Lead uptake into calcified and keratinized compartments of horns from a convenience sample of lead-dosed goats.

Hair and/or nail analyses are sometimes used in biomonitoring studies due to the convenience of sample collection, storage, and transport, as well as the potential to assess past exposures to toxic metals, such as lead (Pb). However, the validity of Pb measurements in these keratinized matrices as biomarkers of absorbed dose remains unclear. The aim of this study was to examine the uptake of Pb into horns harvested postmortem from 11 goats that received a cumulative oral dose of up to 151 g Pb acetate over a period of 1-11 years as part of a long-term blood Pb proficiency testing program. Uptake of Pb into keratinized horn was compared to the corresponding underlying bony horn core, which, as part of the bone compartment, provided a measure of absorbed Pb dose. Two complementary analytical techniques were used to assess Pb: X-Ray Fluorescence (XRF) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Detectable amounts of Pb were found in all keratinized horn samples (0.45-6.6 µg/g) and in all but one bony core sample (1.4-68 µg/g). In both bony core and keratinized horn samples, Pb accumulation increased with dose over a low-to-moderate cumulative-dose interval, consistent with previous observations, but plateaued at higher doses. Significant associations were observed between Pb in keratinized horn and bony core samples particularly with XRF measurements, which represent the surface bone compartment. These findings provide evidence that Pb is excreted in keratinized tissues but reflects only a small fraction of the absorbed Pb dose, likely transferred from underlying bone tissue.

Bone lead associations with blood lead, kidney function and blood pressure among US, lead-exposed workers in a surveillance programme.

OBJECTIVES: Bone lead and past blood lead levels may be more strongly associated with current health effects than current blood lead, representing recent exposure. We examined whether current bone lead was correlated with maximum past blood lead and compared how three lead measures predicted current blood pressure (BP) and kidney function among workers with past occupational lead exposure. METHODS: Adult men in a lead surveillance programme residing near New York City were enrolled. Current bone and blood lead, BP and estimated glomerular filtration rate (eGFR) were measured. Maximum past blood lead was obtained from surveillance data. Regression models were used to determine associations of health with different lead measures. RESULTS: Among 211 participants, median (IQR) bone, maximum past blood and current blood leads were 13.8 (9.4-19.5) µg lead per bone mineral gram, 29.0 (14.0-38.0) µg/dL and 2.5 (1.5-4.4) µg/dL, respectively. Maximum past and current blood lead were significantly associated with current bone lead in adjusted analyses (both p<0.0001), with associations driven by high blood lead. Bone lead was associated with increased continuous systolic BP (coefficient=0.36; 95% CI 0.05 to 0.67; p=0.02); categorical analyses indicated this was driven by the top two bone lead quartiles. Bone lead was non-significantly associated with decreased (worse) eGFR (coefficient=-0.15; 95% CI -0.36 to 0.07; p=0.18). CONCLUSIONS: Bone lead was significantly associated with past maximum and current blood lead. The association between bone and current blood lead was possibly driven by bone lead resorption into blood. Bone lead, but not past or current blood lead, was associated with elevated systolic BP.

A Western Diet Pattern Is Associated with Higher Concentrations of Blood and Bone Lead among Middle-Aged and Elderly Men.

Background: Little is known about the effects of overall dietary pattern on lead concentration.Objective: We examined the association of overall dietary patterns, derived from a semiquantitative food frequency questionnaire, with bone and blood lead concentrations.Methods: These longitudinal analyses included mostly non-Hispanic white, middle-aged-to-elderly men from the Veterans Affairs Normative Aging Study. Long-term lead exposures were measured as tibia and patella lead concentrations by using K-shell-X-ray fluorescence. Short-term lead exposures were measured as blood lead concentrations by using graphite furnace atomic absorption spectroscopy. Dietary pattern scores were derived by using factor analysis. Linear mixed-effects models were utilized to predict blood lead concentrations among 983 men, aged 44-92 y at baseline, with a total of 3273 observations (during 1987-2008). We constructed linear regression models to determine the relations between dietary patterns and bone lead concentrations among 649 participants with an age range of 49-93 y.Results: Two major dietary patterns were identified: a prudent dietary pattern, characterized by high intakes of fruit, legumes, vegetables, whole grains, poultry, and seafood; and a Western dietary pattern, characterized by high intakes of processed meat, red meat, refined grains, high-fat dairy products, French fries, butter, and eggs. After adjusting for age, smoking status, body mass index, total energy intake, education, occupation, neighborhood-based education and income level, men in the highest tertile of the Western pattern score (compared with the lowest) had 0.91 µg/dL (95% CI: 0.41, 1.42 µg/dL) higher blood lead, 5.96 µg/g (95% CI: 1.76, 10.16 µg/g) higher patella lead, and 3.83 µg/g (95% CI: 0.97, 6.70 µg/g) higher tibia lead. No significant association was detected with the prudent dietary pattern in the adjusted model.Conclusions: These findings suggest that the Western diet is associated with a greater lead body burden among the middle-aged-to-elderly men. More studies are needed to examine the underlying mechanisms by which dietary patterns are associated with lead concentrations.

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.

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.

Association between Bone Lead Concentration and Aggression in Youth from a Sub-Cohort of the Birth to Twenty Cohort.

BACKGROUND: An association between blood-lead levels and aggression has been demonstrated in children and adolescent youth in South Africa. However, there are limited studies that have assessed aggression as an outcome for cumulative lead exposure using bone lead concentration. This study aims to assess the association between bone lead concentration and aggressive behaviour among a sample of youth in South Africa. METHODS: Bone lead in 100 participants (53 males and 47 females) recruited and followed in the Birth to Twenty (BT20) Cohort were measured using 109 Cd-based, K-shell X-ray fluorescence (KXRF). The Buss-Perry Aggression questionnaire was used to measure aggressive behaviour. Linear regression models were fitted to determine the association between aggression score for physical, verbal, anger and hostility and bone lead, adjusting for known confounders. RESULTS: A one-microgram-per-gram increase in bone lead was found to increase the score for all four scales of aggression, but significantly only for anger (ß = 0.2 [95% CI 0.04-0.370]). Psychosocial factors such as a history of family violence and exposure to neighbourhood crime were significant predictors for aggression. CONCLUSIONS: The study provides a preliminary overview of the relationship between cumulative lead exposure and behavioural problems such as aggression. A larger sample, across exposed communities, may prove more definitive in further investigating the association between these two important public health factors and to maximize generalizability.

Early lead exposure and childhood adiposity in Mexico city.

BACKGROUND: Prenatal and early childhood lead exposures have been associated with reduced weight in infants and young children, while studies that have examined such associations in children during peripubescence are rare. OBJECTIVES: We investigated the associations of prenatal and early-life exposure to lead with indices of adiposity in peripubertal children living in Mexico City. METHODS: Maternal bone lead (as a proxy for cumulative fetal exposure) was assessed at 1 month postpartum. Blood samples were obtained from children annually from 1 to 4 years. Multivariable linear regression models were used to examine the association between each lead biomarker and BMI z-score, waist circumference, sum of skinfolds and body fat percentage in 248 children aged 8-16 years. RESULTS: After adjusting for covariates, maternal patella lead was associated with lower child BMI z-score (ß = -0.02, 95% CI: 0.03, -0.01, p = 0.004), waist circumference (ß = -0.12 cm, 95% CI: 0.22, -0.03, p = 0.01), sum of skinfolds (ß = -0.29 mm, 95% CI: 0.50, -0.08, p = 0.007) and body fat percentage (ß = -0.09%, 95% CI: 0.17, -0.01, p = 0.03). No significant associations were detected from the postnatal exposure period. CONCLUSIONS: We observed a significant and inverse association of prenatal lead exposure with body composition in Mexican children, suggesting the potential role of early lead exposure in the fetal programming of child growth. Further research on the biological mechanisms underlying these associations is needed.

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.

Early lead exposure and pubertal development in a Mexico City population.

BACKGROUND: Previous studies have examined the association between blood lead levels and pubertal timing in adolescent girls; however, the evidence is lacking on the role of lead exposure during sensitive developmental periods on sexual maturation. OBJECTIVES: To examine the association of prenatal and early childhood lead exposure with pubertal stages among 264 boys and 283 girls aged 9.8-18.0 years in Mexico City. METHODS: We measured maternal bone lead (a proxy for cumulative fetal exposure to lead from maternal bone stores mobilized during pregnancy) at 1 month postpartum. Blood lead was measured annually from 1 to 4 years. Pubertal stage was assessed by a pediatrician. We examined the association between lead and pubertal stages of breast, pubic hair and genitalia using ordinal regression. Age at menarche was evaluated using Cox proportional-hazard models. RESULTS: Multivariate models showed that maternal patella lead and early childhood blood lead were inversely associated with breast growth (patella OR = 0.72, 95% CI: 0.51-1.00; blood OR = 0.70, 95% CI: 0.53-0.93) in girls. Girls with maternal patella lead in the 3rd tertile and child blood lead in the 2nd tertile had a later age at menarche compared with girls in the 1st tertile (patella HR = 0.60, 95% CI: 0.41-0.88; blood HR = 0.65, 95% CI 0.46-0.91). Additionally, early childhood blood lead was negatively associated with pubic hair growth (OR = 0.68, 95% CI: 0.51-0.90) in girls. No associations were found in boys. CONCLUSIONS: These data suggest that higher prenatal and early childhood exposure to lead may be associated with delayed pubertal development in girls but not boys. Our findings are consistent with previous analyses and reinforce the reproductive effects of lead for girls.

Effect of Dietary Sodium and Potassium Intake on the Mobilization of Bone Lead among Middle-Aged and Older Men: The Veterans Affairs Normative Aging Study.

Bone is a major storage site as well as an endogenous source of lead in the human body. Dietary sodium and potassium intake may play a role in the mobilization of lead from bone to the circulation. We examined whether association between bone lead and urinary lead, a marker of mobilized lead in plasma, was modified by dietary intake of sodium and potassium among 318 men, aged 48-93 years, in the Veterans Affairs (VA) Normative Aging Study. Dietary sodium and potassium were assessed by flame photometry using 24-h urine samples, and a sodium-to-potassium ratio was calculated from the resulting measures. Patella and tibia bone lead concentrations were measured by K-shell-x-ray fluorescence. Urinary lead was measured by inductively coupled plasma mass spectroscopy in 24-h urine samples. Linear regression models were used to regress creatinine clearance-corrected urinary lead on bone lead, testing multiplicative interactions with tertiles of sodium, potassium, and sodium-to-potassium ratio, separately. After adjustment for age, body mass index, smoking, vitamin C intake, calcium, and total energy intake, participants in the highest tertile of sodium-to-potassium ratio showed 28.1% (95% CI: 12.5%, 45.9%) greater urinary lead per doubling increase in patella lead, whereas those in the second and lowest tertiles had 13.8% (95% CI: -1.7%, 31.7%) and 5.5% (95% CI: -8.0%, 21.0%) greater urinary lead, respectively (p-for-interaction = 0.04). No statistically significant effect modification by either sodium or potassium intake alone was observed. These findings suggest that relatively high intake of sodium relative to potassium may play an important role in the mobilization of lead from bone into the circulation.

Bone lead levels in an environmentally exposed elderly population in shanghai, China.

This study looked at measurements of lead (Pb) in a pilot population of environmentally exposed elderly residents of Shanghai, China and presented the first set of bone Pb data on an elderly Chinese population. We found that with environmental exposures in this population using K-shell x-ray fluorescence (KXRF) bone Pb measurements 40% of the individuals had bone Pb levels above the nominal detection limit with an average bone lead level of 4.9 ±â€¯3.6 µg/g. This bone lead level is lower than comparable values from previous studies of community dwelling adults in US cities. This population had a slightly higher geometric mean blood Pb of 2.6 µg/dL than the adult US population. The main conclusion of this data is that in Shanghai there is environmental exposure to Pb, measured through blood and bone, which should be further investigated to assess the health impact of this exposure.

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

INTRODUCTION: Olfactory 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. METHODS: Olfactory 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). RESULTS: The 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 15 µg/g tibia lead: ß=-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 ß=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 15 µg/g tibia lead: ß=-1.25; 95% CI: -2.64, 0.14; p=0.08) while the HFE term dropped 15% (ß=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 15 µg/g tibia lead ß=-1.39; 95% CI: -3.00, 0.22; p=0.09). CONCLUSION: Cumulative 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.

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women.

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76 ± 8, body mass index (BMI): 26.74 ± 4.26 kg/m(2)) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using (109)Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 µm in-plane resolution, 2.3 ± 0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (-0.972 (-1.882, -0.061) per 100 µg Pb/g of bone mineral) and integral volumetric BMD (-3.05 (-6.05, -0.05) per µg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (-26.83 (-50.37, -3.29)) and trabecular number (-0.08 (-0.14, -0.02)), per 100 µg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD.

A Temporal Association between Accumulated Petrol (Gasoline) Lead Emissions and Motor Neuron Disease in Australia.

BACKGROUND: The age standardised death rate from motor neuron disease (MND) has increased from 1.29 to 2.74 per 100,000, an increase of 112.4% between 1959 and 2013. It is clear that genetics could not have played a causal role in the increased rate of MND deaths over such a short time span. We postulate that environmental factors are responsible for this rate increase. We focus on lead additives in Australian petrol as a possible contributing environmental factor. METHODS: The associations between historical petrol lead emissions and MND death trends in Australia between 1962 and 2013 were examined using linear regressions. RESULTS: Regression results indicate best fit correlations between a 20 year lag of petrol lead emissions and age-standardised female death rate (R² = 0.86, p = 4.88 × 10(-23)), male age standardised death rate (R² = 0.86, p = 9.4 × 10(-23)) and percent all cause death attributed to MND (R² = 0.98, p = 2.6 × 10(-44)). CONCLUSION: Legacy petrol lead emissions are associated with increased MND death trends in Australia. Further examination of the 20 year lag between exposure to petrol lead and the onset of MND is warranted.

Occupational health management in the lead industry: the korean experience.

In 1967, the problem of occupational lead exposure came to public attention in Korea. Since then, regular progress has been made in lowering workplace lead exposures, instituting new workplace controls, and implementing health examinations of exposed workers. Past serious lead poisoning episodes made it possible to introduce biological monitoring programs on a voluntary basis in high-lead-exposure facilities in Korea. Industry-specific occupational health services for lead workers in Korea during the last 22 years can be categorized into three phases. During the first phase (1988-1993), efforts were directed at increasing awareness among workers about the hazards of lead exposure, biological monitoring of blood zinc protoporphyrin began, and a respiratory protection program was introduced. During the second phase (1994-1997), a computerized health management system for lead workers was developed, blood-lead measurement was added to biologic monitoring, and engineering controls were introduced in the workplace to lower air-lead levels to comply with air-lead regulations. Finally, during the third phase (1998-present), a new biomarker, bone-lead measurement by X-ray fluorescence, was introduced. Bone-lead measurement proved to be useful for assessing body burden and to demonstrate past lead exposure in retired workers. Occupational health service practice for lead workers, including the industry-specific group occupational health system, has brought considerable success in the prevention of lead poisoning and in reducing the lead burden in Korean lead workers during the last several decades. The successful achievement of prevention of lead poisoning in Korea was a result of the combined efforts of lead workers, employers, relevant government agencies, and academic institutes.

Cumulative lead exposure and tooth loss in men: the normative aging study.

BACKGROUND: Individuals previously exposed to lead remain at risk because of endogenous release of lead stored in their skeletal compartments. However, it is not known if long-term cumulative lead exposure is a risk factor for tooth loss. OBJECTIVES: We examined the association of bone lead concentrations with loss of natural teeth. METHODS: We examined 333 men enrolled in the Veterans Affairs Normative Aging Study. We used a validated K-shell X-ray fluorescence (KXRF) method to measure lead concentrations in the tibial midshaft and patella. A dentist recorded the number of teeth remaining, and tooth loss was categorized as 0, 1-8 or > or = 9 missing teeth. We used proportional odds models to estimate the association of bone lead biomarkers with tooth loss, adjusting for age, smoking, diabetes, and other putative confounders. RESULTS: Participants with > or = 9 missing teeth had significantly higher bone lead concentrations than those who had not experienced tooth loss. In multivariable-adjusted analyses, men in the highest tertile of tibia lead (> 23 microg/g) and patella lead (> 36 microg/g) had approximately three times the odds of having experienced an elevated degree of tooth loss (> or = 9 vs. 0-8 missing teeth or > or = 1 vs. 0 missing teeth) as those in the lowest tertile [prevalence odds ratio (OR) = 3.03; 95% confidence interval (CI), 1.60-5.76 and OR = 2.41; 95% CI, 1.30-4.49, respectively]. Associations between bone lead biomarkers and tooth loss were similar in magnitude to the increased odds observed in participants who were current smokers. CONCLUSION: Long-term cumulative lead exposure is associated with increased odds of tooth loss.

A proton magnetic resonance spectroscopy study of the chronic lead effect on the Basal ganglion and frontal and occipital lobes in middle-age adults.

BACKGROUND: Lead is known to be a health hazard to the human brain and nervous system based on data from epidemiologic studies. However, few studies have examined the mechanism or biochemical changes caused by lead in the human brain, although recently some have used magnetic resonance spectroscopy (MRS) to test brain metabolism in vivo. OBJECTIVES: In this study, we used 3-T MRS to investigate brain metabolism in workers chronically exposed to lead and matched nonexposed controls. METHODS: Twenty-two workers at a lead paint factory served as chronically exposed subjects of this study. These workers did not have any clinical syndromes. Eighteen age- and sex-matched nonexposed healthy volunteers served as controls. We measured blood and bone lead and used a 3-T MRS to measure their levels of brain N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr). A structural questionnaire was used to collect demographic, work, and health histories and information about their life habits. RESULTS: All the MRS measures were lower in the lead-exposed group. Increased blood and bone lead levels correlated with declines in Cho:tCr ratios, especially in the occipital lobe, where changes in all gray, subcortical, and white matter were significant. Increases in blood and patella lead in every layer of the frontal lobe correlated with significant decreases in NAA:tCr ratios. One of the strongest regression coefficients was -0.023 (SE = 0.005, p < 0.001), which was found in the NAA:tCr ratio of frontal gray matter. DISCUSSION: We conclude that chronic exposure to lead might upset brain metabolism, especially NAA:tCr and Cho:tCr ratios. Brain NAA and Cho are negatively correlated to blood and bone lead levels, suggesting that lead induces neuronal and axonal damage or loss. The most significant changes occurred in frontal and occipital lobes, areas in which previous neurobehavioral studies have shown memory and visual performance to be adversely affected by lead toxicity.

Cumulative exposure to lead in relation to cognitive function in older women.

BACKGROUND: Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women. OBJECTIVE: We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women. METHODS: Patella and tibia bone lead--measures of cumulative exposure over many years--and blood lead, a measure of recent exposure, were assessed in 587 women 47-74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews. RESULTS: Mean +/- SD lead levels in tibia, patella, and blood were 10.5 +/- 9.7 microg/g bone, 12.6 +/- 11.6 microg/g bone, and 2.9 +/- 1.9 microg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: -0.099 to -0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age. CONCLUSIONS: These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women's cognition in older age.

Influence of prenatal lead exposure on genomic methylation of cord blood DNA.

BACKGROUND: Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility. OBJECTIVE: This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples. METHODS: We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source (109)Cd K-shell X-ray fluorescence instrument. RESULTS: We found an inverse dose-response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (beta= -0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation. CONCLUSIONS: Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.