Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

BACKGROUND: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. METHODS: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. RESULTS: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m2, 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. CONCLUSIONS: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185.

Cottage industry as a source of high exposure to lead: A biomonitoring study among people involved in manufacturing cookware from scrap metal.

In low-income countries, a widespread but poorly studied type of cottage industry consists of melting scrap metal for making cookware. We assessed the exposure to lead (Pb) among artisanal workers, and their families, involved in manufacturing cookware from scrap metal. In a cross-sectional survey, we compared artisanal cookware manufacturing foundries with carpentry workshops (negative controls) and car battery repair workshops (positive controls), all located in residential areas, in Lubumbashi (DR Congo). We collected surface dust in the workspaces, and blood and urine samples among workers, as well as residents living in the cookware workshops. Trace elements were quantified in the samples by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In surface dust, median Pb concentrations were higher in cookware foundries (347 mg/kg) than in carpentries (234 mg/kg) but lower than in battery repair workshops (22,000 mg/kg). In workers making the cookware (n = 24), geometric mean (GM) Pb blood cencentration was 118 µg/L [interquartile range (IQR) 78.4-204], i.e. nearly twice as high as among carpenters [60.2 µg/L (44.4-84.7), n = 33], and half the concentration of battery repair workers [255 µg/L (197-362), n = 23]. Resident children from the cookware foundries, had higher urinary Pb [6.2 µg/g creatinine (2.3-19.3), n = 6] than adults [2.3 (2.2-2.5), n = 3]. Our investigation confirms the high Pb hazard linked to car battery repair and reveals a high exposure to Pb among artisanal cookware manufacturers and their families, especially children, in residential areas of a city in a low-income country.

Exposure to a mixture of metal(loid)s and sleep quality in pregnant women during early pregnancy: A cross-sectional study.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

Identification of the regulatory network and potential markers for type 2 diabetes mellitus related to internal exposure to metals in Chinese adults.

People intake metals from their environment. This study investigated type 2 diabetes mellitus (T2DM) related to internal exposure to metals and attempted to identify possible biomarkers. A total of 734 Chinese adults were enrolled, and urinary levels of ten metals were measured. Multinomial logistic regression model was used to assess the association between metals and impaired fasting glucose (IFG) and T2DM. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction were used to explore the pathogenesis of T2DM related to metals. After adjustment, lead (Pb) was positively associated with IFG (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.06-1.61) and T2DM (OR 1.41, 95% CI 1.01-1.98), but cobalt was negatively associated with IFG (OR 0.57, 95% CI 0.34-0.95). Transcriptome analysis showed 69 target genes involved in the Pb-target network of T2DM. GO enrichment indicated that the target genes are enriched mainly in the biological process category. KEGG enrichment indicated that Pb exposure leads to non-alcoholic fatty liver disease, lipid and atherosclerosis, and insulin resistance. Moreover, there is alteration of four key pathways, and six algorithms were used to identify 12 possible genes in T2DM related to Pb. SOD2 and ICAM1 show strong similarity in expression, suggesting a functional correlation between these key genes. This study reveals that SOD2 and ICAM1 may be potential targets of Pb exposure-induced T2DM and provides novel insight into the biological effects and underlying mechanism of T2DM related to internal exposure to metals in the Chinese population.

Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals.

Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p < 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

Global DNA (LINE-1) methylation is associated with lead exposure and certain job tasks performed by electronic waste workers.

OBJECTIVE: This study assessed the associations between blood and urine levels of toxic metals; cadmium (Cd) and lead (Pb), and methylation levels of the LINE-1 gene among e-waste and control populations in Ghana. METHODS: The study enrolled 100 male e-waste workers and 51 all-male non-e-waste workers or controls. The concentrations of Cd and Pb were measured in blood and urine using inductively coupled plasma mass spectrometry, while LINE1 methylation levels were assessed by pyrosequencing of bisulfite-converted DNA extracted from whole blood. Single and multiple metals linear regression models were used to determine the associations between metals and LINE1 DNA methylation. RESULTS: Blood lead (BPb) and urine lead (UPb) showed higher median concentrations among the e-waste workers than the controls (76.82 µg/L vs 40.25 µg/L, p ≤ 0.001; and 6.89 µg/L vs 3.43 µg/L, p ≤ 0.001, respectively), whereas blood cadmium (BCd) concentration was lower in the e-waste workers compared to the controls (0.59 µg/L vs 0.81 µg/L, respectively, p = 0.003). There was no significant difference in LINE1 methylation between the e-waste and controls (85.16 ± 1.32% vs 85.17 ± 1.11%, p = 0.950). In our single metal linear regression models, BPb was significantly inversely associated with LINE1 methylation in the control group (ßBPb = - 0.027, 95% CI - 0.045, - 0.010, p = 0.003). In addition, a weak association between BPb and LINE1 was observed in the multiple metals analysis in the e-waste worker group (ßBPb = - 0.005, 95% CI - 0.011, 0.000, p = 0.058). CONCLUSION: Continuous Pb exposure may interfere with LINE1 methylation, leading to epigenetic alterations, thus serving as an early epigenetic marker for future adverse health outcomes.

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries.

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 µg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS: Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Co-exposure of cadmium and lead on bone health in a southwestern Chinese population aged 40-75 years.

Both cadmium (Cd) and lead (Pb) are associated with bone health, but studies exploring the effects of Cd and Pb co-exposure on bone health are rare. This study aimed to assess the interactive effects of Cd and Pb co-exposure on bone health. In total, 799 participants, living in the targeted areas (located in southwestern China) for more than 15 years, aged 40-75 years, and subsisted on homegrown rice and vegetables were investigated. Cd and Pb levels in urine and blood samples, as well as bone mineral density, T- and Z-score were determined. After being adjusted for covariates, the T-score was negatively correlated with blood Pb in men (P < .05); for women and non-smoking women, the T-score was negatively correlated with urinary Pb (P < .05). Moreover, after being adjusted for covariates, the Z-score was negatively correlated with urinary Pb in non-smoking women (P < .05). No positive association of prevalence of osteoporosis with Cd and Pb exposure was found. However, at an additive scale, positive interactions of urinary Cd and Pb on the prevalence of osteoporosis for women and non-smoking women, and the same interactions to blood Cd and Pb for men were found. There was also a positive interaction of urinary Cd and Pb for women at a multiplicative scale. This study suggests Cd and Pb exposure could exert detrimental effects on bone health, with possible underlying interactions. Nevertheless, more studies are needed to explore the interactive effects of heavy metal co-exposure.

Urinary heavy metals, DNA methylation, and subclinical atherosclerosis.

PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.

Effect of exposure to high temperatures in the excretion of cadmium and lead.

OBJECTIVE: This study aims to observe the effect on urine and sweat excretion levels of cadmium (Cd) and lead (Pb) in healthy men in a maximum incremental test until exhaustion and repeated exposure to heat. METHODS: twenty-nine adult men divided into control group (CG; n = 14) and experimental group (EG; n = 15) performing two maximum tests until exhaustion in normothermia (22 °C) and hyperthermia (42 °C). EG experienced 9 sessions of heat exposure at high temperatures (100 °C) (HEHT). After the nine sessions, the initial tests were repeated in both groups. Urine samples were collected before and after each test. After the hyperthermia tests, sweat samples were gathered. RESULTS: Urinary Cd increased after initial tests in GC and in hyperthermia in EG (p < 0.05). Urinary excretion of Pb rose after HEHT (p < 0.05). Pb in sweat was higher in EG than in CG after HEHT (p < 0.05). CONCLUSION: Heat exercise and constant exposure to heat can be a valid method to increase the excretion of toxic metals.

Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace - Part I adjustments to the adult systemic model.

California's Division of Occupational Safety and Health has initiated a process to update its standards for exposure to lead in workplaces. In support of this effort, the state's Office of Environmental Health Hazard Assessment evaluated the age-specific, bio-kinetic model of lead metabolism in humans, originally published by R.W. Leggett in 1993. This model was ultimately chosen for its physiologic realism and practicality in characterizing the relationship between air lead concentrations and blood lead levels in chronically exposed worker and its practicality in making necessary adjustments. Leggett's original model systematically under-predicts bone and blood levels in workers such that several adjustments to the parameters are needed to improve predictions for occupational exposure scenarios. The aim of this work is to incorporate new information about the bio-kinetics of lead in workers and to adjust the Leggett model to improve its predictions.The Leggett model was evaluated by comparing its predictions with information on lead concentrations in bone, blood, and urine from workers and other chronically exposed adults. Key model parameters were identified based upon a review of the relevant exposure assessment and modeling literature. Adjustments to the model parameters were made based on empirical evidence. They included reducing the level of lead in blood (BLL) where the rate of decrease in red blood cell binding begins and ends, lead accumulation rate in cortical bone, the rate of lead elimination in trabecular bone, and rate of lead transferred from diffusible plasma to urine. Regression methods and visual inspection of plotted data were used to assess the effect of adjustments on model predictions. When compared with the original, the adjusted Leggett model more accurately predicted lead concentrations observed in active and retired workers. Also, the adjusted Leggett model required less lead uptake to reach the same BLLs for BLLs less than 25 µg/dL and more time for BLLs to decline than the original Leggett model. These findings are important for defining an adequately protective occupational standard for lead exposure.

Estimates of urinary blood lead clearance and its relationship to glomerular filtration rate based on a large population survey.

Blood lead (Pb) clearance (CbPb) and serum creatinine clearance (CsCr), a metric of glomerular filtration rate (GFR), were estimated in approximately 7,600 subjects from the NHANES (2009-2016). Median CbPb in adults was 0.04 L/day (5th-95th percentile range: 0.01-0.12). Linear regression models explained approximately 68% of variance in CbPb in adults, with >98% of explained variance attributed to CsCr. These results provide an improved quantitative understanding of the possible effects of reverse causality in the interpretation of studies of associations between blood Pb and decrements in GFR.

The association between lead and cadmium co-exposure and renal dysfunction.

Both cadmium (Cd) and lead (Pb) exposure can induce kidney damage. However, the effects of combined exposure to Cd and Pb on renal function at environmental levels have not been fully clarified. In this study we investigated the renal function in a Chinese population co-exposed to Cd and Pb. A total of 331 subjects (215 women and 116 men), living in either a control or a polluted area, were included in this study. Cd and Pb in blood and urine (BCd, BPb, UCd, and UPb), and kidney effect markers including urinary N-acetyl-ß-D-glucosaminidase (UNAG) and estimated glomerular filtration rate (eGFR), were determined, and the association between exposure markers and renal effect biomarkers were analyzed. The exposure levels in the polluted area were significantly higher than in the control area (all p < 0.01). The eGFR of subjects in the polluted area was decreased compared with that in the control area (p < 0.01). The subjects with high BCd/BPb (BCd ≥ 2 µg/L, BPb ≥ 100 µg/L) or high UCd/UPb (UCd ≥ 3 µg/g creatinine, UPb ≥ 10 µg/g creatinine) showed higher UNAG and UALB levels compared with other subgroups (p < 0.01). The probability of having elevated UNAG in subjects with high BCd/BPb was greater than those with low BCd/BPb [odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.4-4.7), low BCd/high BPb (OR =3.1, 95% CI: 1.4-6.6), and high BCd/low BPb (OR = 1.7, 95% CI: 0.9-3.2). The OR of subjects with low UCd and high UPb, high UCd and low UPb, and high UCd/UPb were 2.9 (95% CI: 1.4-5.7), 3.3 (95% CI: 1.5-7.2), and 7.7 (95% CI: 4.0-14.7), respectively, compared with those with low UCd/UPb. The risk of decrease in eGFR was also higher in subjects with high UCd/UPb than for those with low UCd/UPb (OR = 7.2, 95% CI: 0.8-62.2). Our data demonstrate that Cd and Pb exposure, alone or in combination, are associated with renal impairment. In addition, co-exposure to Pb and Cd propagates the renal tubular dysfunction compared with Cd or Pb exposure alone.

Application of Calcium-Binding Motif of E-Cadherin for Electrochemical Detection of Pb(II).

We report, for the first time, the use of a 13-amino-acid peptide sequence derived from the calcium-binding site of E-cadherin in the fabrication of an electrochemical peptide-based (E-PB) Pb(II) sensor. The sensing mechanism is analogous to that of previously developed E-PB sensors. Binding of Pb(II) rigidifies the surface-immobilized and methylene blue (MB)-modified peptide probe, thereby limiting the accessibility of the tethered MB to the electrode surface. This change in probe flexibility results in a reduction in the MB current that is dependent on the target concentration. The sensor behaves as a "signal-off" sensor in alternating current voltammetry and cyclic voltammetry, but it can behave as a "signal-on" sensor in differential pulse voltammetry when a longer pulse width is employed. It is capable of specific detection of Pb(II) and is selective enough to be employed in realistically complex samples such as diluted tap water, saliva, and urine samples. The detection is fast; signal saturation can be achieved in <60 s. The sensor can also be fabricated on gold-plated screen-printed carbon electrodes, electrode substrates that are ideal for cost-effective analysis of Pb(II) in real-world settings.

Biomarkers of exposure and effect in a working population exposed to lead, manganese and arsenic.

Lead (Pb), manganese (Mn) and arsenic (As) are among the major toxicants in mining environments. Miners are commonly and repeatedly exposed to this toxic mixture. Some adverse effects may appear at concentrations below environmental quality guidelines for individual mixture components. Further, Pb, Mn, and As induce common adverse outcomes, such as interferences in the cholinergic system and heme synthesis. It is thus vital to monitor miners through biomarkers (BM), such that subclinical effects may be identified at an early stage. The main objectives of this study were to evaluate the exposure of a mining population to these three metals and determine alterations in cholinergic and heme synthesis parameters. Blood and urine samples of workers (n = 60) were obtained from a Portuguese mining industry and compared with a control population (n = 80). The levels of the metals were determined in biological samples, as well as urinary heme precursor levels, delta aminolevulinic acid (ALA) and porphyrins, and blood acetylcholinesterase (AChE) activity. The miners exhibited significantly higher values of Pb and As in blood and urine compared to control. In the case of Mn near or slightly higher than limit values were found. Our data show that heme precursors may be used simultaneously with metal levels as BMs for multiple metal exposures on an individual basis, resulting in 94.3% and 95.7% accuracy, respectively, in blood and urine, for subjects correctly identified with respect to occupation. This study also revealed that biological monitoring of this working population regarding metal body burden and heme precursor accumulation is advisable.

Integrating multivariate and geostatistical analyses for assessing the socio-environmental vulnerability of children in the vicinity of a contaminated site.

Vulnerability assessments are commonly based on complex indices that may be inappropriate for characterizing risks in small groups of people exposed to environmental hazards. The aim was to present a multivariate and geostatistical approach to explore human health risks at the individual, household and community level. First, biological and socioeconomic characteristics from 179 children were used in a cluster analysis to find groups and identify vulnerability profiles. Then, both the exposure of children to arsenic and lead in soils and their accessibility to community resources were assessed using a geospatial analysis. The results identified three vulnerability profiles among children that were not in agreement with the environmental exposure and deficit of community resources. The proposed approach helps optimize strategies to manage both environmental and social risks based on the vulnerability of the exposed population.

Development of a new method for biomonitoring of multiple metals in occupational exposure.

The assessment of co-exposure to several types of metal contamination poses a hurdle for occupational monitoring. Determination of elements in biological samples is an important way to evaluate occupational exposure. However, optimized methods for the extraction of multiple metals from biological samples have not been reported in recent studies. Therefore, solid-phase extraction (SPE) based on the functionalized nano-zeolite Y was suggested for the biomonitoring of metal co-exposure. SPE was conducted with ammonium pyrrolidine dithiocarbamate (APDC) surrounded by Triton X-100 micelles, which were loaded into the pores of nano-zeolite Y. In this study, SPE was optimized for pre-concentration of trace amounts of chromium (Cr), cadmium (Cd), and lead (Pb) in urine samples with respect to the pH, APDC concentration, elution condition, amount of functionalized nano-zeolite Y, and sample volume. This method has been successfully optimized for the extraction of the mentioned multiple metals with >97% efficiency and an acceptable reproducibility with a coefficient variation of <10%. This method could be used in the extraction of multiple metals in environmental and occupational exposure conditions. In this study, urine samples of welding workers were evaluated following this optimized method.

The decline in kidney function with chromium exposure is exacerbated with co-exposure to lead and cadmium.

Environmental factors contribute significantly to the pathogenesis of chronic kidney disease. However, these factors, and particularly the toxic effects of heavy metals, have not been completely evaluated. Chromium is a widespread industrial contaminant that has been linked to nephrotoxicity in animal and occupational population studies. Nevertheless, its role in population renal health and its potential interactions with other nephrotoxic metals, such as lead and cadmium, remain unknown. We assessed the association between exposure to chromium, lead, and cadmium with renal function using estimated glomerular filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19-84 years from the National Nutrition and Health Survey in Taiwan (2005-2008). Doubling of urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m2 (95% confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after adjusting for age, sex, body mass index, hypertension, diabetes, cigarette smoking, sodium intake, education, urinary volume, and other metals. For those in the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73 m2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m2 (-17.01, -5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a significant and independent association between chromium exposure and decreased renal function. Furthermore, co-exposure to chromium with lead and cadmium is potentially associated with additional decline in the glomerular filtration rate in Taiwanese adults.

Facile Chip-Based Array Monolithic Microextraction System Online Coupled with ICPMS for Fast Analysis of Trace Heavy Metals in Biological Samples.

Trace heavy metals have great impact on biological system; therefore, it is essential to develop suitable analytical methods for the determination of trace heavy metals in biological samples to elucidate their biochemical and physiological functions in organisms. Herein, we presented a chip-based array monolithic microextraction system and combined it with inductively coupled plasma mass spectrometry (ICPMS) for online analysis of trace Hg, Pb, and Bi in real-world biological samples. Six ethylenediamine modified poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (poly(GMA-co-EDMA-NH2)) capillary monolithic columns were embedded parallelly in microchannels of a microfluidic chip for array monolithic microextraction. Various parameters affecting the chip-based array monolithic microextraction of target metals were investigated. The sample throughput of the proposed method was 16 h-1, with the limits of detection for Hg, Pb, and Bi of 23, 12, and 13 ng L-1, respectively. The developed method was validated by the determination of trace Hg, Pb, and Bi in HepG2 cells and human urine samples, and the recoveries for the spiked samples were in the range of 90.4-102%. This chip-based array monolithic microextraction system is easy to prepare, and the proposed online analytical system provides a new platform for trace elements analysis in biological samples with the merits of high sample throughput, high sensitivity, and low sample/reagents consumption.

Gestational exposure to endocrine disrupting chemicals in relation to infant birth weight: a Bayesian analysis of the HOME Study.

BACKGROUND: Pregnant women are exposed to a mixture of endocrine disrupting chemicals (EDCs). Gestational EDC exposures may be associated with changes in fetal growth that elevates the risk for poor health later in life, but few studies have examined the health effects of simultaneous exposure to multiple chemicals. This study aimed to examine the association of gestational exposure to five chemical classes of potential EDCs: phthalates and bisphenol A, perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) with infant birth weight. METHODS: Using data from the Health Outcomes and Measures of Environment (HOME) Study, we examined 272 pregnant women enrolled between 2003-2006. EDC concentrations were quantified in blood and urine samples collected at 16 and 26 weeks gestation. We used Bayesian Hierarchical Linear Models (BHLM) to examine the associations between newborn birth weight and 53 EDCs, 2 organochlorine pesticides (OPPs) and 2 heavy metals. RESULTS: For a 10-fold increase in chemical concentration, the mean differences in birth weights (95% credible intervals (CI)) were 1 g (-20, 23) for phthalates, -11 g (-52, 34) for PFAS, 0.2 g (-9, 10) for PCBs, -4 g (-30, 22) for PBDEs, and 7 g (-25, 40) for OCPs. CONCLUSION: Gestational exposure to phthalates, PFAS, PCBs, PBDEs, OCPs or OPPs had null or small associations with birth weight. Gestational OPP, Pb, and PFAS exposures were most strongly associated with lower birth weight.