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Objectives: We assessed the extent of exposure to lead, cadmium, and mercury in the New York City (NYC) adult population., Methods: We measured blood metal concentrations in a representative sample of 1,811 NYC residents as part of the NYC Health and Nutrition Examination Survey, 2004., Results: The geometric mean blood mercury concentration was 2.73 microg/L [95% confidence interval (CI), 2.58-2.89]; blood lead concentration was 1.79 microg/dL (95% CI, 1.73-1.86); and blood cadmium concentration was 0.77 microg/L (95% CI, 0.75-0.80). Mercury levels were more than three times that of national levels. An estimated 24.8% (95% CI, 22.2-27.7%) of the NYC adult population had blood mercury concentration at or above the 5 microg/L New York State reportable level. Across racial/ethnic groups, the NYC Asian population, and the foreign-born Chinese in particular, had the highest concentrations of all three metals. Mercury levels were elevated 39% in the highest relative to the lowest income group (95% CI, 21-58%). Blood mercury concentrations in adults who reported consuming fish or shellfish 20 times or more in the last 30 days were 3.7 times the levels in those who reported no consumption (95% CI, 3.0-4.6); frequency of consumption explained some of the elevation in Asians and other subgroups., Conclusions: Higher than national blood mercury exposure in NYC adults indicates a need to educate New Yorkers about how to choose fish and seafood to maximize health benefits while minimizing potential risks from exposure to mercury. Local biomonitoring can provide valuable information about environmental exposures.

During June-August 2004, blood lead (BPb) levels and various hematological parameters were evaluated in children aged 5-9 years old at ten primary schools located in eight neighborhoods in Cartagena, Colombia. The schools selected for this study are attended mainly by children from families of low income. A total of 189 subjects participated in the survey. The arithmetic mean+/-standard error BPb level was 5.49+/-0.23 microg/dL (range<1.0-21.0 microg/dL). The geometric mean was 4.74 microg/dL (95% CI: 4.29-5.18). A proportion of the children (7.4%) had BPb levels above the US Centers for Disease Control and Prevention's threshold of concern (10 microg Pb/dL). BPb levels were correlated weakly, but significantly and positively, with red blood cell count (RBC), and negatively with child body size, age, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). BPb levels did not differ significantly between boys and girls but significant differences were observed between neighborhoods (P<0.001). Activities such as metal melting-related processes and fishing net sinker production are the main sources of Pb exposure in Cartagena.

Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.

The tetracysteine metal coordination site of the rubredoxins from Clostridium pasteurianum (Cp) and Pyrococcus furiosus (Pf) are shown to stably bind the inorganic Ge(IV) ion. This is the first characterized coordination complex of tetravalent germanium with a biological macromolecule. Zn(II), Ga(III) and Ge(IV) substitution yields differential NMR chemical shifts for the 1H and 15N amide resonances throughout much of the protein structure. The differential shifts for the six backbone amides that hydrogen bond to the metal-coordinated sulfurs indicate that the pseudo 2-fold symmetry of the active site is more closely maintained in the hyperthermophile Pf rubredoxin than in its mesophile Cp homolog. These three metal substitutions form an isoelectronic series of small diamagnetic proteins for which reference structures are known to 1A resolution. These series provide a promising system to analyze theoretical predictions of the effects of differential charge distribution on chemical shifts from both proximal and long range interactions.

Lead accumulates in bone over many years or decades. Accordingly, the study of lead in bone is important in determining the fate of ingested lead, the potential for remobilization, and for the application of bone lead measurements as a biomarker of lead exposure. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to measure the spatial distribution of lead in bone on the micrometer scale. In general, LA-ICP-MS studies are somewhat limited by the lack of matrix-matched standards and/or reference materials for calibration and validation purposes. Here we describe the application of pressed pellets prepared from New York State Department of Health candidate Reference Materials for Lead in Bone (levels 1 through 4), to provide a linear calibration for (208)Pb/(43)Ca in the concentration range <1 to 30 μg g(-1). The limit of detection was estimated as 0.2 μg g(-1). The measured lead values for pelletized NIST SRM 1486 Bone Meal and SRM 1400 Bone Ash were in good agreement with certified reference values. Using this approach, we quantitatively measured the spatial distribution of lead in a cross-section of goat metacarpal from a lead-dosed animal. The lead content was spatially variable in the range of 2 to 30 μg g(-1) with a complex distribution. In some sections, lead appeared to be enriched in the center of the bone relative to peripheral areas, indicating preferential accumulation in trabecular (spongy) rather than cortical bone. In addition, there were discrete areas of lead enrichment, or hot spots, of 100 to 200 μm in width.

Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health Organization define a BPb of 10 microg/dL (0.48 micromol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 microg/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth.

Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects.

A number of studies have found that increasing lead exposure is associated with increases in blood pressure in humans. Studies with animals suggest that lead-induced increases in vascular resistance account for these increases in blood pressure. The present study assessed cardiovascular functioning at rest and in response to acute stress for 9(1/2) year old children (N=122) having relatively low prenatal (cord) blood lead levels (M=1.98 microg/dL, SD=1.75) and low postnatal (early childhood) blood lead levels (M=4.62 microg/dL, SD=2.51). Higher cord blood levels were associated with higher baseline systolic blood pressure (SBP), and higher early childhood lead levels were associated with greater total peripheral (vascular) resistance (TPR) responses to acute stress. In addition, a negative association between blood lead levels and stroke volume (SV) suggests that lead-induced increases in vascular resistance were sufficient to produce cardiac afterload, a situation arising when blood pressure in the aorta makes it difficult for the left ventricle to eject blood. These effects were not mediated by differences in task performance or emotional responses to the acute stress tasks. Finally, these effects were significant for lead levels considered low, notably, below the 10 microg/dL threshold currently adopted by the CDC for deleterious effects.

BALB/c mice were exposed to 0.1 ppm lead acetate in the drinking water from postnatal day (PND) 1 for 6 weeks. Until PND21, lead exposure was from mother's milk; thereafter, it was directly from the drinking water. The blood lead levels were the highest in pups before weaning (59.5+/-0.9 microg/dL) and significantly lower between PND21 and PND42 (20.3+/-4.7 microg/dL). At PND42, lead-exposed male mice were tested for fertility, sperm DNA, and macrophage number. Mating of lead-treated males with non-treated females confirmed the reduction of fertility in the exposed males. Flow cytometric studies of testicular preparations indicated that the sperm count was not different between lead-exposed and control males; however, the lead-treated mice had a significant increase in the number of testicular cells having a < 1n amount of DNA, which coincided with a decrease in the number of testicular cells with a 2n and 4n amount of DNA. The number of testicular macrophages also was decreased in lead-exposed males, which could reflect altered levels of CSF-1 or response to CSF-1, as previously reported [Kowolenko, M., Tracy, L., Lawrence, D.A., 1989. Lead-induced alterations of in vitro bone marrow cell responses to colony stimulating factor-1. J. Leukoc. Biol. 45, 198-206]. Our study showed that exposure to 0.1 ppm of lead during the neonatal and adolescent period is sufficient to reduce fertility in adult male mice; however, it did not affect sperm count on PND42. The presence of an increased number of apoptotic (< 1n amount of DNA) testicular cells may be diagnostic of defective sperm function. Thus, an administered dose of 0.1 ppm via drinking water ingestion by neonatal male BALB/c mice sufficient to produce PbB of 20-60 mg/dL compromised reproductive function in these mice as adults.

Objective: We sought to compare associations of patella lead, which may represent a unique cumulative and bioavailable lead pool, with other lead measures in models of renal function., Methods: Renal function measures included blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-beta-D-glucosaminidase (NAG) and retinol-binding protein., Results: In 652 lead workers, mean (SD) blood, patella, and tibia lead were 30.9 (16.7) microg/dL, 75.1 (101.1) and 33.6 (43.4) microg Pb/g bone mineral, respectively, and were correlated (Spearman's r = 0.51-0.74). Patella lead was associated (P < 0.05) with NAG in all lead workers. In models of effect modification by age, higher patella lead also was associated with higher serum creatinine in older participants. Similar associations were observed for blood and tibia lead., Conclusions: Associations between patella lead and adverse renal outcomes were not unique; this may be due, in part, to high correlations among the lead biomarkers in this study.

Recent research suggests that both uric acid and lead may be nephrotoxic at lower levels than previously recognized. We analyzed data from 803 current and former lead workers to determine whether lead biomarkers were associated with uric acid and whether previously reported associations between lead dose and renal outcomes were altered after adjustment for uric acid. Outcomes included uric acid, blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-ss-d-glucosaminidase (NAG) and retinol-binding protein. Mean (+/- SD) uric acid, tibia lead, and blood lead levels were 4.8 +/- 1.2 mg/dL, 37.2 +/- 40.4 microg/g bone mineral, and 32.0 +/- 15.0 microg/dL, respectively. None of the lead measures (tibia, blood, and dimercaptosuccinic-acid-chelatable lead) was associated with uric acid, after adjustment for age, sex, body mass index, and alcohol use. However, when we examined effect modification by age on these relations, both blood and tibia lead were significantly associated (ss = 0.0111, p < 0.01 and ss = 0.0036, p = 0.04, respectively) in participants in the oldest age tertile. These associations decreased after adjustment for blood pressure and renal function, although blood lead remained significantly associated with uric acid (ss = 0.0156, p = 0.01) when the population was restricted to the oldest tertile of workers with serum creatinine greater than the median (0.86 mg/dL). Next, in models of renal function in all workers, uric acid was significantly (p < 0.05) associated with all renal outcomes except NAG. Finally, in the oldest tertile of workers, associations between lead dose and NAG were unchanged, but fewer associations between the lead biomarkers and the clinical renal outcomes remained significant (p less than or equal to 0.05) after adjustment for uric acid. In conclusion, our data suggest that older workers comprise a susceptible population for increased uric acid due to lead. Uric acid may be one, but not the only, mechanism for lead-related nephrotoxicity.

A cross-sectional analysis was performed to evaluate associations of polymorphisms in the vitamin D receptor (VDR), delta-aminolevulinic acid dehydratase (ALAD), and endothelial nitric oxide synthase (eNOS) genes with patella lead concentrations in 652 lead workers in the Republic of Korea. There was a wide range of patella lead (from below detection limit to 946 microg Pb/g bone mineral), with a mean (standard deviation) of 75.2 (101.0). There were no associations of ALAD or eNOS genotypes with patella lead, but workers with the VDR B allele had significantly (P value < 0.05) higher patella lead (on average, 25% or approximately 6.6 microg Pb/g bone mineral) than lead workers with the VDR bb genotype. There was evidence that the relation between age and patella lead was modified by both the VDR and eNOS genotypes.

We analyzed data from 798 lead workers to determine whether polymorphisms in the genes encoding delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR) were associated with or modified relations of lead exposure and dose measures with renal outcomes. Lead exposure was assessed with job duration, blood lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and tibia lead. Renal function was assessed with blood urea nitrogen (BUN), serum creatinine, measured creatinine clearance, calculated creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG), and retinol-binding protein. Mean (+/- SD) tibia lead, blood lead, and DMSA-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0 +/- 15.0 microg/dL, and 767.8 +/- 862.1 microg/g creatinine, respectively. After adjustment, participants with the ALAD(2) allele had lower mean serum creatinine and higher calculated creatinine clearance. We observed effect modification by ALAD on associations between blood lead and/or DMSA-chelatable lead and three renal outcomes. Among those with the ALAD(1-2) genotype, higher lead measures were associated with lower BUN and serum creatinine and higher calculated creatinine clearance. Participants with the eNOS variant allele were found to have higher measured creatinine clearance and BUN. In participants with the Asp allele, longer duration working with lead was associated with higher serum creatinine and lower calculated creatinine clearance and NAG; all were significantly different from relations in those with the Glu/Glu genotype except NAG (p = 0.08). No significant differences were seen in renal outcomes by VDR genotype, nor was consistent effect modification observed. The ALAD findings could be explained by lead-induced hyperfiltration.

To determine the influences of maternal diet and nutrition during pregnancy on the blood lead level of neonates, we conducted a study of mother-infant pairs from lower socioeconomic circumstances living in Albany County, New York. Maternal blood lead (MBPb), anthropometry, and diet were assessed in each trimester. Neonates' blood lead (NBPb) levels were low (geometric mean = 1.58 micro g/dL), and none had elevated blood lead. More than 50% of the mothers had intakes below the recommended dietary allowances for zinc, calcium, iron, vitamin D, and kilocalories. As expected, MBPb was strongly and positively related to NBPb. Among the anthropometric measures of maternal nutritional status, variables measuring gain in weight and arm circumference were negatively related to NBPb. In multivariable models reflecting different analytic strageties and including MBPb, anthropometry, and sociodemographic characteristics, dietary intakes of iron and vitamin D were negatively related to NBPb. The effect of zinc varied substantially depending on model covariates. Effects of dietary constituents are difficult to distinguish, given the intercorrelated nature of nutrients in the diet. Nevertheless, the influences of maternal anthropometric variables, iron, and vitamin D on neonatal lead levels are clear in our analyses.

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

The aim of this study was to validate 109Cd-based K-shell x-ray fluorescence measurements against atomic absorption spectrometry (AAS) measurements of core and surface tibia lead. The lead content of nine adult human cadaver tibiae was measured using 109Cd-based K-shell x-ray fluorescence (XRF) spectrometry and the results compared to measurements obtained using electrothermal atomization atomic absorption spectrometry following acid digestion. Each tibia was divided into nine cross-sectional segments, which were further separated into tibia core and surface samples for the AAS analytical measurements. Proximal-distal variability in tibia lead concentration as determined by AAS was previously described for both surface and core segments and was found to decrease towards the ends of the tibia, in contrast to XRF in which lead was found to increase towards the tibia ends. The effect of this contrasting behaviour on the agreement between XRF and AAS measurements was examined. Lead concentrations determined by AAS ranged from 3 to 19 microg of lead per gram of dry weight bone (microg g(-1)) for tibia core and from 5 to 32 microg g(-1) for tibia surface. Lead concentrations determined by XRF ranged from 2 to 35 microg g(-1) dry weight. No statistically significant difference was found between mean XRF-measured concentrations and mean surface lead concentrations measured by AAS, but XRF significantly overestimated tibia core lead concentrations by between 5 and 8 microg g(-1).