Multiple Metal Exposure Research Articles

Associations between multiple serum metal exposures and low birth weight infants in Chinese pregnant women: A nested case-control study

To investigate the associations between prenatal exposure to single metal and multiple metals and the risk of low birth weight (LBW), we conducted a nested case-control study of 246 LBW and 406 NBW mother-infant pairs based on a prospective birth cohort study. 22 serum metals were detected by inductively coupled plasma quadruple mass spectrometry (ICP-MS). Categorical analyses showed serum Co and Ti were associated with LBW (Co: 3rd vs 4th. quartile: OR = 1.83, 95%CI: 1.14–2.92, Ptrend = 0.043; Ti: 2nd vs. 4th quartile: OR = 0.51, 95% CI: 0.32–0.81, P trend = 0.051), especially gestational age >13 weeks (Co: 3rd vs. 4th quartile: OR = 1.94, 95% CI: 1.13 - 3.32, Ptrend = 0.043; Ti: 2nd vs. 4th quartile: OR = 0.50, 95% CI: 0.30 - 0.84, P trend= 0.073). Cubic spline analyses showed serum Co and serum Ti had non-linearity associations with LBW (Co: P for overall = 0.048, P-nonlinearity = 0.014; Ti: P for overall = 0.015, P- nonlinearity = 0.008). In multi-metal compound exposure model, 15 metals selected by elastic net model were significantly associated with the increased risk of LBW and OR (95%CI) was 5.14 (2.81–9.40). Our study suggested that lower level serum Co was positively associated with LBW and lower level serum Ti was negatively associated with LBW, especially gestational age >13 weeks, and both of them had non-linearity dose-relationships with LBW. And multi-metal compound model was significantly associated with LBW compared with single metal model.

Multiple metals exposure and chromosome damage: Exploring the mediation effects of microRNAs and their potentials in lung carcinogenesis

ObjectiveThis study aimed to investigate the associations of multiple metals with chromosome damage, and further explore the mediation roles of microRNAs (miRNAs) and their potentials in lung cancer. MethodsWe determined the urinary levels of 23 metals, lymphocytic micronucleus (MN) frequency, and ten candidate miRNAs in plasma among 365 healthy workers. Poisson and linear regression models were conducted to analyze the associations of urinary metals with MN frequency and miRNAs, respectively. The mediation effects of miRNAs on the metal-MN frequency associations were assessed by causal mediation analysis. Additionally, the levels of effective metal and miRNAs were measured in 43 pair-wised tumor and normal lung tissues. ResultsThe urinary level of titanium was inversely associated with MN frequency after Bonferroni correction [frequency ratio (FR) and 95% confidence interval (95%CI) = 0.88 (0.82, 0.94), p = 5.0 × 10−4]. A doubling in urinary titanium was associated with 14.72%–38.17% decrease in plasma miRNAs. After multiple comparison, miR-24-3p and miR-28-5p significantly mediated 24.8% (7.7%, 70.0%) and 20.4% (5.7%, 52.0%) of the association between titanium and MN frequency (pmediation = 0.002 and 0.004, respectively). Besides, a doubling in titanium was associated with a separate 53.4% and 47.2% decreased miR-24-3p and miR-28-5p expression in normal lung tissues. Lower titanium but higher levels of miR-24-3p and miR-28-5p were shown in tumor than normal tissues of lung squamous cell carcinoma patients (all p < 0.05). ConclusionsOur study proposed the negative associations of titanium with chromosome damage and lung cancer, and highlighted the mediating roles of miR-24-3p and miR-28-5p. Further investigations are warranted to validate these associations and uncover the underlying mechanisms.

Multiple metal exposures and metabolic syndrome: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2011–2014

BackgroundEpidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress. ObjectivesWe sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions. MethodsUsing data from the 2011–2014 National Health and Nutrition Examination Survey (n = 1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ≥ 3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity. ResultsAfter adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18–1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78–1.16) for the methylmercury-manganese pattern, 0.73 (0.57–0.94) for the cadmium-lead pattern, 0.91 (0.76–1.10) for the copper pattern, and 1.36 (1.13–1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity. ConclusionsThese cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.

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

ABSTRACT 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.

Field and laboratory evaluation of DGT for predicting metal bioaccumulation and toxicity in the freshwater bivalve Hyridella australis exposed to contaminated sediments

The diffusive gradients in thin films (DGT) technique has shown to be a useful tool for predicting metal bioavailability and toxicity in sediments, however, links between DGT measurements and biological responses have often relied on laboratory-based exposures and further field evaluations are required. In this study, DGT probes were deployed in metal-contaminated (Cd, Pb, Zn) sediments to evaluate relationships between bioaccumulation by the freshwater bivalve Hyridella australis and DGT-metal fluxes under both laboratory and field conditions. The DGT-metal flux measured across the sediment/water interface (±1 cm) was useful for predicting significant cadmium and zinc bioaccumulation, irrespective of the type of sediment and exposure. A greater DGT-Zn flux measured in the field was consistent with significantly higher zinc bioaccumulation, highlighting the importance of performing metal bioavailability assessments in situ. In addition, DGT fluxes were useful for predicting the potential risk of sub-lethal toxicity (i.e., lipid peroxidation and lysosomal membrane damage). Due to its ability to account for multiple metal exposures, DGT better predicted bioaccumulation and toxicity than particulate metal concentrations in sediments. These results provide further evidence supporting the applicability of the DGT technique as a monitoring tool for sediment quality assessment.

Analysis of spatial distribution of trace metals, PCB, and PAH and their potential impact on human health in Virginian Counties and independent cities, USA.

Increasing anthropogenic alteration has resulted in increased exposure to both point and nonpoint source pollution. These exposures are increasingly studied for their role in human diseases, including diseases with known genetic or lifestyle risk factors. This study analyzed associations between a variety of human diseases and trace metals, PCBs, and PAHs in soil, groundwater, sediment, and fish. Contaminant spatial data at the county level from Virginia were used in ArcGIS to identify these associations among socially vulnerable populations. The neurologic and psychiatric disorders and cognitive markers were associated with numerous metals in groundwater/soil and/or aquatic system contaminants. Cancer death rates, fetal deaths, and infant deaths were also related to multiple environmental exposures from both categories of exposure. In contrast, many of the chronic diseases which are primarily attributed to lifestyle showed little association with these exposures with the exception of COPD which did appear to be associated with multiple metal exposures. Asthma showed similar associations compared to COPD. Our data suggest that within the context of socially vulnerable populations, where disease burden is often highest, exposures to metals, PAHs, and PCBs may play a role in the development or exacerbation of several highly prevalent categories of disease. These environmental exposures likely act through a variety of pathways all generally leading to increased oxidative stress, inflammation, or interference with biological systems and a subsequent role in disease development.

Assessment of occupational exposures to multiple metals with urinary porphyrin profiles.

Chronic occupational exposures to low levels of metal mixtures necessitates biomonitoring of exposed workers. However, a single biomarker (BM) is rarely sufficient to ascertain the exposure of an individual to a complex mixture, with multiparameter analysis of the same sample considered recently as a preferred approach. Porphyrins are formed as intermediates of heme biosynthesis and different metals can exert their effects at different points of this metabolic pathway, leading to changed urinary porphyrins excretion profiles. The aim of this work was to develop a model that could serve to identify, on an individual basis, multiple metal exposure resulting from mining work, by using urinary porphyrin profiles. Urine samples of workers were obtained from a Portuguese mining company and a non-occupationally exposed group was used as control. The levels of uro-, hepta-, hexa-, penta-, copro- and protoporphyrins were determined by HPLC. It was observed that only heptaporphyrin levels in miners were significantly (p<0.05) different from controls. However, when the concentrations of all porphyrins were combined by binary logistic regression, their ability to discriminate between miners and controls was higher than each one of the porphyrins alone, as indicated by a greater curve' area under a ROC curve. Moreover, when the combined porphyrins were used to calculate the probability of each subject fit in the occupationally exposed group, 83% of 47 individuals were correctly identified with respect to their type of exposure. These results suggest that the integration of the urinary porphyrin profile is a promising tool for the detection of subjects exhibiting biochemical modifications due to occupational exposure to metals in mines.

Multiple-metal exposure, diet, and oxidative stress in Uruguayan school children

Oxidative stress (OS) is an important consequence of exposure to toxic metals but it is unclear to what extent low-level metal exposures contribute to OS in children. We examined the cross-sectional association between urinary concentrations of arsenic (As), cadmium (Cd), and lead (Pb) and urinary markers of OS: F2–8α isoprostane and 8-hydroxy-2-deoxy-guanosine (8-OHdG). We also tested effect modification by dietary intakes. Of the 211 children aged 6–8 years living in Montevideo who were eligible for the study because they had at least one OS marker measured via ELISA, 143 were included in a complete-case analysis. Urinary metals were measured with inductively coupled plasma mass spectrometry (ICP-MS: Pb, Cd) and high-performance liquid chromatography online with hydride generation ICP-MS (As-metabolites); concentrations were log2-transformed. All urinary markers were adjusted for specific gravity of urine. Two 24-h dietary recalls were conducted to estimate children's dietary intakes, including total fruit and vegetable consumption and vitamin C, zinc and fiber intake. Ordinary least square (OLS) and weighted quantile sum (WQS) regressions were used to estimate the association between metals and each OS marker as outcome. Metal exposure was generally low: median urinary As, Cd, Pb 9.6 μg/L, 0.06 μg/L and 1.9 μg/L, respectively. Median 8-isoprostane concentration was 1.1 and 8-OHdG 39.6 ng/mL. Log2-transformed urinary As concentrations were positively associated with 8-OHdG concentrations (10.90 [3.82, 17.97]) in covariate-adjusted OLS models which also took account of exposure to Cd and Pb. In WQS, a mixture index was also associated with higher 8-OHdG (8.71 [1.12, 16.3] for each 25% increase in index value), mostly driven by As exposure. There was little evidence of effect modification by dietary antioxidants. In sum, even at low-level, As exposure is associated with detectable oxidative damage to the DNA.

Multiple metal exposures and their correlation with monoamine neurotransmitter metabolism in Chinese electroplating workers

Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples. Multivariate linear regression model was used to assess the dose-response relationships of urinary metals and neurotransmitter pathway metabolites. Significant dose-dependent trends of urinary vanadium quartiles with all metabolites were observed, and the trends demonstrated significance after multiple testing correction. It also showed that urinary chromium levels were significantly associated with decreased serotonin level and cadmium was positively associated with norepinephrine and epinephrine. In addition, arsenic was positively associated with tryptophan, serotonin, dopamine and norepinephrine. Iron was positively associated with increased homovanillic acid (HVA) and epinephrine while nickel was negatively associated with increased epinephrine levels. Zinc was positively related to tryptophan, kynurenin (KYN), 5-hydroxyindole acetic acid (5-HIAA), dopamine, HVA and norepinephrine. There was no significant association between urinary copper with any other metabolites after adjusting of multiple metal models. Metal exposure may be associated with neurotransmitter metabolism disturbances. The present work is expected to provide some support in the prevention and management of metal-associated neurological diseases.

Multiple heavy metal exposure and effects on intellectual function in Ecuadorian children

Multiple heavy metal exposure and effects on intellectual function in Ecuadorian children

Decreased vaccine antibody titers following exposure to multiple metals and metalloids in e-waste-exposed preschool children

We explored acquired immunity resulting from vaccination in 3 to 7-year-old children, chronically exposed to multiple heavy metals and metalloids, in an e-waste recycling area (Guiyu, China). Child blood levels of ten heavy metals and metalloids, including lead (Pb), arsenic (As), mercury (Hg), chromium (Cr), cadmium (Cd), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn) and selenium (Se), and seven vaccine antibodies (diphtheria, pertussis, tetanus, hepatitis B, Japanese encephalitis, polio, measles) were measured. The exposed group had higher levels of blood Pb, Mn, Cu, Zn and Cr compared to the reference group (P < 0.05). Levels of all vaccine antibodies in the exposed group were significantly lower than in the reference group (P < 0.01). All vaccine antibodies negatively correlated with blood concentrations of Cu, Zn and Pb, based on spearman rank correlation analysis. Multiple logistic regression and univariate analyses identified the location of residence (Guiyu), high blood Pb (>10 μg/dL) and high blood Cu and Zn (upper median value of each group) to be inversely associated with seven antibody titers. Antibody titers increased with age, BMI, high blood Mn (>15 μg/L), and high blood Cd and Ni (upper median value of each group). Results suggest multiple heavy metal and metalloid exposure, especially to Pb, Zn and Cu, may be a risk factor inhibiting the development of child immunity, resulting in decreased child antibody levels against vaccines.

Multiple metals exposure, elevated blood glucose and dysglycemia among Chinese occupational workers

AimsExposure to metals may adversely affect cardiometabolic health. The aim of this study is to directly evaluate the roles of multiple metals exposure in glucose homeostasis, the dysfunction of which has been linked to diabetes and cardiovascular diseases (CVDs). MethodsWe performed a cross-sectional analysis of baseline data from 464 metal-exposed workers who participated in a large prospective occupational study in China (Jinchang Cohort). The logistic regression model was used to evaluate the association between urinary metal levels and high fasting plasma glucose (high-FPG) (≥ 75th percentile) and dysglycemia. ResultsIncreasing levels of urinary nickel were prospectively associated with high-FPG: multivariable odds ratios (ORs) were 1.00 for the 1st quartile (lowest), 1.20 (95% confidence interval [CI]: 0.60–2.43) for the 2nd quartile, 1.64 (0.78–3.49) for the 3rd quartile and 3.17 (1.38–7.30) for the 4th quartile (highest) (P-trend=0.004). The positive associations were also observed between urinary zinc and high-FPG (4th vs. 1st quartile=2.71, 95%CI: 1.26–5.84, P-trend=0.01). Inverse associations between urinary cobalt and risk of high-FPG and dysglycemia were observed (P-trend <0.05). For dysglycemia, the positive trends of increasing levels of urinary nickel and zinc still remained, although urinary nickel was no longer statistically significant. A significant association between urinary arsenic and dysglycemia was also found. However, no associations were observed between urinary copper, cadmium, and risk of high-FPG or dysglycemia. ConclusionMultiple urinary metals, particularly arsenic, nickel, zinc, and cobalt, were associated with elevated blood glucose among Chinese occupational workers, supporting the notion that metal exposure plays a critical role in the development of diabetes.

Application of biotic ligand and toxicokinetic–toxicodynamic modeling to predict the accumulation and toxicity of metal mixtures to zebrafish larvae

Predicting the accumulation and toxicity of mixtures of metals to aquatic organisms is a key challenge in ecotoxicological studies. In this study, the accumulation and toxicity of mixed essential (Cu) and nonessential (Cd and Pb) metals in zebrafish larvae exposed to a binary mixture of these elements at environmentally relevant concentrations were predicted using a refined toxicokinetic (TK)–toxicodynamic (TD) model aided with biotic ligand model (BLM) and toxic equivalent factor (TEF) approach. Competitive inhibition and non-competitive interaction/inhibition were observed in bio-uptake. Both Pb and Cd behaved as competitive inhibitors of Cu uptake at high Cu concentrations (>0.1 μM). By contrast, Cu uptake was independent of Cd or Pb when the Cu concentrations were below 10−7 M. Furthermore, low concentrations of Cu had an adiaphorous effect on Cd or Pb uptake. Cd uptake was inhibited by Pb, and the Pb uptake rates consistently decreased in the presence of Cd. The accumulation processes of Cd–Pb, Cu–Cd, and Cu–Pb were accurately predicted by the BLM-aided TK models. The traditional TD model could successfully predict the toxicity of Cd–Pb mixtures, but not those of Cu–Cd or Cu–Pb mixtures. The revised TD model, which considered the possible different killing rates (Kk) above or below the threshold, offered better prediction for the toxicity of Cu–Cd or Cu–Pb mixtures. The overall findings may be of key significance in understanding and predicting metal uptake, accumulation, and toxicity in binary or multiple metal exposure scenarios.

Associations of Low Environmental Exposure to Multiple Metals with Renal Tubular Impairment in Korean Adults.

Recently several studies reported that the renal toxicity of lead (Pb) and cadmium (Cd) may exist in even a low level exposure. In terms of the deterioration of tubular function, it affects the loss of divalent metals and leads to other complications, so renal tubular effect of heavy metals should be well managed. Considering the exposure to heavy metals in reality, it is hard to find the case that human is exposed to only one heavy metal. We designed a cross-sectional study using Korean Research Project on the Integrated Exposure Assessment (KRIEFS) data to investigate the renal effects of multiple metal exposure in general population. We used blood Pb and urinary Cd as exposure measures, and urinary N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin (β2-MG) as renal tubular impairment outcome. We conducted linear regression to identify the association between each heavy metal and urinary NAG and β2-MG. And then, we conducted linear regression including the interaction term. Of 1953 adults in KRIEFS (2010~2011), the geometric mean of blood Pb and urinary Cd concentration was 2.21 μg/dL (geometric SD = 1.49 μg/dL) and 1.08 μg/g cr (geometric SD = 1.98 μg/g cr), respectively. In urinary Cd, the strength of the association was also high after adjusting (urinary NAG: β = 0.44, p < 0.001; urinary β2-MG: β = 0.13, p = 0.002). Finally, we identified the positive interactions for the two renal biomarkers. The interaction effect of the two heavy metals of β2-MG was greater than that of NAG. It is very important in public health perspective if the low level exposure to multiple heavy metals has an interaction effect on kidney. More epidemiological studies for the interaction and toxicological studies on the mechanism are needed.

Metal uptake of Nerium oleander from aerial and underground organs and its use as a biomonitoring tool for airborne metallic pollution in cities.

The analysis of the airborne particulate matter-PM-incorporated to plant leaves may be informative of the air pollution in the surroundings, allowing their use as biomonitoring tools. Regarding metals, their accumulation in leaves can be the result of both atmospheric incorporation of metallic PM on aboveground plant organs and root uptake of soluble metals. In this study, the use of Nerium oleander leaves as a biomonitoring tool for metallic airborne pollution has been assessed. The metal uptake in N. oleander was assessed as follows: (a) for radicular uptake by irrigation with airborne metals as Pb, Cd, Cr, Ni, As, Ce and Zn (alone and in mixture) and (b) for direct leave exposure to urban PM. Plants showed a high resistance against the toxicity of metals under both single and multiple metal exposures. Except for Zn, the low values of translocation and bioaccumulation factors confirmed the excluder behaviour of N. oleander with respect to the metals provided by the irrigation. For metal uptake from airborne pollution, young plants grown under controlled conditions were deployed during 42days in locations of the city of Zaragoza (700,000h, NE Spain), differing in their level of traffic density. Samples of PM2.5 particles and the leaves of N. oleander were simultaneously collected weekly. High correlations in Pb concentrations were found between leaves and PM2.5; in a lesser extent, correlations were also found for Fe, Zn and Ti. Scanning electron microscopy showed the capture of airborne pollution particles in the large and abundant substomatal chambers of N. oleander leaves. Altogether, results indicate that N. Oleander, as a metal resistant plant by metal exclusion, is a suitable candidate as a biomonitoring tool for airborne metal pollution in urban areas.

Assessment of toxic metals in groundwater and saliva in an arsenic affected area of West Bengal, India: A pilot scale study

Communities in many parts of the world are unintentionally exposed to arsenic (As) and other toxic metals through ingestion of local drinking water and foods. The concentrations of individual toxic metals often exceed their guidelines in drinking water but the health risks associated with such multiple-metal exposures have yet to receive much attention. This study examines the co-occurrence of toxic metals in groundwater samples collected from As-rich areas of Nadia district, West Bengal, India. Arsenic in groundwater (range: 12–1064µgL−1; mean ± S.D: 329±294µgL−1) was the most important contaminant with concentrations well above the WHO guideline of 10µgL−1. Another important toxic metal in the study area was manganese (Mn) with average concentration of 202±153µgL−1, range of 18–604µgL−1. The average concentrations (µgL−1) of other elements in groundwater were: Cr (5.6±5.9), Mo (3.5±2.1), Ni (8.3±8.7), Pb (2.9±1.3), Ba (119±43), Zn (56±40), Se (0.60±0.33), U (0.50±0.74). Saliva collected from the male participants of the area had mean concentrations of 6.3±7.0µg As L−1 (0.70–29µgL−1), 5.4±5.5µg Mn L−1 (0.69–22µgL−1), 2.6±3.1µg Ni L−1 (0.15–13µgL−1), 0.78±1.0µg Cr L−1 (<DL–5.9µgL−1), 0.94±0.90µg Pb L−1 (<DL–4.2µgL−1), 0.56±0.37µg Se L−1 (0.11–1.5µgL−1) and 194±54µg Zn L−1 (112–369µgL−1). The high concentrations of salivary As and Mn are believed to be indicative of intake from the groundwater. The clustering of salivary As and Mn in principal component analysis further indicated influence of the common exposure source. Zinc and selenium comprised a separate component presumably reflecting the local deficiencies in intakes of these essential elements from drinking water and foodstuff. Thus the study reveals that the concentration of other metals beside As must be monitored in drinking water before implementation of any policies to provide safe water to the affected communities.

Metallic Burden of Deciduous Teeth and Childhood Behavioral Deficits.

Attention Deficit/Hyperactivity Disorder (ADHD) affects 5%–8% of children in the U.S. (10% of males and 4% of females). The contributions of multiple metal exposures to the childhood behavioral deficits are unclear, although particular metals have been implicated through their neurotoxicity. The objective of this study was to test the hypothesis that the body burden of Mn is positively correlated with ADHD symptoms. We also investigated the putative roles of Ca, Fe, Pb, and Hg. We collected shed molars from 266 children (138 boys and 128 girls) who lost a tooth between 11 and 13 years of age. The molars were analyzed for metals using ICP-OES. The third grade teacher of each child completed the Teacher’s Disruptive Behavior Disorders Rating Scale (DBD) to produce a score for “Total Disruptive Behavior” and subscale scores for “Attention Deficit Hyperactivity Disorder”, Hyperactivity/Impulsivity, Inattention, and Oppositional/Defiant. The mean Mn, Fe, Pb and Ca concentrations found in teeth was 3.1 ± 2.9 µg/g, 11.4 ± 12.1 µg/g, 0.5 ± 0.7 µg/g, and 3.0 × 105 ± 0.8 × 105 µg/g, respectively. Hg was not detected. No significant association was found between Mn and behavioral deficits. Ca was significantly negatively associated, and Pb showed a significant positive association with Hyperactivity/Impulsivity, Inattention, and Oppositional/Defiant Disorders. These findings call into question the putative independent association of manganese exposure and behavioral deficits in children, when the balance of other metallic burden, particularly Ca and Pb burdens play significant roles.

Modeling and interpreting biological effects of mixtures in the environment: introduction to the metal mixture modeling evaluation project.

The fate and biological effects of chemical mixtures in the environment are receiving increased attention from the scientific and regulatory communities. Understanding the behavior and toxicity of metal mixtures poses unique challenges for incorporating metal-specific concepts and approaches, such as bioavailability and metal speciation, in multiple-metal exposures. To avoid the use of oversimplified approaches to assess the toxicity of metal mixtures, a collaborative 2-yr research project and multistakeholder group workshop were conducted to examine and evaluate available higher-tiered chemical speciation-based metal mixtures modeling approaches. The Metal Mixture Modeling Evaluation project and workshop achieved 3 important objectives related to modeling and interpretation of biological effects of metal mixtures: 1) bioavailability models calibrated for single-metal exposures can be integrated to assess mixture scenarios; 2) the available modeling approaches perform consistently well for various metal combinations, organisms, and endpoints; and 3) several technical advancements have been identified that should be incorporated into speciation models and environmental risk assessments for metals.

Chronic Metal Exposure, Air Pollution and Cancer in Haifa, Israel

Air pollution is a worldwide problem to millions of people exposed to concentrations of air pollutants above safety standards, including fine particulate matter (PM2.5). In Haifa, Israel, the apparent link between pollution and cancer development is a topic of concern. The study focused on evaluating the metal exposure of children and adults residing in the Haifa area. A high toxic burden to combustion metals such as nickel and potential carcinogens such as mercury was determined. Samples of hair were collected from people living in and around Haifa between 2007 and 2015. Selected patients were separated into three groups, adult males and females, and children with a median age of 6.6 years. Multiple metal exposure was determined in all groups, with the greatest burden found in children.

Patterns of exposure to multiple metals and associations with neurodevelopment of preschool children from Montevideo, Uruguay.

While it is known that toxic metals contribute individually to child cognitive and behavioral deficits, we still know little about the effects of exposure to multiple metals, particularly when exposures are low. We studied the association between children's blood lead and hair arsenic, cadmium, and manganese and their performance on the Bayley Scales of Infant Development III. Ninety-two preschool children (age 13–42 months) from Montevideo, Uruguay, provided a hair sample and 78 had a blood lead level (BLL) measurement. Using latent class analysis (LCA), we identified four groups of exposure based on metal concentrations: (1) low metals, (2) low-to-moderate metals, (3) high lead and cadmium, and (4) high metals. Using the four-group exposure variable as the main predictor, and fitting raw scores on the cognitive, receptive vocabulary, and expressive vocabulary scales as dependent variables, both complete-case and multiple imputation (MI) analyses were conducted. We found no association between multiple-metal exposures and neurodevelopment in covariate-adjusted models. This study demonstrates the use of LCA together with MI to determine patterns of exposure to multiple toxic metals and relate these to child neurodevelopment. However, because the overall study population was small, other studies with larger sample sizes are needed to investigate these associations.