Physiologically based modeling of lead kinetics: a pilot study using data from a Canadian population.

The Canadian population is currently subject to low, chronic lead exposure and an understanding of its effects is of great significance to the population's health. Such low exposure is difficult to measure directly; approximation by physiologically based modeling may provide a preferable approach to population analysis. The O'Flaherty model of lead kinetics is based on an age-dependent approach to human growth and development and devotes special attention to bone turnover rates. Because lead is a bone-seeking element, the model was deemed ideal for such an analysis. Sample from 263 individuals of various ages from the Greater Toronto Area were selected to evaluate the applicability of the current version of the O'Flaherty model to populations with low lead exposure. For each individual, the input value of lead exposure was calibrated to match the output value of cortical bone lead to the individual's measured tibia lead concentration; the outputs for trabecular bone, blood, and plasma lead concentrations obtained from these calibrations were then compared with the subjects' measured calcaneus, blood, and serum lead concentrations, respectively. This indicated a need for revision of the model parameters; those for lead binding in blood and lead clearance from blood to bone were adjusted and new outputs were obtained in the same fashion as before. Model predictions of trabecular lead concentration did not agree with measurements in the calcaneus. The outputs for blood and plasma lead concentrations were highly scattered and, on an individual level, inconsistent with corresponding measurements; however, the general trends of the outputs matched those of the measurements reasonably well, which indicates that the revised blood lead binding and lead clearance parameters may be useful in future studies. Overall, the analysis showed that with the revisions to the model discussed here, the model should be a useful tool in the analysis of human lead kinetics and body burden in populations characterized by low, chronic exposure to lead from the general environment.

Factors influencing uncertainties of in vivo bone lead measurement using a (109)Cd K X-ray fluorescence clover leaf geometry detector system.

A (109)Cd K X-ray fluorescence (KXRF) measurement system consisting of four detectors in clover-leaf geometry is a non-invasive, low-radiation-dose method of measuring bone lead concentration. Its high precision in estimating the bone lead content makes it a promising tool for the determination of the low levels of lead currently found in the general population. After developing the clover-leaf geometry system, the system was used for the first time in a major survey in 2008 to measure the lead levels of 497 smelter employees (an occupationally exposed group with high lead levels). Since the delivered effective dose of the bone lead system in clover-leaf geometry is small (on the order of nSv), the technique can be used to measure the bone lead of sensitive populations such as the elderly and children. This detector system was used from 2009 to 2011, in a pilot study that measured the bone lead concentration of 263 environmentally exposed individuals (termed the EG group) residing in Toronto, Ontario, Canada. In this paper, the factors that influence uncertainties in lead content in tibia (cortical bone) and calcaneus (trabecular bone) are discussed based on gender, age, and body mass index (BMI) by using analysis of variance (ANOVA) and multiple linear regression models. Results from the two study groups (the EG group versus the occupationally exposed smelter employees) are compared where appropriate (i.e. for males older than 20). Results from univariate analyses showed that females have higher tibia uncertainty compared to males. We observed significant differences for both calcaneus and tibia uncertainty measures (p < 0.0005) among different age groups, where the uncertainties were highest in the lowest age group (<11 years). Lastly, and perhaps most significantly, we found that the product of source activity and measurement time influenced the precision of measurements greatly, and that this factor alone could account for the higher uncertainties observed for the male cohort of the EG group versus the smelter employees.

The estimation of the rates of lead exchange between body compartments of smelter employees.

The overwhelming proportion of the mass of lead (Pb) is stored in bone and the residence time of Pb in bone is much longer than that in other tissues. Hence, in a metabolic model that we used to solve the differential equations governing the transfer of lead between body compartments, three main compartments are involved: blood (as a transfer compartment), cortical bone (tibia), and trabecular bone (calcaneus). There is a bidirectional connection between blood and the other two compartments. A grid search chi-squared minimization method was used to estimate the initial values of lead transfer rate values from tibia (λTB) and calcaneus (λCB) to blood of 209 smelter employees whose bone lead measurements are available from 1994, 1999, and 2008, and their blood lead level from 1967 onwards (depending on exposure history from once per month to once per year), and then the initial values of kinematic parameters were used to develop multivariate models in order to express λTB and λCB as a function of employment time, age, body lead contents and their interaction. We observed a significant decrease in the transfer rate of lead from bone to blood with increasing body lead contents. The model was tested by calculating the bone lead concentration in 1999 and 2008, and by comparing those values with the measured ones. A good agreement was found between the calculated and measured tibia/calcaneus lead values. Also, we found that the transfer rate of lead from tibia to blood can be expressed solely as a function of cumulative blood lead index.

Nonlinearity in the relationship between bone lead concentrations and CBLI for lead smelter employees.

494 smelter employees from New Brunswick participated in a bone lead survey conducted by McMaster University in 2008, using the four element "clover-leaf" geometry germanium detector system. The employees were measured at two different bone sites, tibia and calcaneus, each measurement lasting 30 minutes. Scattered photons, including Pb X-rays, were collected by the germanium detectors located behind the ¹°9Cd source. A strong positive correlation was observed between tibia and calcaneus lead concentrations. Having been provided with blood lead levels, a cumulative blood lead index (CBLI) was generated. The employees were classified into four groups based on their date of hire, and their CBLI levels were compared to their tibia and calcaneus lead concentrations in the different groups. The slopes of bone Pb versus CBLI varied amongst groups, with those hired earliest showing the steepest slopes. This could be taken to imply a non-linearity in the uptake of Pb by bone from blood. In this paper, the association of the bone lead concentrations versus CBLI has been expressed by a polynomial function for the whole group of employees.

In vivo measurement of lead in the bones of smelter workers using the four-element 'clover-leaf' geometry detector system.

A total of 497 smelter employees from New Brunswick participated in a bone lead survey conducted by McMaster University in 2008 to examine the efficiency of lead exposure control programmes and a four-element 'clover-leaf' geometry detector system. Nearly 42% of the subjects had participated in both the previous surveys performed in 1994 and 1999. After developing the clover-leaf geometry system in 2006, the reliability of the system based on examining the consistency of four detectors and improving the minimum detection limit (MDL) was tested for the first time in 2008 by measuring lead levels of a large population that was occupationally exposed to lead. The Z test was used to study the distribution of the lead concentration calculated based on K(α) and K(ß) lead x-rays, where the results were broadly consistent with a normal distribution criterion, with relatively small means and standard deviations of between 1 and 2. The MDL of the clover-leaf geometry system was improved on average for tibia and calcaneus by a factor of 3.1 compared to the 1999 and 1994 surveys in which a conventional system (one detector) was used. Furthermore, by comparing the results of the three mentioned surveys, the 2008 results were found to represent the highest precision.