Tibia Lead Concentration Research Articles

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.

Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

BackgroundGlutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1 Val105 and GSTM1 deletion polymorphisms modify the lead-cognitive function association. MethodsWe used repeated measures analysis to compare the association between cumulative lead biomarkers—bone lead measured using K-shell X-Ray Fluorescence—and Mini-Mental State Exam (MMSE) score by GST variants, adjusted for covariates, among Normative Aging Study participants, a Boston-based prospective cohort of men. We had complete data for 698 men (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142 observations) for GSTP1 analyses. ResultsA 15μg/g higher tibia lead concentration (interquartile range of tibia lead) was associated with a 0.24 point decrement in MMSE score among GSTP1 Val105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p=0.01). The association among GSTP1 Val105 carriers was comparable to that of 3 years of age in baseline MMSE scores. The association between tibia lead and MMSE score appeared progressively steeper in participants with increasingly more GSTP1 Val105 alleles. A modest association between tibia lead and lower MMSE score was seen among participants with the GSTM1 deletion polymorphism. Neither of the glutathione S-transferase variants was independently associated with cognitive function, nor with lead biomarker measures. The results pertaining to patella lead were similar to those observed for tibia lead. ConclusionOur results suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.

Cumulative exposure to lead and cognition in persons with Parkinson's disease

Dementia is an important consequence of Parkinson's disease (PD), with few known modifiable risk factors. Cumulative exposure to lead, at levels experienced in the community, may exacerbate PD-related neural dysfunction, resulting in impaired cognition. Among 101 persons with PD ("cases") and, separately, 50 persons without PD ("controls"), we evaluated cumulative lead exposure, gauged by tibia and patella bone lead concentrations, in relation to cognitive function, assessed using a telephone battery developed and validated in a separate sample of PD patients. We also assessed the interaction between lead and case-control status. After multivariable adjustment, higher tibia bone lead concentration among PD cases was associated with worse performance on all of the individual telephone tests. In particular, tibia lead levels corresponded to significantly worse performance on a telephone analog of the Mini-Mental State Examination and tests of working memory and attention. Moreover, higher tibia bone lead concentration was associated with significantly worse global composite score encompassing all the cognitive tests (P = 0.04). The magnitude of association per standard deviation increment in tibia bone lead level was equivalent to the difference in global scores among controls in our study, who were approximately 7 years apart in age. The tibia lead-cognition association was notably stronger within cases than within controls (P(difference) = 0.06). Patella bone lead concentration was not consistently associated with performance on the tests. These data provide evidence suggesting that cumulative exposure to lead may result in worsened cognition among persons with PD.

Relationship between lead exposure, cognitive function, and drug addiction: Pilot study and research agenda

Lead toxicity has been associated with behavioral handicaps, reading disability, antisocial and hyperactive behavior, juvenile delinquency, and impaired cognition. In addition, preclinical studies suggest an association with drug addiction; e.g., animals treated with lead either pre- or postnatally self-administer opiates at a much higher rate than untreated animals. Iron deficiency further increases the risk of lead toxicity through enhanced absorption of lead in the gastrointestinal tract. Female injection drug users have a high prevalence of iron deficiency, although the question remains as to whether this relationship is either a partial function of high lead exposure or heroin use. Specific aims were to preliminarily determine whether female injection heroin users have high tibial lead concentrations, a marker for cumulative lead exposure, compared with normal reference populations, and whether cognitive deficits potentiated the relationship between lead exposure and frequency of heroin use. Tibial lead concentrations were measured via 109Cd-based K-shell X-ray fluorescence. In 26 female injection heroin users, mean (standard deviation (SD)) tibial lead concentration was 14.5 (6.8) μg/(g bone mineral), which was 1.8 times higher than the tibial lead concentration found among age-adjusted normal community-dwelling women. Interaction effects of tibial lead concentration and selected cognitive functions on frequency with which heroin was used were significant. Further research is warranted to determine whether a history of lead exposure is associated with increased proclivity to drug addiction.

Patients Prefer Pictures to Numbers to Express Cardiovascular Benefit From Treatment

This study aimed to determine which methods of expressing a preventive medication's benefit encourage patients with known cardiovascular disease to decide to take the medication and which methods patients prefer. We identified patients in Auckland, New Zealand, family practices located in areas of differing socioeconomic status who had preexisting heart disease (myocardial infarction, angina, or both) and were taking statins. The patients were interviewed about their preference for methods of expressing the benefit of a hypothetical medication. Benefits were expressed numerically (relative risk, absolute risk, number needed to treat, odds ratio, natural frequency) and graphically. Statistical testing was adjusted for practice. We interviewed 100 eligible patients, representing a 53% response rate. No matter how the risk was expressed, the majority of patients indicated they would be encouraged to take the medication. Two-thirds (68) of the patients preferred 1 method of expressing benefit over others. Of this group, 57% preferred the information presented graphically. This value was significantly greater (P <.001) than the 19% who chose the next most preferred option, relative risk. Few patients preferred absolute risk (13%) or natural frequencies (9%). Only a single patient (1%) preferred the odds ratio. None preferred number needed to treat. Ninety percent of patients responding to a question about framing preferred positive framing (description of the benefit of treatment) over negative framing (description of the harm of not being treated). Although number needed to treat is a useful tool for communicating risk and benefit to clinicians, this format was the least likely to encourage patients to take medication. As graphical representation of benefit was the method patients preferred most, consideration should be given to developing visual aids to support shared clinical decision making.

Changes in Systolic Blood Pressure Associated With Lead in Blood and Bone

Several studies have examined longitudinal associations of blood pressure change or hypertension incidence with lead concentration in blood or bone. It is not clear whether the observed associations reflect an immediate response to lead as a consequence of recent dose or rather are a persistent effect of cumulative dose over a lifetime. We followed 575 subjects in a lead-exposed occupational cohort in South Korea between October 1997 and June 2001. We used generalized estimating equation models to evaluate blood pressure change between study visits in relation to tibia lead concentrations at each prior visit and concurrent changes in blood lead. The modeling strategy summarized the longitudinal association of blood pressure with cumulative lead dose or changes in recent lead dose. On average, participants were 41 years old at baseline and had worked 8.5 years in lead-exposed jobs. At baseline, the average +/- standard deviation for blood lead was 31.4 +/- 14.2 microg/dL, and for tibia lead, it was 38.4 +/- 42.9 microg/g bone mineral. Change in systolic blood pressure during the study was associated with concurrent blood lead change, with an average annual increase of 0.9 (95% confidence interval = 0.1 to 1.6) mm Hg for every 10-microg/dL increase in blood lead per year. The findings in this relatively young population of current and former lead workers suggest that systolic blood pressure responds to lead dose through acute pathways in addition to the effects of cumulative injury.

In vivo investigation of a new 109Cd γ-ray induced K-XRF bone lead measurement system

A new 109Cd γ-ray induced K-XRF bone lead measurement system using an array of four detectors has been developed. Previous results from Monte Carlo (MC) simulations and experiments with phantoms predicted that it would be about three times more sensitive than the conventional system, albeit using a more active source. A dosimetry study has been performed for this system and it demonstrated that the dose delivered to the measured individuals is acceptable even for 5-year-old children. Approval to apply this system to human studies has been received from the Research Ethics Board. In this study, 20 adult volunteers, 10 male, 10 female, were recruited to have their tibia measured with both the conventional system and the new system. The result confirmed the improvement predicted by the MC simulations and the in vitro measurements. Two other interesting points were discovered from the data. One is that the data from the new system showed a significant positive correlation between age and tibia lead concentration, while the data from the conventional system do not. The other is that 85% of the tibia lead concentrations were under the minimum detection limit when measured by the conventional system, and the proportion reduced to 50% when measured by the new system.

Assessment of Lead Exposure Risk in Locksmiths

Exposure to lead has been well recognized in a number of work environments, but little is known about lead exposure associated with machining brass keys containing lead. The brass that is widely used for key manufacturing usually contains 1.5% - 2.5 % of lead. Six (6) licensed locksmiths and 6 case-matched controls successfully completed the pilot study to assess the prevalence of increased body lead burden of professional locksmiths. We measured both Blood Lead (atomic absorption spectrometry), bone-lead (KXRF) and had each subject complete a health and lead exposure risk questionnaire. One locksmith had not cut keys during the past two years, therefore this subject and case-matched control was excluded from the blood lead analysis only. The average blood-lead concentration (+/-SEM) for the 5 paired subjects was 3.1 (+/- 0.4) microg/dL and 2.2 (+/- 0.3) microg/dL for controls. Bone measurements, including all 6 paired subjects, showed tibia lead concentration (+/-SEM) for locksmiths and controls was 27.8 (+/- 2.3) microg/g and 13.7 (+/- 3.3) microg/g, respectively; average calcaneus lead concentration for locksmiths and controls was 31.9 (+/- 3.7) microg/g and 22.6 (+/- 4.1) microg/g, respectively: The t-test shows a significantly higher tibia lead (p<0.05) and blood lead (p<0.05) for locksmiths than for their matched controls, but no significant difference for calcaneus lead (p>0.10). Given that the mean tibia bone lead concentration was 13.1 microg/g higher in locksmiths than in their matched controls, this average difference in the two groups would translate to an OR of increased hypertension in locksmiths of between 1.1 and 2.3, based on the published literature. Even with the very small number of subjects participating in this pilot study, we were able to demonstrate that locksmiths had significantly higher current exposure to lead (blood lead concentration) and significantly higher past exposure to lead (tibia lead concentration) than their age, sex and ethnically matched controls. Additional research is needed to fully identify the prevalence and associated risk factors for occupational exposure of lead in this previously understudied profession.

Impact of Occupational Exposure on Lead Levels in Women

In 1994, 207 women participated in a study designed to examine the effects of occupational exposure and various lifestyle factors on bone and blood lead levels. In vivo measurements of Pb concentrations in tibia were performed by X-ray fluorescence. All 108 former smelter employees and 99 referents provided blood samples and answered a questionnaire on lifestyle characteristics and the relevant medical history. Lead concentrations in tibia and blood were significantly higher in the exposed group. The difference in mean bone Pb concentrations of the two groups is markedly greater than the difference in the mean blood Pb concentrations, supporting the view that bone Pb measurements are a more reliable determinant of Pb body burden. Chronic exposure did not result in any statistically significant differences in adverse pregnancy outcomes. A significantly lower age at the onset of menopause in occupationally exposed women may suggest that Pb causes adverse changes in the pattern of estrus and menses. The exposed women had lower bone Pb concentrations than those found in most studies on predominantly male workers. Blood Pb concentrations remain increased in women long after the cessation of occupational exposure, reflecting the importance of the endogenous exposure. The endogenous exposure relation found for postmenopausal exposed women is consistent with data on male smelter workers, whereas the relation found for premenopausal women is significantly lower. This suggests that sex plays an important role in the metabolism of lead, and current models of exposure extrapolated from male data may be inappropriate for use on women.

In vivo K-shell X-ray fluorescence bone lead measurements in young adults

The (109)Cd K-shell X-ray fluorescence (XRF) technique was used to measure in vivo tibia lead concentrations of 34 young adults living in the state of Vermont (USA) and the province of New Brunswick (Canada). The subjects ranged in age from 18 to 35 years, and had no known history of elevated lead exposure. Measurement parameters were varied, using the same XRF system for both populations. Tibia lead concentrations were low for both groups, with mean values of 0.7 microg lead g(-1) bone mineral (Vermont) and 0.5 microg g(-1)(New Brunswick). No individual measurement exceeded 7 microg g(-1). Mean uncertainty values obtained for the Vermont and New Brunswick subjects were 4.1 microg g(-1) and 2.6 microg g(-1), respectively. Improved measurement uncertainty in the New Brunswick group was attributed to the use of a reduced source-to-skin distance (approximately 5 mm) and a longer measurement time (3600 seconds) using a weaker radioisotope source (< or =0.42 GBq). Measurement uncertainty tended to increase with body mass index. For a given body mass index, female subjects returned a measurement uncertainty approximately 1 microg g(-1) greater than males.

In vivo tibial lead measurement to assess the health hazard of Venezuelan workers

Gamma-ray induced X-ray emission (GIXE) technique for elemental lead in-vivo tibial measurement using a large volume hyper pure germanium detector is presented with the most convenient source-sample-detector geometry. The system operates advantageously when several parameters are considered for a lower dead time operation. The detection limit (DL) is better that 3.5 μg/g of Ca. Results of in-vivo average tibial lead concentration for some of the monitored groups are: control 7 μg of lead per g of Ca; gasoline filling attendants 6 μg/g of Ca; custom office workers near the DL; industrial workers range from DL up to 84±3 μg/g of Ca, suggesting that lead accumulation in the bone does not represent a major health risk

L-shell x-ray fluorescence measurements of lead in bone: accuracy and precision

This study aimed to quantify the accuracy and precision of a method for in vivo measurements of lead in bone using L-shell x-ray fluorescence (LXRF), the former via comparison with independent measurements of lead in bone obtained using electrothermal atomic absorption spectrometry (AAS) following acid digestion. Using LXRF, the lead content of adult human cadaver tibiae was measured, both as intact legs and as dissected tibiae with overlying tissue removed, the latter at several proximal–distal locations. After LXRF, each tibia was divided into nine cross-sectional segments, which were further separated into tibia core and surface samples for AAS measurement. The proximal–distal variability of AAS-measured core and surface tibia lead concentrations has been described elsewhere (the lead concentration was found to decrease towards both ends of the tibia). The subjects of this paper are the proximal–distal variability of the LXRF-measured lead concentrations, the measurement uncertainty and the statistical agreement between LXRF and AAS. There was no clear proximal–distal variability in the LXRF-measured concentrations; the degree of variability in actual tibia lead concentrations is far less than the LXRF measurement uncertainty. Measurement uncertainty was dominated by counting statistics and exceeded the estimate of lead concentration in most cases. The agreement between LXRF and AAS was reasonably good for bare bone measurements but poor for intact leg measurements. The variability of the LXRF measurements was large enough, for both bare bone and intact leg measurements, to yield grave concerns about the analytical use of the technique in vivo.

Individual Variability in Human Tibia Lead Concentration

Individual Variability in Human Tibia Lead Concentration

Individual variability in human tibia lead concentration.

Our aims in this study were to determine proximal-distal variability in adult human tibia lead concentration via electrothermal atomization atomic absorption spectrometry (ETAAS) and to determine whether there were any differences between core and surface tibia lead concentrations. We analyzed duplicate core and surface tibia samples for lead at multiple proximal-distal sections on 10 adult human cadaver legs. Dried bone samples were digested in nitric acid using microwave-assisted heating, and lead content was determined by ETAAS with Zeeman background correction. Lead concentrations in nine tibiae (one tibia was excluded because some of the data were compromised) ranged from 3.1 to 27.9 microg lead/g of dry bone. Both core and surface tibia lead concentrations were lower at the proximal and distal ends of the tibia. Surface tibia lead was approximately 5 microg/g greater than core tibia lead in six tibiae with relatively low lead concentration, and 8 microg/g greater in three tibiae with relatively high lead concentration. The difference between core and surface tibia lead was independent of proximal-distal tibia location. We conclude that these nine human tibiae showed a greater surface tibia lead concentration than core tibia lead concentration. This observation has consequences for the noninvasive measurement of tibia lead via K-shell and L-shell X-ray fluorescence.

A pilot evaluation of tibia lead concentrations in Taiwan.

The aims of this study were to examine some of the factors that influence tibia lead concentrations, tibia lead x-ray fluorescence measurement uncertainty and blood lead concentrations, and to compare tibia lead concentrations in Taiwanese lead workers to those observed in lead workers from other countries. A pilot evaluation of 43 adult lead workers who underwent measurements of tibia lead and blood lead concentrations. Mean and maximum tibia lead concentrations were 54 microg of Pb per g of bone mineral(microg/g) and 193 microg/g, respectively. Mean and maximum blood lead concentrations were 44 microg/dl and 92 microg/dl, respectively. Past occupational control of lead exposure in Taiwan, ROC, did not prevent these workers from accumulating tibia lead concentrations greater than those in similar workers elsewhere in the world.

The effects of retained lead bullets on body lead burden.

Numerous case reports have demonstrated that lead poisoning with potentially fatal consequences can result from retained lead projectiles after firearm injuries. To assess the impact of retained projectiles on subsequent lead exposure in the population, one cannot rely on self-selected cases presenting with symptoms of lead intoxication. This preliminary study seeks to identify increased lead burden and identify risk factors of elevated blood lead levels for individuals with retained lead bullets. Forty-eight patients were originally recruited from gunshot victims presenting for care at the King/Drew Medical Center in Los Angeles, California. An initial blood level was measured for all recruited patients and repeated for the 28 participants available for follow-up, 1 week to 8 months later. Medical history, including a history of prior firearm injuries and other retained projectiles, was taken, along with a screening and risk factor questionnaire to determine other sources of lead (occupational/recreational) to which the patient might have been, or is at present, exposed. The participants also had K-shell x-ray fluorescence determinations of bone lead in the tibia and calcaneus in order to determine past lead exposures not revealed by medical history and risk factor questionnaire. Multivariate models of blood level were made using risk factor and bone lead concentration data. We demonstrated that blood lead tends to increase with time after injury in patients with projectile retention, and that the increase in significant part depended on the presence of a bone fracture caused by the gunshot. We encountered evidence suggesting that the amount of blood lead increase in time after injury is also dependent on the tibia lead concentration. There were too few cases in the study to fully test the effects of bullet location, or the interaction of bullet location with bone fracture or bullet fragmentation.

Seasonal Variation in Bone Lead Contribution to Blood Lead during Pregnancy

Population blood lead level (PbB) often shows seasonal variation, frequently being higher in summer and lower in winter. As vitamin D metabolites also show seasonal variability, and the metabolites are associated with bone metabolism, some authors have posited a role for bone lead release in seasonal PbB changes. We made third trimester and postdelivery PbB measurements on 414 immigrant women (98% Latina) in Los Angeles. We measured in vivo tibia and calcaneus (heel) lead concentration postdelivery via K-shell X-ray fluorescence. We saw evidence of seasonal variation in prenatal PbB, but not postnatal PbB. PbB was highest in spring and lowest in autumn. Tibia lead concentration was associated with prenatal PbB, as reported before. The contribution of tibia lead to prenatal PbB varied seasonally, with the greatest contribution occurring in the winter quarter and the least in the summer quarter. The temporal pattern of bone lead contribution to PbB follows the seasonal alteration of insolation. There was no seasonal component in prenatal PbB associated with calcaneus lead, nor were there seasonal variations in either calcaneus or tibia lead contributions to postnatal PbB. Bone turnover in the third trimester of pregnancy may be higher in winter months than in summer months, resulting in greater fetal lead exposure in spring than at other times of the year.

Predictors of DMSA chelatable lead, tibial lead, and blood lead in 802 Korean lead workers

OBJECTIVESTo examine the interrelations among chelatable lead (by dimercaptosuccinic acid, DMSA), tibial lead, and blood lead concentrations in 802 Korean workers with occupational exposure to lead and 135 employed controls...

Longitudinal changes in bone lead concentration: implications for modelling of human bone lead metabolism.

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.

Bone Lead Levels and Language Processing Performance

The relation between bone lead absorption and language processing abilities in 156 randomly selected 11- to 14-year-old boys who were asymptomatic for lead toxicity is examined. Tibial lead concentrations were measured by X-ray fluorescence spectroscopy. The language processing outcome variables consisted of the least and most difficult subtests from the Nonword Repetition Task, Competing Language Processing Task, and the Revised Token Test. Participants were classified by quartiles according to bone lead concentrations, and analysis of variance and analysis of covariance measured the impact on language processing scores. Results showed that children in the highest bone lead quartile displayed decreased language processing performance on the most difficult language processing tasks but not on the easier tasks.