentrations on the uncertainty in the (109)Cd K x-ray fluorescence measurement of lead in bone is addressed here. It is commonly believed that this covariance arises as a result of the mutual dependence of the ratios of x-ray to coherent amplitudes on the same coherent peak amplitude. Previous work assumes statistical independence between spectral quantities of interest, crudely estimates the uncertainties in the lead peak concentrations, and suggests that the effect of covariance on the measurement uncertainty is small and can be ignored. Consequently, the current method followed by most laboratories reports the measurement uncertainty as if the fluctuations in the measured peak concentrations were independent. The robustness of such assumption, however, is undermined by existing epidemiological data. This paper assesses the magnitude of the covariance effect, using a method based on the observed significant correlations between the ratios of x-ray to coherent peak amplitudes in series of repeat phantom measurements. The revised uncertainties following this approach can exceed the uncertainties estimated by the accepted method by as much as 40%, which suggests a much stronger effect of covariance on the measurement uncertainty than previously reported.
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