Quantification of manganese and mercury in toenail in vivo using portable X-ray fluorescence (XRF).

BACKGROUND AND OBJECTIVE: Toenail is an advantageous biomarker to assess exposure to metals such as manganese and mercury. Toenail Mn and Hg are in general analyzed by chemical methods such as inductively coupled plasma mass spectrometry and atomic absorption spectrophotometry. In this project, a practical and convenient technology-portable X-ray florescence (XRF)-is studied for the noninvasive in vivo quantification of manganese and mercury in toenail. MATERIAL AND METHODS: The portable XRF method has advantages in that it does not require toenail clipping and it can be done in 3 min, which will greatly benefit human studies involving the assessment of manganese and mercury exposures. This study mainly focused on the methodology development and validation which includes spectral analysis, system calibration, the effect of toenail thickness, and the detection limit of the system. Manganese- and mercury-doped toenail phantoms were made. Calibration lines were established for these measurements. RESULTS: The results show that the detection limit for manganese is 3.65 µg/g (ppm) and for mercury is 0.55 µg/g (ppm) using 1 mm thick nail phantoms with 10 mm soft tissue underneath. DISCUSSION AND CONCLUSION: We conclude that portable XRF is a valuable and sensitive technology to quantify toenail manganese and mercury in vivo.

In vivo measurement of bone manganese and association with manual dexterity: A pilot study.

We used neutron activation analysis (NAA) to measure hand bone manganese (BnMn) in 19 adult males. Median BnMn was 0.89µg/g dry bone (interquartile range = 1.07). After adjustment for age and occupation, higher ln(BnMn) was significantly associated with lower manual dexterity based on the Purdue Pegboard assembly task: ß = -1.77, standard error = 0.79, p = 0.04. Due to the small sample size, these results should be interpreted cautiously. BnMn appears to be a promising biomarker, and should be further studied.

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study.

BACKGROUND: Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. METHODS: In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. RESULTS: Among men 51-98 at baseline, higher patella Pb concentration (IQR: 21µg/g) was associated with -0.13 lower baseline MMSE (95% CI: -0.25, -0.004) and faster longitudinal MMSE decline (-0.016 units/year, 95% CI: -0.032, -0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: -0.026, -0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: -0.027, -0.002). We found weaker associations with tibia Pb. CONCLUSIONS: Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging.

XRF-measured bone lead (Pb) as a biomarker for Pb exposure and toxicity among children diagnosed with Pb poisoning.

Childhood lead (Pb) poisoning remains a global issue, especially in industrial areas. In this study, 115 children with average age 5.7 years were recruited as either patient diagnosed with Pb poisoning or controls at Xinhua Hospital in China. The subjects' bone Pb was measured with a K-shell X-ray fluorescence (KXRF) and a portable X-ray fluorescence (XRF) system. A significant correlation between KXRF bone Pb and blood Pb and portable XRF and KXRF measurements were observed. The half-life of blood-lead was calculated to be 9.96 ± 3.92 d. Our results indicate that bone is a useful biomarker for Pb in children.

Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.

BACKGROUND: Although the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness. METHODS: We examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements. RESULTS: Adjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 µg/g) and patella lead (20 µg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1. CONCLUSIONS: This study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.

Lead exposure and rate of change in cognitive function in older women.

BACKGROUND: Higher long-term cumulative lead exposure predicts faster cognitive decline in older men, but evidence of an association in women is lacking. OBJECTIVE: To determine if there is an association between lead exposure and cognitive decline in women. METHODS: This study considers a sample of 584 women from the Nurses' Health Study who live in or near Boston, Massachusetts. We quantified lead exposure using biomarkers of lead exposure assessed in 1993-2004 and evaluated cognitive decline by repeated performance on a telephone battery of cognitive tests primarily assessing learning, memory, executive function, and attention completed in 1995-2008. All cognitive test scores were z-transformed for use in analyses. We used linear mixed models with random effects to quantify the association between each lead biomarker and change in cognition overall and on each individual test. RESULTS: Consideration of individual tests showed greater cognitive decline with increased tibia lead concentrations, a measure of long-term cumulative exposure, for story memory and category fluency. The estimated excess annual decline in overall cognitive test z-score per SD increase in tibia bone lead concentration was suggestive, although the confidence intervals included the null (0.024 standard units, 95% confidence interval: -0.053, 0.004 - an additional decline in function equivalent to being 0.33 years older). We found little support for associations between cognitive decline and patella or blood lead, which provide integrated measures of exposure over shorter timeframes. CONCLUSIONS: Long-term cumulative lead exposure may be weakly associated with faster cognitive decline in community-dwelling women, at least in some cognitive domains.

Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence.

Mercury is a well-recognized environmental contaminant and neurotoxin, having been associated with a number of deleterious neurological conditions including neurodegenerative diseases, such as Alzheimer's disease. To investigate how mercury and other metals behave in the brain, we used synchrotron micro-X-ray fluorescence to map the distribution pattern and quantify concentrations of metals in human brain. Brain tissue was provided by the Rush Alzheimer's Disease Center and samples originated from individuals diagnosed with Alzheimer's disease and without cognitive impairment. Data were collected at the 2-ID-E beamline at the Advanced Photon Source at Argonne National Laboratory with an incident beam energy of 13 keV. Course scans were performed at low resolution to determine gross tissue features, after which smaller regions were selected to image at higher resolution. The findings revealed (1) the existence of mercury particles in the brain samples of two subjects; (2) co-localization and linear correlation of mercury and selenium in all particles; (3) co-localization of these particles with zinc structures; and (4) association with sulfur in some of these particles. These results suggest that selenium and sulfur may play protective roles against mercury in the brain, potentially binding with the metal to reduce the induced toxicity, although at different affinities. Our findings call for further studies to investigate the relationship between mercury, selenium, and sulfur, as well as the potential implications in Alzheimer's disease and related dementias.

In vivo quantification of strontium in bone among adults using portable x-ray fluorescence.

BACKGROUND AND OBJECTIVE: Bone strontium (Sr) is a reliable biomarker for studying related bone health outcomes and the effectiveness of Sr supplements in osteoporosis disease treatment. In this study, we evaluated the sensitivity of portable x-ray fluorescence (XRF) technology for in vivo bone Sr quantification among adults. MATERIALS AND METHODS: Sr-doped bone-equivalent phantoms were used for system calibration. Using the portable XRF, we measured bone Sr levels in vivo in mid-tibia bone in 76 adults, 38-95 years of age, living in Indiana, US; we also analyzed bone data of 29 adults, 53-82 years of age, living in Shanghai, China. The same portable XRF device and system settings were used in measuring their mid-tibia bone. We compared bone Sr concentrations by sex, age, and recruitment site. We also used multiple linear regression model to estimate the association of age with bone Sr concentration, adjusting for sex and recruitment site. RESULTS: The uncertainty of in vivo individual measurement increased with higher soft tissue thickness overlying bone, and it ranged from 1.0 ug/g dry bone (ppm) to 2.4 ppm with thickness ranging from 2 to 7 mm, with a measurement time of 5 min. Geometric mean (95% confidence interval (CI)) of the bone Sr concentration was 79.1 (70.1, 89.3) ppm. After adjustment for recruitment site and sex, an increase in five years of age was associated with a 8.9% (95% CI: 2.5%, 15.6%) increase in geometric mean bone Sr concentration. DISCUSSION AND CONCLUSION: Sr concentrations were consistently well above detection limits of the portable XRF, and exhibited an expected increase with age. These data suggest that the portable XRF can be a valuable technology to quantify Sr concentration in bone, and in the study of Sr-related health outcomes among adults, such as bone mineral density (BMD) and bone fracture risk.

Distribution of Pb and Se in mouse brain following subchronic Pb exposure by using synchrotron X-ray fluorescence.

Lead (Pb) is a well-known neurotoxicant and environmental hazard. Recent experimental evidence has linked Pb exposure with neurological deterioration leading to neurodegenerative diseases, such as Alzheimer's disease. To understand brain regional distribution of Pb and its interaction with other metal ions, we used synchrotron micro-x-ray fluorescence technique (µ-XRF) to map the metal distribution pattern and to quantify metal concentrations in mouse brains. Lead-exposed mice received oral gavage of Pb acetate once daily for 4 weeks; the control mice received sodium acetate. Brain tissues were cut into slices and subjected for analysis. Synchrotron µ-XRF scans were run on the PETRA III P06 beamline (DESY). Coarse scans of the entire brain were performed to locate the cortex and hippocampus, after which scans with higher resolution were run in these areas. The results showed that: a) the total Pb intensity in Pb-exposed brain slices was significantly higher than in control brain; b) Pb typically deposited in localized particles of <10 um2 in both the Pb-exposed and control brain slices, with more of these particles in Pb-exposed samples; c) selenium (Se) was significantly correlated with Pb in these particles in the cortex and hippocampus/corpus callosum regions in the Pb-exposed samples, and the molar ratio of the Se and Pb in these particles is close to 1:1. These results indicated that Se may play a crucial role in Pb-induced neurotoxicity. Our findings call for further studies to investigate the relationship between Pb exposure and possible Se detoxification responses, and the implication in the etiology of Alzheimer's disease.

Validation of in vivo toenail measurements of manganese and mercury using a portable X-ray fluorescence device.

BACKGROUND AND OBJECTIVE: Toenail metal concentrations can be used as an effective biomarker for exposure to environmental toxicants. Typically toenail clippings are measured ex vivo using inductively coupled plasma mass spectrometry (ICP-MS). X-ray fluorescence (XRF) toenail metal measurements done on intact toenails in vivo could be used as an alternative to alleviate some of the disadvantages of ICP-MS. In this study, we assessed the ability to use XRF to measure toenail metal concentrations in real-time without having to clip the toenails (i.e., in vivo) in two occupational settings for exposure assessment of manganese and mercury. MATERIALS AND METHODS: The portable XRF method used a 3-min in vivo measurement of toenails prior to clipping and was assessed against ICP-MS measurement of toenail clippings taken immediately after the XRF measurement and work history for a group of welders (n = 16) assessed for manganese exposure and nail salon workers (n = 10) assessed for mercury exposure. RESULTS AND CONCLUSIONS: We identified that in vivo XRF metal measurements were able to discern exposure to manganese in welders and mercury in nail salon workers. We identified significant positive correlations between ICP-MS of clippings and in vivo XRF measures of both toenail manganese (R = 0.59, p = 0.02) and mercury (R = 0.74, p < 0.001), as well as between in vivo XRF toenail manganese and work history among the welders (R = 0.55, p = 0.03). We identified in vivo XRF detection limits to be 0.5 µg/g for mercury and 2.6 µg/g for manganese. Further work should elucidate differences in the timing of exposure using the in vivo XRF method over toenail clippings and modification of measurement time and x-ray setting to further decrease the detection limit. In vivo portable, XRF measurements can be used to effectively measure toenail Mn and Hg in occupational participants in real-time during study visits and at a fraction of the cost.

The association of bone and blood manganese with motor function in Chinese workers.

Manganese (Mn) is an essential element. However, Mn overexposure is associated with motor dysfunction. This cross-sectional study assessed the association between bone Mn (BnMn) and whole blood Mn (BMn) with motor function in 59 Chinese workers. BnMn and BMn were measured using a transportable in vivo neutron activation analysis system and inductively coupled plasma mass spectrometry, respectively. Motor function (manual coordination, postural sway, postural hand tremor, and fine motor function) was assessed using the Coordination Ability Test System (CATSYS) and the Purdue Pegboard. Relationships between Mn biomarkers and motor test scores were analyzed with linear regression models adjusted for age, education, current employment, and current alcohol consumption. BMn was significantly inversely associated with hand tremor intensity (dominant hand (ß=-0.04, 95 % confidence interval (CI):-0.07, -0.01; non-dominant hand ß=-0.05, 95 % CI:-0.08, -0.01) hand tremor center frequency (non-dominant hand ß=-1.61, 95 % CI:-3.03, -0.19) and positively associated with the Purdue Pegboard Assembly Score (ß = 4.58, 95 % CI:1.08, 8.07). BnMn was significantly inversely associated with finger-tapping performance (non-dominant hand ß=-0.02, 95 % CI:-0.04,-0.004), mean sway (eyes closed and foam ß=-0.68, 95 % CI:-1.31,-0.04), and positively associated with hand tremor center frequency (dominant hand, ß = 0.40, 95 % CI:0.002, 0.80). These results suggest BMn is related to better postural hand tremor and fine motor control and BnMn is related to worse motor coordination and postural hand tremor but better (i.e., less) postural sway. The unexpected positive results might be explained by choice of biomarker or confounding by work-related motor activities. Larger, longitudinal studies in this area are recommended.

Childhood and adult socioeconomic position, cumulative lead levels, and pessimism in later life: the VA Normative Aging Study.

Pessimism, a general tendency toward negative expectancies, is a risk factor for depression and also heart disease, stroke, and reduced cancer survival. There is evidence that individuals with higher lead exposure have poorer health. However, low socioeconomic status (SES) is linked with higher lead levels and greater pessimism, and it is unclear whether lead influences psychological functioning independently of other social factors. The authors considered interrelations among childhood and adult SES, lead levels, and psychological functioning in data collected on 412 Boston area men between 1991 and 2002 in a subgroup of the VA Normative Aging Study. Pessimism was measured by using the Life Orientation Test. Cumulative (tibia) lead was measured by x-ray fluorescence. Structural equation modeling was used to quantify the relations as mediated by childhood and adult SES, controlling for age, health behaviors, and health status. An interquartile range increase in lead quartile was associated with a 0.37 increase in pessimism score (P < 0.05). Low childhood and adult SES were related to higher tibia lead levels, and both were also independently associated with higher pessimism. Lead maintained an independent association with pessimism even after childhood and adult SES were considered. Results demonstrate an interrelated role of lead burden and SES over the life course in relation to psychological functioning in older age.

Blood lead levels and cumulative blood lead index (CBLI) as predictors of late neurodevelopment in lead poisoned children.

OBJECTIVE: To find the best lead exposure assessment marker for children. METHODS: We recruited 11 children, calculated a cumulative blood lead index (CBLI) for the children, measured their concurrent BLL, assessed their development, and measured their bone lead level. RESULTS: Nine of 11 children had clinically significant neurodevelopment problems. CBLI and current blood lead level, but not the peak lead level, were significantly or marginally negatively associated with the full-scale IQ score. CONCLUSION: Lead exposure at younger age significantly impacts a child's later neurodevelopment. CBLI may be a better predictor of neurodevelopment than are current or peak blood lead levels.

Evaluation of a portable XRF device for in vivo quantification of lead in bone among a US population.

BACKGROUND: Lead (Pb) concentration in bone is a reliable biomarker for cumulative Pb exposure and studying associated health outcomes. However, the standard K-shell fluorescence (KXRF) bone Pb measurement technology has limitations in large-scale population studies. OBJECTIVE: We compared measurements from a portable XRF device and a KXRF device. METHODS: We measured bone Pb concentrations in vivo using portable XRF and KXRF, each measured at the mid-tibia bone in 71 people, 38-95 years of age (mean ± SD = 63 ± 11 years) living in or near three Indiana communities, US; 10 participants were occupationally exposed. We estimated the correlation between bone Pb concentrations measured by both devices. We also examined the extent to which the detection limit (DL) of the portable XRF was influenced by scan time and overlying soft tissue thickness. Finally, we quantified the associations of estimated bone Pb concentration with age and age with soft tissue thickness. RESULTS: The mean bone Pb concentration measured via portable XRF was 12.3 ± 16.7 mg Pb/kg dry bone. The uncertainty of a 3-minute (N = 60) in vivo portable XRF measurement ranged from 1.8 to 6.3 mg/kg, in the context of soft tissue thickness ranging from 2 to 6 mm. This uncertainty was reduced by a factor of 1.4 with 5-minute measurements (N = 11). Bone Pb measurements via portable XRF and KXRF were significantly correlated: r = 0.48 for all participants, and r = 0.73 among participants with soft tissue thickness < 6 mm (72% of the sample). Bone Pb concentrations were higher among participants who were older or were occupationally exposed to Pb. Soft tissue thickness decreased with age. CONCLUSION: With its ease of use, portability, and comparable sensitivity with conventional KXRF systems, the portable XRF could be a valuable tool for non-invasive quantification of bone Pb in vivo, especially for people with thinner soft tissue.

Whole body potassium as a biomarker for potassium uptake using a mouse model.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

Blood DNA methylation biomarkers of cumulative lead exposure in adults.

BACKGROUND: Lead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels-validated measures of cumulative exposure-require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles-obtainable via Illumina 450K or IlluminaEPIC bead-chip assays. METHODS: We developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity, and sensitivity. FINDINGS: Participants were 73 years old on average (standard deviation, SD = 6), with moderate lead levels of (mean ± SD patella: 27 ± 18 µg/g; tibia:21 ± 13 µg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r = 0.62 patella, r = 0.59 tibia) and had low mean square error (MSE) (MSE = 0.68 patella, MSE = 0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p > 0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74 and 73% for patella and tibia lead levels, respectively, with 70% sensitivity. INTERPRETATION: DNA methylation-based lead biomarkers are novel tools that can be used to reconstruct decades' worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.

Rodent hair is a Poor biomarker for internal manganese exposure.

Hair is used as a biomarker of manganese (Mn) exposure, yet there is limited evidence to support its utility to quantify internal vs external Mn exposure. C57BL/6 J mice and Sprague-Dawley rats were exposed in two blocks of 3 subcutaneous injections every 3 days starting on day 0 or 20. The control group received two blocks of saline (vehicle); Treatment A received the first block as Mn (50 mg/kg MnCl2 tetrahydrate), with the second block as either methylmercury (MeHg at 2.6 or 1.3 mg/kg) for mice or vehicle for rats; and Treatment B received Mn for both blocks. Hair was collected on days 0 and 60 from all treatment groups and Mn quantified by inductively coupled plasma-mass spectrometry (ICP-MS) and total Hg by Direct Mercury Analyzer (DMA). No correlation between internal Mn dose and hair Mn was observed, whereas hair Hg was significantly elevated in MeHg exposed vs non-exposed mice. Whole body Mn content at day 60 was quantified postmortem by neutron activation analysis, which detected significantly elevated Mn for Treatment B in mice and rats. Overall, we find no evidence to support the use of hair as a valid biomarker for internal exposure to Mn at a neurotoxic level.

In vivoneutron activation assembly design for quantification of trace elements using MCNP.

Background: Trace and essential elements both play a crucial role in maintaining normal cellular and organ functions in human, while abnormal exposure to some of them is also potentially related to diseases, e.g.manganism. To study the association between elemental intake and health outcomes, accurate assessment of elemental uptake and storage in the human body is essential.Objective: Technology based on neutron activation analysis can be used forin vivomeasurement of the trace elements given that the measurement system guarantees a low detection limit with an acceptable dose. This study aims to design and optimize a customized and portable deuterium-deuterium neutron generator-based irradiation assembly for the NAA of trace elementsin vivo,using Monte Carlo simulations.Approach: The irradiation assembly includes a moderator, a fast neutron filter, a reflector, and shielding. The human hand phantoms doped with manganese (Mn) and potassium (K) are used to determine the respective elements' system sensitivity and detection limit.Main results: The calculated detection limit is 0.16µg Mn per gram dry bone (ppm) for Mn and 17 ppm for K, with an equivalent dose of 36 mSv to the hand for 10 min irradiation.Significance: This more sensitivein vivoneutron activation analysis system will detect trace elementsin vivo.

Characterization of bone aluminum, a potential biomarker of cumulative exposure, within an occupational population from Zunyi, China.

OBJECTIVES: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs). METHODS: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al. RESULTS: Median (interquartile range (IQR)) Al measurements were: 15 µg/g dry bone (IQR = 28) for bone Al; 34.9 µg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (ß = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (ß = 0.98, 95% CI: -0.14, 2.1; ß = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant. CONCLUSIONS: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.

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.