Bone Lead Measurements Research Articles

Bone lead measurements of live condors in field to assess cumulative lead exposure.

Lead poisoning remains the leading cause of diagnosed death for critically endangered California condors, which are annually monitored for lead exposure via blood tests. Blood tests are generally reflective of acute lead exposure. Since condors are victims to both chronic and acute lead exposure, measuring bone, which in humans is reflective of years to decades worth of exposure, is a valuable biomarker. In this study, we measured bone Pb of the tibiotarsus of 64 condors in vivo using a portable x-ray fluorescence device. The average uncertainty for measurements, typically reflective of how effective the device performed, was found to be 3.8 ± 2.2µg/g bone mineral. The average bone lead level was found to be 26.7 ± 24.5µg/g bone mineral. Bone lead correlated significantly with a sum of all blood lead measures over the lifetime of each condor. In the future, bone lead can potentially be used to inform treatment planning and address the chronic health implications of lead in the species.

Portable x-ray fluorescence for bone lead measurement: Current approaches and future directions.

Legacy lead exposures persist as a widespread problem. Blood lead is traditionally used for lead exposure surveillance; however, bone lead proves to be a cheaper, more accessible, and more revealing tool for surveillance that can be measured using portable x-ray fluorescence techniques. We outline how this approach excels for bone lead measurements. Portable XRF offers quick, non-invasive in vivo quantification of bone lead. Compared to traditional KXRF systems, pXRF is limited to cortical bone but allows for quicker and similar results. Current methodologies of lead exposure need re-evaluation as lead-related disease burden and trends are dependent on both cumulative and acute impacts. We examined the evolution of XRF techniques for measuring bone lead, comparing current methods with previous ones. We assessed their accuracy, identified limitations, and discussed potential advances in future techniques. Legacy lead exposures call for a revitalization of lead surveillance methods, and pXRF measurement of bone lead offers such a solution.

The feasibility of K XRF bone lead measurements in mice assessed using 3D-printed phantoms

This article describes the development of a system for in vivo measurements of lead body burden in mice using 109Cd K x-ray fluorescence (XRF). This K XRF system could facilitate early-stage studies on interventions that ameliorate or reverse organ tissue damage from lead poisoning by reducing animal numbers through a cross-sectional study approach. A novel mouse phantom was developed based on a mouse atlas and 3D-printed using PLA plastic with plaster of Paris ’bone’ inserts. PLA plastic was found to be a good surrogate for soft tissue in XRF measurements and the phantoms were found to be good models of mice. As expected, lead detection limits varied with mouse size, mouse orientation, and mouse position with respect to the source and detector. The work suggests that detection limits of 10 to 20 μg Pb per g bone mineral may be possible for a 2 to 3 hour XRF measurement in a single animal, an adequate limit for some pre-clinical studies. The 109Cd K XRF mouse measurement system was also modeled using the Monte Carlo code MCNP. The combination of experiment and modeling found that contrary to expectation, accurate measurements of lead levels in mice required calibration using mouse-specific calibration standards due to the coherent scatter peak normalization failing when small animals are measured. MCNP modeling determined that this was because the coherent scatter signal from soft tissue, which until now has been assumed negligible, becomes significant when compared to the coherent scatter signal in bone in small animals. This may have implications for some human measurements. This work suggests that 109Cd K x-ray fluorescence measurements of lead body burden are precise enough to make the system feasible for small animals if appropriately calibrated. Further work to validate the technology’s measurement accuracy and performance in vivo will be required.

Bone lead variability in bone repository skeletal samples measured with portable x-ray fluorescence

Bone lead serves as a better, more accessible biomarker to many communities experiencing chronic exposure to lead. A new method using low energy x-ray fluorescence in a handheld device (portable XRF) allows us to measure this chronic biomarker in only a few minutes. However, many unknowns remain about this biomarker measured using a new low energy x-ray technique. The low energy of the new method was theorized to measure a slightly different portion of the bone than previous techniques, which could influence measurements at different bone sites and types. We tested how bone measurements varied across five bone sites: mid-tibial shaft, proximal tibia, distal tibia (ankle), ilium, and cranium. We found bone lead measurements are not significantly different between skeletal elements when measured using a portable XRF. On average, bone lead in the repository samples was measured to be 21.6 ± 21.3 μg/g with an XRF detection limit of 2.1 ± 0.5 μg/g. Cumulative lead exposure can be effectively measured using the portable XRF on a variety of bone types, but the tibia should be preferentially measured to compare between studies and individuals.

Expanding the use of portable XRF to monitor lead exposure in an Australian duck species two decades after a ban on lead shot

There is growing worldwide recognition of the threat posed by toxic lead for wildlife and humans. Lead toxicity from ammunition has been shown to be a threat to waterbirds across the globe. Lead shot was banned for all waterfowl hunting in Victoria, Australia, in 2002. However, no assessments of lead exposure in Australian waterfowl have been published since the 1990s. Our aim was to estimate contemporary lead exposure via measuring bone lead concentrations in a harvested dabbling duck, the Pacific black duck (Anas superciliosa). We collected wings from 77 Pacific black ducks, spanning 2018 (n = 30) and 2021 (n = 47), from nine sites with long-term histories of regular waterfowl hunting. We sought to validate portable X-ray fluorescence (XRF) for this purpose by taking a piece of humerus bone from each bird, and measuring lead concentration (mg/kg), first via non-destructive XRF and then via destructive inductively coupled plasma mass spectrometry (ICP-MS) and validated the relationship via regression analysis. Portable XRF bone lead measurement demonstrated a strong correlation with ICP-MS results using root-transformed regression (R2 = 0.85). Greater than 92 % of ducks had only background lead exposure (<10 mg/kg). When compared to historical studies in the same species at similar field sites from the 1990s, lead exposure levels were considerably lower, with mean lead concentrations ∼2-fold lower (3.7 c.f. 7.7 mg/kg), and the frequency of birds with severe lead exposure (>20 mg/kg) ∼3-fold lower (2.6 c.f. 7.5 %). Our results confirm that portable XRF is a useful option for measurement of bone lead in Australasian waterbird species. Our findings also demonstrate that a ban on the use of lead shot around 20 years ago has been associated with a substantial reduction in lead exposure in at least one species of waterfowl.

Predicting cumulative lead (Pb) exposure using the Super Learner algorithm

Chronic lead (Pb) exposure causes long term health effects. While recent exposure can be assessed by measuring blood lead (half-life 30 days), chronic exposures can be assessed by measuring lead in bone (half-life of many years to decades). Bone lead measurements, in turn, have been measured non-invasively in large population-based studies using x-ray fluorescence techniques, but the method remains limited due to technical availability, expense, and the need for licensing radioactive materials used by the instruments. Thus, we developed prediction models for bone lead concentrations using a flexible machine learning approach--Super Learner, which combines the predictions from a set of machine learning algorithms for better prediction performance. The study population included 695 men in the Normative Aging Study, aged 48 years and older, whose bone (patella and tibia) lead concentrations were directly measured using K-shell-X-ray fluorescence. Ten predictors (blood lead, age, education, job type, weight, height, body mass index, waist circumference, cumulative cigarette smoking (pack-year), and smoking status) were selected for patella lead and 11 (the same 10 predictors plus serum phosphorus) for tibia lead using the Boruta algorithm. We implemented Super Learner to predict bone lead concentrations by calculating a weighted combination of predictions from 8 algorithms. In the nested cross-validation, the correlation coefficients between measured and predicted bone lead concentrations were 0.58 for patella lead and 0.52 for tibia lead, which has improved the correlations obtained in previously-published linear regression-based prediction models. We evaluated the applicability of these prediction models to the National Health and Nutrition Examination Survey for the associations between predicted bone lead concentrations and blood pressure, and positive associations were observed. These bone lead prediction models provide reasonable accuracy and can be used to evaluate health effects of cumulative lead exposure in studies where bone lead is not measured.

Portable X-ray fluorescence for bone lead measurements of Australian eagles

Lead (Pb) toxicity from ammunition has been shown to be a threat to scavenging birds across the globe. Toxic levels of lead have recently been found in Australia's largest bird of prey, the wedge-tailed eagle (Aquila audax), through inductively coupled plasma mass spectrometry (ICP-MS) analysis of liver and bone samples. However, ICP-MS is consumptive (causing damage to archived specimens), time-consuming, and expensive. For these reasons, portable X-ray fluorescence (XRF) devices have been optimized to measure bone lead in North American avian species, humans, and other environmental samples. In this study, we assessed portable XRF for bone lead measurement in Australian raptors in two parts. First, we validated the method using tissues from wedge-tailed eagles from Tasmania (A. a. fleayi), analysing bone samples taken from sites on the femur immediately adjacent to sites for which we had ICP-MS data (n = 89). Second, we measured lead via portable XRF in the skulls of wedge-tailed eagles from south-eastern mainland Australia (A. a. audax) collected during a criminal prosecution (n = 92). Portable XRF bone lead measurement demonstrated an excellent correlation with ICP-MS results using root-transformed regression (R2 = 0.88). Calculated equivalent ICP-MS values revealed that greater than 50% of the eagles from mainland Australia had elevated lead levels (>10 mg/kg) and 13% had severe lead exposure (>20 mg/kg). Our results support previous studies of North American avian species and suggest that portable XRF could be a useful and inexpensive option for measurement of bone lead in Australian scavenger species.

Do We Underestimate Risk of Mortality due to Lead Exposure?

Background/Aim: Studies using data from the National Health and Nutrition Examination Survey-III (NHANES-III) have demonstrated significant associations between blood lead levels and increased mortality. However, blood lead reflects primarily recent exposure and lead mobilized from internal organs. Bone lead represents cumulative lead burden and thus is a better biomarker for assessing chronic impacts, but its in vivo assessment requires special K-x-ray fluorescence (KXRF) instrumentation. Our team used KXRF measurements of lead in bone and blood lead levels in participants of the Normative Aging Study to develop an algorithm predicting bone lead levels from a combination of blood lead levels and standard biochemical, hematologic, and questionnaire data. We examined the associations of our algorithm-estimated bone lead levels and mortality in NHANES-III.Methods: We included 11,065 adults followed up to December 31, 2015. Estimated tibia and patella bone lead levels were calculated using our prediction algorithm. We used survey-weighted Cox proportional hazards models to compute hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During the median follow-up of 22.4 years (216,565 person-years), 4,103 participants died (mortality rate=1,895 per 100,000 adults/year). Means (95% CIs) of blood lead, tibia lead, and patella lead were 3.47 μg/dL (3.27-2.67), 2.98 μg/g (2.23-3.75), and 3.04 μg/g (1.94-4.14), respectively. After adjustment for potential confounders, the HRs comparing participants at the 90th vs. 10th percentiles of exposure with regards to all-cause mortality were 1.25 (95% CI: 1.05-1.50) for blood lead, 1.91 (1.36-2.68) for tibia lead, 2.00 (1.45-2.77) for patella lead; for CVD mortality, 1.67 (1.20-2.34) for blood lead, 1.89 (0.98-3.67) for tibia lead, 2.24 (1.26-4.00) for patella lead; and for cancer mortality, 1.35 (0.98-1.84) for blood lead, 2.52 (1.30-4.90) for tibia lead, 2.45 (1.29-4.66) for patella lead.Conclusions: These findings suggest that risk assessment based on blood lead levels may underestimate the true mortality risk of lead exposure.

Estimating the causal effect of prenatal lead exposure on prepulse inhibition deficits in children and adolescents

During pregnancy, maternal lead from earlier exposures mobilizes and crosses placental barriers, placing the developing fetus at risk for lead exposure and neurodevelopmental deficits. Some neuronal circuits known to be affected in neurodevelopment disorders can be probed with simple physiological behavioral paradigms. One such neural biomarker is Pre-Pulse Inhibition (PPI), an indicator of adequate sensorimotor gating processing. In clinical studies, deficits in PPI have been associated with neurodevelopmental disorders in human subjects. To our knowledge, no studies have examined the use of PPI as a biomarker of toxicant effects on the brain in epidemiological studies. We aimed to estimate the causal effect of prenatal lead exposure, assessed by maternal cortical bone lead concentrations, on PPI in 279 children from Mexico City. in vivo maternal cortical bone lead measurements were taken at four weeks postpartum at the mid-tibia shaft using a K-Shell X-ray fluorescence instrument. PPI recording occurred in an isolated clinical setting and eye blink responses were measured using electromyography. We assessed if the conditions for causal inference held in our study and used the results of our assessment to estimate the causal effect of prenatal lead exposure on PPI using an ordinary least squares regression model, a marginal structural model, and the parametric g-formula. Results were consistent across the three modeling approaches. For the parametric g-formula, a one standard deviation (10.0 μg/g) increase in prenatal lead significantly reduced PPI by approximately 19.0 % (95 % CI: 5.4 %, 34.3 %). This decrease is similar in magnitude to clinical studies on schizophrenia, which have observed PPI impairments in patients with schizophrenia as compared to controls. Our results are consistent with findings from other studies establishing an association between lead exposure and neurodevelopmental disorders in children and suggest that PPI may be useful as an objective biomarker of toxicant effects on the brain.

A study protocol to determine the association between lifetime lead exposure and violent criminal behaviour in young males in conflict with the law

BackgroundLow-level lead exposure has harmful and persistent effects on behaviour. Recent studies have linked environmental lead exposure and the development of aggressive, violent and criminal behaviour. This protocol is designed to study an association between lifetime (bone) lead levels and violent criminal behaviour among young males in conflict with the law in Gauteng youth development centres.MethodsThis paper describes a study to determine a link between lifetime lead exposure and violent criminal behaviour. Lifetime lead exposure will be measured using bone lead measurement, while blood lead levels will be observed for current exposure. Thereafter, criminal records of participants will be reviewed whereas violent behaviour and risk factors will be observed using a questionnaire. The study focused on young males in conflict with the law in three centres within Gauteng Provence, South Africa. After stratifying the centres, we randomly selected participants. The researcher shall adhere to ethical requirements throughout the study. Data will be analysed for descriptive and inferential analysis using Statistical Package for Social Science (SPSS).DiscussionThe study will provide a strong foundation for an improved understanding of the relationship between environmental contamination from lead exposure and aggression/violent criminal behaviour. Beyond the health sector, the study findings may be able to inform new approaches to crime prevention through environmental action with an emphasis on the role of non-health sectors.

Comparison of bone lead measured via portable x-ray fluorescence across and within bones

BackgroundBone lead measured via x-ray fluorescence (XRF) has been used for decades in health studies. A portable XRF device for bone lead measurement is gaining in popularity for its ease of use and shorter measurement times. Previous XRF devices have measured different bone types in order to sample both cortical and trabecular bone, in which lead has different half residence times. ObjectiveThe portable XRF uses lower energy to measure bone lead than previous devices, and, thus, only measures the surface of the bone. Because all bones have a cortical shell, we hypothesized that portable XRF bone lead measurements would be similar regardless of the bone measured. MethodsThis study tested differences in portable XRF bone lead measurements across different cortical and trabecular bones in measurements made on 31 cadavers. We also compared tissue thicknesses overlying different bones, which can impact portable XRF measurements. ResultsThe correlation coefficients found between bones were higher (rho ~0.4) than previous K-shell XRF bone measurements in cortical and trabecular over the same range of values (rho~0.2). The concentrations were shown to vary non-significantly across different bones within individuals.

Improvements and reproducibility of an optimal grazing-incidence position method to L-shell x-ray fluorescence measurements of lead in bone and soft tissue phantoms

L-shell x-ray fluorescence (LXRF) is a non-invasive approach to lead (Pb) concentration measurements in human bone. The method is based on the detection of the characteristic x-ray photons of Pb at 10.5 and 12.6 keV and experimental studies were designed to perform in vivo human bone Pb measurements. In later studies, however, the initial LXRF methodology was shown to have poor accuracy and precision. In a recent publication, we investigated an optimal grazing-incidence position (OGIP) approach using a sub-millimeter x-ray beam from an integrated x-ray tube and polycapillary x-ray lens table-top system. The OGIP method effectively reduced the x-ray scatter and produced a Pb detection limit of ∼5 μg/g for a 2 mm soft tissue phantom thickness. In this study, the OGIP methodology was improved by using 10 s x-ray spectra acquisitions at sequential positions 0.5 mm apart. The measured Sr Kα peak height versus position data was used to spectroscopically identify the bone phantom and the OGIP. The data was fitted with the analytical convolution between a Gaussian and an exponential decay. The position corresponding to the maximum of the fitted convolution function was then selected as the OGIP. Four phantom sets were used. A cylindrical plaster-of-Paris bone phantom doped with Pb in a concentration of 74 μg/g was used as a bare bone phantom or with one of the three overlying polyoxymethylene cylindrical shell soft tissue phantoms of 1, 2, and 3 mm thickness. The reproducibility of the OGIP method was assessed in five independent trials using each of the four phantom sets. The coefficient of variation (COV) percentage values of the Sr Kα peak height measurements were below 5%. The new procedure decreased by more than threefold the duration and radiation dose of the earlier approach.

Bone Lead Associations with Blood Lead, Kidney Function, and Blood Pressure among U.S. Lead-Exposed Workers in a Surveillance Program

Background: Measurements of lead in bone represent cumulative exposure which, in many studies, has been more strongly associated with lead effects than blood lead (BL), which represents recent exposure. Aim: Determine whether maximum BL in the past is correlated with current bone lead and compare associations of bone lead with kidney function and blood pressure (BP) among workers. Methods: Adult men in a lead surveillance program living within 200 miles of New York City were enrolled during 2016-2017. Participants had tibia lead measured via K-shell X-ray fluorescence, BP taken, and blood drawn to measure BL and estimated glomerular filtration rate (eGFR). Maximum past BL was obtained from occupational surveillance programs (mean year first BL 1997). eGFR was calculated using serum creatinine and cystatin C. Multivariable linear and logistic regression models were used to determine associations with bone lead. Systolic and diastolic BP models excluded participants taking BP medicine. Results: Among 211 participants, median (interquartile range) bone lead, current BL, and maximum past BL were 13.8 (9.4-19.5) mg of lead per gram of bone mineral, 2.5 (1.5-4.4) mg/dl, and 29.0 (14.0-38.0) mg/dl, respectively. Maximum past BL, but not current blood lead, significantly predicted current bone lead in adjusted analyses (p&amp;lt;0.0001, model R-square&amp;#61;0.27). In adjusted models, bone lead was moderately associated with low eGFR (bone lead odds ratio and 95% CI per 10 mg of bone lead for eGFR&amp;lt;60 &amp;#61; 1.34 [0.97-1.87]; the regression coefficient and p-value for continuous eGFR was also significant [p&amp;#61;0.05], model R-square&amp;#61;0.29). Bone lead in adjusted analyses was associated with increased systolic BP (regression coefficient&amp;#61;0.36, p&amp;#61;0.02, model R-square&amp;#61;0.16). There were no associations between current blood lead and eGFR or BP. Conclusion: Bone lead was significantly correlated with past maximum BL and was associated with modest decreases in eGFR and increases in systolic BP.

Association of Lead Exposure on Cognitive Decline due to Mediation and Interaction with Uric Acid

BACKGROUND: Low-level cumulative lead exposure has been associated with cognitive decline in adults. Previous studies suggest that lead increases levels of the antioxidant uric acid and that uric acid may also predict changes in cognitive function. We explored whether uric acid mediated or interacted with lead in the association between lead exposure and cognitive decline.METHODS: From 1991 to 2002, a subset of the Normative Aging Study cohort of community-dwelling men was assessed for cumulative lead exposure in the tibia and patella bones. The Mini-Mental State Examination (MMSE) was administered as a test of global cognition starting in 1992. We conducted formal mediation analysis using the first bone lead measurement, uric acid concurrent with baseline MMSE, and the difference between the second and baseline MMSE scores, adjusted for age at baseline MMSE, education, serum creatinine, smoking status and pack-years, drinking status, and years between the two MMSE tests.RESULTS: 552 men [mean (standard deviation) age: 67.27 (6.52)] took two MMSE tests that were 3.92 (1.80) years apart and had valid bone lead measurements. The total change in MMSE score for an interquartile range (20 µg/g) increase in patella lead was -0.29 (95% confidence interval: -0.49, -0.08) (p&amp;#61;0.007), due mostly to the direct association with lead [-0.25 (-0.44, -0.06) (p&amp;#61;0.01)] when uric acid was set to the mean value; the component due to interaction only was -0.03 (-0.07, 0.004) (p&amp;#61;0.08), due to mediation and interaction was 0.02 (-0.001, 0.05) (p&amp;#61;0.06), and due to mediation only was -0.03 (-0.07, 0.01) (p&amp;#61;0.20). Results with tibia lead were less robust.CONCLUSIONS: Prior studies have indicated significant effects of patella lead on cognitive decline, but accounting for uric acid may be needed to understand the full association between lead and cognitive decline.

Lead exposure biomarkers in the Common Loon

Lead in fishing tackle is a significant source of exposure to the environment, wildlife, and potentially humans. Common Loons (Gavia immer) are exposed to lead by eating fish which have lead tackle, or ingesting fishing weights or spent ammunition when they ingest small stones to aid in digestion. Blood lead is traditionally used as a biomarker of exposure in loons, but it only reflects recent exposures. Cumulative exposure measured via bone lead may better reflect the overall health of loons and their aquatic habitat. This study compared a portable x-ray fluorescence (XRF) device for measurement of bone lead with and without tissue overlying the bone on loon cadavers with measurements made by inductively coupled plasma mass spectrometry (ICP-MS) of different tissues from the loons. For this study we had 75 bone samples, 19 body fluid samples, and 17 liver lead samples. We found significant correlations between portable XRF bone lead measurements made with overlying tissue and ICP-MS measures of bone lead (R = 0.88), body fluid lead (R = 0.65), and liver lead (R = 0.71). Bone lead was found to be higher in loons collected from non-coastal regions. In assessing lead-related cause of death, bone lead proved more predictive than liver lead. Future studies should investigate the value of these biomarkers for both aquatic health and loon health to further validate our findings.

Childhood lead biokinetics and associations with age among a group of lead-poisoned children in China.

Childhood lead exposure has been shown to have a significant effect on neurodevelopment. Many of the biokinetics involved with lead biomarkers in children still remain unknown. Two hundred fifty (157 in the exposed group and 93 controls) children were enrolled in our study and lead exposed children returned for multiple visits for measurement of blood and bone lead and chelation treatment. We demonstrated that the correlation between blood and bone lead increased with subsequent visits. We calculated the blood lead half-life for 50 patients, and found a significant (p-value <0.001) positive correlation with age. For ages 1-3 years (n=17), the blood lead half-life was found to be 6.9 ± 4.0 days and for 3+ years it was found to be (n=33) 19.3 ± 14.1 days. In conclusion, the turnover of lead in children is faster than in adults. Our results indicate that blood lead is a more acute biomarker of exposure than previously thought, which will impact studies of children’s health using blood lead as a biomarker.

Feasibility of a portable X-ray fluorescence device for bone lead measurements of condor bones

Lead based ammunition is a primary source of lead exposure, especially for scavenging wildlife. Lead poisoning remains the leading cause of diagnosed death for the critically endangered California condors, which are annually monitored via blood tests for lead exposure. The results of these tests are helpful in determining recent exposure in condors and in defining the potential for exposure to other species including humans. Since condors are victim to acute and chronic lead exposure, being able to measure both would lend valuable information on the rates of exposure and accumulation through time. A commercial portable X-ray fluorescence (XRF) device has been optimized to measure bone lead in vivo in humans, but this device could also be valuable for field measurements of bone lead in avian species. In this study, we performed measurements of bone Pb in excised, bare condor bones using inductively coupled plasma mass spectrometry (ICP-MS), a cadmium 109 (Cd-109) K-shell X-ray fluorescence (KXRF) system, and a portable XRF system. Both KXRF and portable XRF bone Pb measurement techniques demonstrated good correlations with ICP-MS results (r=0.93 and r=0.92 respectively), even with increasing skin thickness (r=0.86 between ICP-MS and portable XRF at 1.54mm of soft tissue). In conclusion, our results suggest that a portable XRF could be a useful option for measurement of bone Pb in avian species in the field.

Noninvasive Determine Lead Poisoning Biomarker for Human Body—Design and Manufacture on Innovated New-XRF Analyzer of Bone Lead

This research introduces an important noninvasive technique which is In vivo measurement of human body bone lead. It makes use of the miniature X tube emitting X-ray through sebum to stimulate the characteristic X fluorescence at the position of tibia under its surface about 1 ～ 1.5 mms. The characteristic X fluorescence which express bone lead content and asking for help from Si-PIN detector and M.C.A analysis system to output a bone lead density d. This technique use the relative functions between sebum thick t and spectrum- unfolding area for bone lead peak. The Compton scatter integral value C could represent sebum thick. It will be calculated the lead content of tibia with ppm .The experiment of this instrument measured 52 data gained by volunteers. This measurement results with other measuring results by international researches are mutually fits together. Thus it is credible that the N-XRF instrument can be possible in vivo to measure bone lead in human body.

Theoretical modeling of a portable x-ray tube based KXRF system to measure lead in bone

Objective. K-shell x-ray fluorescence (KXRF) techniques have been used to identify health effects resulting from exposure to metals for decades, but the equipment is bulky and requires significant maintenance and licensing procedures. A portable x-ray fluorescence (XRF) device was developed to overcome these disadvantages, but introduced a measurement dependency on soft tissue thickness. With recent advances to detector technology, an XRF device utilizing the advantages of both systems should be feasible.Approach. In this study, we used Monte Carlo simulations to test the feasibility of an XRF device with a high-energy x-ray tube and detector operable at room temperature.Main Results. We first validated the use of Monte Carlo N-particle transport code (MCNP) for x-ray tube simulations, and found good agreement between experimental and simulated results. Then, we optimized x-ray tube settings and found the detection limit of the high-energy x-ray tube based XRF device for bone lead measurements to be 6.91 µg g−1 bone mineral using a cadmium zinc telluride detector.Significance. In conclusion, this study validated the use of MCNP in simulations of x-ray tube physics and XRF applications, and demonstrated the feasibility of a high-energy x-ray tube based XRF for metal exposure assessment.

Cumulative lead exposure is associated with reduced olfactory recognition performance in elderly men: The Normative Aging Study

IntroductionOlfactory dysfunction has been identified as an early warning sign for Alzheimer's disease, Parkinson's disease, dementia and more. A few occupational and environmental exposures have also been associated with reduced olfactory function, although the effects of long term environmental exposure to lead on olfactory dysfunction have not been explored. Here we performed olfactory recognition testing in elderly men in a community-dwelling cohort and examined the association with cumulative lead exposure, as assessed by lead in tibial and patellar bone. MethodsOlfactory recognition was measured in 165 men from the Normative Aging Study (NAS) who had previously taken part in bone lead measurements using K-X-ray fluorescence (KXRF). Olfactory recognition was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Associations between olfactory recognition, global cognition and cumulative lead exposure were estimated using linear regression, with additional adjustment for age, smoking, and functional polymorphism status for hemochromatosis (HFE), transferrin (TfC2), glutathione-s-transferase Pi1 (GSTP1) and apolipoprotein E (APOE) genotypes. Sensitivity analyses explored olfactory recognition in men with high global cognitive function as measured using the Mini-Mental Status Exam (MMSE). ResultsThe average age of the NAS participants at the time of olfactory recognition testing was 80.3 (standard deviation or SD=5.7) years. Mean tibia lead was 16.3 (SD=12.0)μg/g bone, mean patella lead was 22.4 (SD=14.4)μg/g bone, and mean UPSIT score was 26.9 out of 40 (SD=7.0). Consistent with previous findings, age at olfaction testing was negatively associated with UPSIT score. Tibia (but not patella) bone lead was negatively associated with olfaction recognition (per 15μg/g tibia lead: β=−1.57; 95% CI: −2.93, −0.22; p=0.02) in models adjusted for smoking and age. Additional adjustment for education did not significantly change results. Of all the genes explored, only the presence of one or more HFE variant alleles was significantly associated with olfaction recognition (HFE β=2.26; 95% CI: 0.09, 4.43; p=0.04). In a model containing the HFE term and a lead term, the tibia lead parameter estimate dropped by 21% (per 15μg/g tibia lead: β=−1.25; 95% CI: −2.64, 0.14; p=0.08) while the HFE term dropped 15% (β=1.91; 95% CI: −0.28, 4.10; p=0.09). None of the other gene terms were associated with olfactory recognition in this cohort, nor were any gene–lead interaction terms significant. Additional sensitivity analysis in men with MMSE scores of 25 or higher (n=149) showed a similar but slightly attenuated association between lead and olfactory recognition (per 15μg/g tibia lead β=−1.39; 95% CI: −3.00, 0.22; p=0.09). ConclusionCumulative exposure to lead is associated with reduced olfactory recognition in a cohort of elderly men. The association was similar but not significant in men with better cognitive function as measured by the MMSE. Iron metabolism gene status may also affect olfactory function.