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.

Using sparse dose-response data for wildlife risk assessment.

Hazard quotients based on a point-estimate comparison of exposure to a toxicity reference value (TRV) are commonly used to characterize risks for wildlife. Quotients may be appropriate for screening-level assessments but should be avoided in detailed assessments, because they provide little insight regarding the likely magnitude of effects and associated uncertainty. To better characterize risks to wildlife and support more informed decision making, practitioners should make full use of available dose-response data. First, relevant studies should be compiled and data extracted. Data extractions are not trivial--practitioners must evaluate the potential use of each study or its components, extract numerous variables, and in some cases, calculate variables of interest. Second, plots should be used to thoroughly explore the data, especially in the range of doses relevant to a given risk assessment. Plots should be used to understand variation in dose-response among studies, species, and other factors. Finally, quantitative dose-response models should be considered if they are likely to provide an improved basis for decision making. The most common dose-response models are simple models for data from a particular study for a particular species, using generalized linear models or other models appropriate for a given endpoint. Although simple models work well in some instances, they generally do not reflect the full breadth of information in a dose-response data set, because they apply only for particular studies, species, and endpoints. More advanced models are available that explicitly account for variation among studies and species, or that standardize multiple endpoints to a common response variable. Application of these models may be useful in some cases when data are abundant, but there are challenges to implementing and interpreting such models when data are sparse.

Lead toxicity, vulnerable subpopulations and emergency preparedness.

This paper reviews some evidence of the toxic effects of lead (Pb) in the context of vulnerable subpopulations and emergency preparedness. Pb is ubiquitous in the environment and is used in many building materials. Environmental Pb concentrations and body burdens of Pb have been shown to increase following disasters. Pb is a systemic toxicant with no known beneficial biological function and, for several endpoints, no identified threshold of toxicity. The fetus, children, pregnant and elderly are particularly susceptible to some of the toxic effects of Pb. Pb exposures in infancy have been shown in vivo to produce an equal degree of neurobehavioural impairment as exposures of much longer duration at equivalent doses during adolescence. Evidence from animal bioassays indicates that the carcinogenic potency of perinatal Pb exposure may be about 3-fold higher than adult lifetime exposure at an equivalent dose. Animal assays show up to a 12-fold difference between fetal, neonatal and adult life stages in sensitivity to the immunological effects of Pb. Pb exposure is associated with increased risk of cardiovascular and cerebrovascular morbidity and mortality--health endpoints for which the elderly are at increased risk. Finally, endogenous and exogenous variables, such as psychological and physiological stress, dietary deficiencies and concomitant exposure to other chemical, biological and radiological hazards, can also potentially modify or potentiate the toxic effects of Pb. Because of the potential for concurrent influence of these modifying variables in a post-disaster environment, emergency response planners are encouraged to consider disaster victims and responders, as a whole, as a potentially vulnerable subpopulation.