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The placenta is a mixture of cell types, which may regulate maternal-fetal transfer of exogenous chemicals or become altered in response to exposures. We leveraged placental DNA methylation to characterize major constituent cell types and applied compositional data analysis to test associations with non-essential metal(loid)s measured in paired umbilical cord tissue (N = 158). Higher proportions of syncytiotrophoblasts were associated with lower arsenic, whereas higher proportions of Hofbauer cells were associated with higher cadmium concentrations in umbilical cords. These findings suggest that placental cellular composition influences amounts of metal(loid)s transferred to the fetus or that prenatal exposures alter the placental cellular makeup. • Proportions of cell types in the placenta vary substantially. • DNA methylation revealed trophoblasts were rare, syncytiotrophoblasts most abundant. • More syncytiotrophoblasts linked to lower amounts of arsenic in umbilical cords. • More Hofbauer cells linked to higher amounts of cadmium in umbilical cords. [ABSTRACT FROM AUTHOR]

The principal goal of this study was to investigate the uptake and distribution of lead (Pb) in the horns of Pb-dosed goats, and to explore possible links to their historical Pb dosing records. Horn is a keratinized material that grows in discrete increments with the potential to preserve the historical record of past environmental exposures. While previous studies have leveraged this potential to examine environmental and biological phenomena in horns, Pb uptake has never been explored. Horns were collected post-mortem from three goats that had been previously used to produce blood lead reference materials for the New York State proficiency testing program. The animals were periodically dosed with lead acetate, administered orally in a capsule, over a 5 to 8-year period. Horn cross sections were taken from each animal and analyzed using synchrotron radiation-induced micro X-ray fluorescence spectrometry (SR-μXRF) at the Cornell High Energy Synchrotron Source (CHESS). Elemental distribution maps were obtained by SR-μXRF for Pb, Ca, S, Se, and three other elements (Br, Zn and Cu), with values reported quantitatively as a mass fraction (μg/g for trace elements and mg/g for Ca and S). Accumulations of Pb were clearly visible as a series of narrow "rings" in each of the horn samples analyzed. The elements Ca, S, Br, Zn, and Cu were also detected as discrete rings within each cross-section, with Br strongly correlated with S in the samples examined. A marginal increase in Se may coincide with Pb accumulation in horn cross-sections. Annual mineralization estimates based on the relative distribution of Ca and S were used to establish a tentative timeline for horn growth, with each timeline linked to the pattern of Pb accumulation in the corresponding horn cross-section sample. Following ingestion, absorbed Pb is eventually deposited into caprine horns, resulting in discrete accumulations or "rings." Elemental mapping by SR-μXRF clearly show Ca-rich layers that vary with annual periodicity, consistent with previous reports of horn mineralization. Localized enrichment of Cu, Zn, Br and S appear to coincide with the keratinized regions related to the annual growth ring pattern in horns. Spatial analysis of horns for Pb accumulation may be useful as a qualitative marker of time-resolved exposures that may reflect specific periods of acute Pb absorption. [ABSTRACT FROM AUTHOR]

Patients receiving long-term parenteral nutrition (PN) are exposed to potentially toxic elements, which may accumulate in bone. Bone samples collected from seven PN patients (average = 14 years) and eighteen hip/knee samples were analyzed for Al as part of a previous investigation. Yttrium was serendipitously detected in the PN bone samples, leading to the present investigation of rare earth elements (REEs). A method for quantitating fifteen REEs in digested bone was developed based on tandem ICP-MS (ICP-MS/MS) to resolve spectral interferences. The method was validated against nine biological reference materials (RMs) for which assigned values were available for most REEs. Values found in two NIST bone SRMs (1400 Bone Ash and 1486 Bone Meal) compared favorably to those reported elsewhere. Method detection limits ranged from 0.9 ng g −1 (Tm) to 5.8 ng g −1 (Y). Median REE values in the PN patient group were at least fifteen times higher than the “control” group, and exceeded all previously reported data for eleven REEs in human bones. REE content in PN bones normalized to the Earth’s upper crust revealed anomalies for Gd in two patients, likely from exposure to Gd-containing contrast agents used in MRI studies. A retrospective review of the medical record for one patient revealed an almost certain case of nephrogenic systemic fibrosis, associated with Gd exposure. Analysis of two current PN formulations showed traces of REEs with relative abundances similar to those found in the PN bones, providing convincing evidence that PN solutions were the primary source of REEs in this population. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether lead-containing shields have lead dust on the external surface.Methods: Institutional review board approval was obtained for this descriptive study of a convenience sample of 172 shields. Each shield was tested for external lead dust via a qualitative rapid on-site test and a laboratory-based quantitative dust wipe analysis, flame atomic absorption spectrometry (FAAS). The χ2 test was used to test the association with age, type of shield, lead sheet thickness, storage method, and visual and radiographic appearance.Results: Sixty-three percent (95% confidence interval [CI]: 56%-70%) of the shields had detectable surface lead by FAAS and 50% (95% CI: 43%-57%) by the qualitative method. Lead dust by FAAS ranged from undetectable to 998 μg/ft2. The quantitative detection of lead was significantly associated with the following: (1) visual appearance of the shield (1 = best, 3 = worst): 88% of shields that scored 3 had detectable dust lead; (2) type of shield: a greater proportion of the pediatric patient, full-body, and thyroid shields were positive than vests and skirts; (3) use of a hanger for storage: 27% of shields on a hanger were positive versus 67% not on hangers. Radiographic determination of shield intactness, thickness of interior lead sheets, and age of shield were unrelated to presence of surface dust lead.Conclusions: Sixty-three percent of shields had detectable surface lead that was associated with visual appearance, type of shield, and storage method. Lead-containing shields are a newly identified, potentially widespread source of lead exposure in the health industry. [ABSTRACT FROM AUTHOR]

Abstract: Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may interfere with in vitro fertilization (IVF). The aim of this study is to explore biologically plausible hypotheses concerning associations between metals and embryo quality indicators during IVF. For 24 female patients, a multivariable ordinal logistic regression model suggests a 75% reduction in the odds for higher embryo cell cleavage per μg/dL increase in blood Pb (adjusted odds ratio (aOR) 0.25, 95% confidence interval (CI) 0.07–0.86). For 15 male partners, each μg/L increase in blood Hg (aOR 0.60, 95% CI 0.45–0.79) and μg/dL increase in blood Pb (aOR 0.58, 95% CI 0.37–0.91) is associated with a decrease in the analogous odds. Embryo fragmentation is reduced by higher blood Hg (aOR 0.85, 95% CI 0.72–1.00), but increased by higher blood Pb (aOR 1.47, 95% CI 1.11–1.94) in men. The magnitude of these suggested effects warrants confirmation in a larger study. [Copyright &y& Elsevier]

Abstract: Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each μg/dL increase in blood Pb concentration (relative risk (RR)=0.25, 95% confidence interval (CI) 0.03–2.50, P =0.240). For 15 male IVF partners, each μg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR=0.19, 95% CI 0.03–1.35, P =0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses. [Copyright &y& Elsevier]

Abstract: Excessive exposure to aluminum (Al) can produce serious health consequences in people with impaired renal function, especially those undergoing hemodialysis. Al can accumulate in the brain and in bone, causing dialysis-related encephalopathy and renal osteodystrophy. Thus, dialysis patients are routinely monitored for Al overload, through measurement of their serum Al. Electrothermal atomic absorption spectrometry (ETAAS) is widely used for serum Al determination. Here, we assess the analytical performances of three ETAAS instruments, equipped with different background correction systems and heating arrangements, for the determination of serum Al. Specifically, we compare (1) a Perkin Elmer (PE) Model 3110 AAS, equipped with a longitudinally (end) heated graphite atomizer (HGA) and continuum-source (deuterium) background correction, with (2) a PE Model 4100ZL AAS equipped with a transversely heated graphite atomizer (THGA) and longitudinal Zeeman background correction, and (3) a PE Model Z5100 AAS equipped with a HGA and transverse Zeeman background correction. We were able to transfer the method for serum Al previously established for the Z5100 and 4100ZL instruments to the 3110, with only minor modifications. As with the Zeeman instruments, matrix-matched calibration was not required for the 3110 and, thus, aqueous calibration standards were used. However, the 309.3-nm line was chosen for analysis on the 3110 due to failure of the continuum background correction system at the 396.2-nm line. A small, seemingly insignificant overcorrection error was observed in the background channel on the 3110 instrument at the 309.3-nm line. On the 4100ZL, signal oscillation was observed in the atomization profile. The sensitivity, or characteristic mass (m 0), for Al at the 309.3-nm line on the 3110 AAS was found to be 12.1±0.6 pg, compared to 16.1±0.7 pg for the Z5100, and 23.3±1.3 pg for the 4100ZL at the 396.2-nm line. However, the instrumental detection limits (3 SD) for Al were very similar: 3.0, 3.2, and 4.1 μg L−1 for the Z5100, 4100ZL, and 3110, respectively. Serum Al method detection limits (3 SD) were 9.8, 6.9, and 7.3 μg L−1, respectively. Accuracy was assessed using archived serum (and plasma) reference materials from various external quality assessment schemes (EQAS). Values found with all three instruments were within the acceptable EQAS ranges. The data indicate that relatively modest ETAAS instrumentation equipped with continuum background correction is adequate for routine serum Al monitoring. [Copyright &y& Elsevier]

Rhodium (Rh) was investigated as a permanent modifier for the atomization of Pb from biological fluids in W-filament atomic absorption spectrometry (AAS). Heating the W-filament with a Rh solution provided a protective coating for subsequent determinations of Pb in blood and urine matrices. The W-filament AAS instrumentation used was based on a prototype design that utilized self-reversal background correction scheme and peak area measurements. We found that Rh not only stabilized Pb during the pyrolysis step, but also facilitated the removal of carbonaceous residues during the cleaning step, requiring much less power than with phosphate modifier. Thus, the filament lifetime was greatly extended to over 300 firings. Periodic reconditioning with Rh was necessary every 30 firings or so. Conditioning the filament with Rh also permitted direct calibration using simple aqueous Pb standards. The method detection limit for blood Pb was approximately 1.5 μg dl−1, similar to that reported previously. Potential interferences from concomitants such as Na, K, Ca and Mg were evaluated. Accuracy was verified using lead reference materials from the National Institute of Standards and Technology and the New York State Department of Health. Blood lead results below 40 μg dl−1 were within ±1 μg dl−1 of certified values, and within ±10% above 40 μg dl−1; within-run precision was ±10% or better. Additional validation was reported using proficiency test materials and human blood specimens. All blood lead results were within the acceptable limits established by regulatory authorities in the US. When measuring Pb in urine, sensitivity was reduced and matrix-matched calibration became necessary. The method of detection limit was 27 μg l−1 for urine Pb. Urine lead results were also validated using an acceptable range comparable to that established for blood lead by US regulatory agencies. [Copyright &y& Elsevier]

Objective: To investigate the relationship between secondhand tobacco smoke (SHS) exposure and neuromotor function in children. Study Design: We studied 404 children aged 7-9 years who were exposed to SHS and other environmental neurotoxicants. Parents reported smoking habits, and serum cotinine levels were measured in children to determine SHS exposure. The Halstead-Reitan Finger Oscillation Test, Purdue Grooved Pegboard Test-Kiddie version, and Bruininks-Oseretsky Test of Motor Proficiency 2-Short Form were used to assess neuromotor function. Multivariable regression models that accounted for potential confounders were used to evaluate the associations. Results: Approximately 50% of the children were exposed to SHS based on serum cotinine measures. Exposure to SHS was significantly associated with motor impairment in children, including diminished visuomotor coordination (P = .01), fine motor integration (P = .01), balance (P = .02), and strength (P = .04) after adjusting for exposures to lead and manganese, age, sex, body mass index, measures of parental cognitive abilities, parental education, and quality of home environment. Conclusion: SHS is a neurotoxicant that may be associated with impaired childhood neuromotor function. [ABSTRACT FROM AUTHOR]

Multiple trace elements have estrogen receptor activity, but the association of these elements with uterine leiomyoma has not been defined. A cohort of 473 women aged 18–44 undergoing surgery for benign gynecologic indications provided whole blood and urine specimens for trace element analysis, which was performed by inductively coupled plasma mass spectrometry. Twenty elements were analyzed in blood and 3 in urine. The surgeon documented whether fibroids were present. Geometric mean concentrations were compared between women with and without fibroids, and logistic regression models were generated to assess the impact of the concentration of each trace element on the odds of fibroids. In multivariate regressions, odds of a fibroid diagnosis were higher with increased whole blood cadmium (AOR 1.44, 95% CI 1.02, 2.04) and lead (AOR 1.31 95% CI 1.02, 1.69), and urine cobalt (AOR 1.31, 95% CI 1.02, 1.70). Urinary cadmium and lead were not related to fibroid diagnosis. Increased exposure to trace elements may contribute to fibroid growth, and fibroids may serve as a reservoir for these elements. Differences between urinary and whole blood findings merit further investigation, as urinary cadmium has been considered a superior marker of exposure. [ABSTRACT FROM AUTHOR]

Abstract: This cross-sectional pilot study was conducted to assess environmental exposures to toxic elements through seafood consumption, among infertile couples undergoing in vitro fertilization (IVF). Twenty-five women and 15 men completed a questionnaire, and provided biologic specimens for quantification of Hg, Pb, Cd, and As using ICP-MS. Consumption of ‘mollusks’ and ‘shellfish’ are associated with increased blood Hg. Other seafood consumption predicts blood Pb, and urine Cd and As. Though limited by small numbers and the cross-sectional design, these results suggest that consumption of specific seafood items increases exposure to toxic elements in couples undergoing IVF. [Copyright &y& Elsevier]

Abstract: 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 1Å 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. [Copyright &y& Elsevier]

Background Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM 2.5 ), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM 2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia. Methods We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM 2.5 concentrations in early (~ 11 weeks gestation) and late (~ 31 weeks gestation) pregnancy and collected outdoor PM 2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset ( n = 125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness. Results The overall geometric mean (GM) one-week outdoor PM 2.5 concentration was 47.9 μg/m 3 (95% CI: 44.6, 51.6 μg/m 3 ), with highest concentrations in winter (118.0 μg/m 3 ; 110.4, 126.2 μg/m 3 ). One-week indoor and outdoor PM 2.5 concentrations were correlated ( r = 0.69). Indoor PM 2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3 μg/m 3 (15.8, 18.8 μg/m 3 ) and 24.5 μg/m 3 (22.2, 27.0 μg/m 3 ), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure. Conclusions Portable HEPA filter air cleaners can lower indoor PM 2.5 concentrations and SHS exposures in highly polluted settings. [ABSTRACT FROM AUTHOR]

Environmental exposure to metals and metalloids is associated with pregnancy loss in some but not all studies. We assessed arsenic, cadmium, mercury, and lead concentrations in 501 couples upon trying for pregnancy and followed them throughout pregnancy to estimate the risk of incident pregnancy loss. Using Cox proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals (CIs) for pregnancy loss after covariate adjustment for each partner modeled individually then we jointly modeled both partners’ concentrations. Incidence of pregnancy loss was 28%. In individual partner models, the highest adjusted HRs were observed for female and male blood cadmium (HR = 1.08; CI 0.81, 1.44; HR = 1.09; 95% CI 0.84, 1.41, respectively). In couple based models, neither partner’s blood cadmium concentrations were associated with loss (HR = 1.01; 95% CI 0.75, 1.37; HR = 0.92; CI 0.68, 1.25, respectively). We observed no evidence of a significant relation between metal(loids) at these environmentally relevant concentrations and pregnancy loss. [ABSTRACT FROM AUTHOR]

The feasibility of measuring arsenic and selenium contents in a single nail clipping was investigated using a small-focus portable X-ray fluorescence (XRF) instrument with monochromatic excitation beams. Nail clipping phantoms supplemented with arsenic and selenium to produce materials with 0, 5, 10, 15, and 20 µg/g were used for calibration purposes. In total, 10 different clippings were analyzed at two different measurement positions. Energy spectra were fit with detection peaks for arsenic K α , selenium K α , arsenic K β , selenium K β , and bromine K α characteristic X-rays. Data analysis was performed under two distinct conditions of fitting constraint. Calibration lines were established from the amplitude of each of the arsenic and selenium peaks as a function of the elemental contents in the clippings. The slopes of the four calibration lines were consistent between the two conditions of analysis. The calculated minimum detection limit (MDL) of the method, when considering the K α peak only, ranged from 0.210±0.002 µg/g selenium under one condition of analysis to 0.777±0.009 µg/g selenium under another. Compared with previous portable XRF nail clipping studies, MDLs were substantially improved for both arsenic and selenium. The new measurement technique had the additional benefits of being short in duration (~3 min) and requiring only a single nail clipping. The mass of the individual clipping used did not appear to play a major role in signal strength, but positioning of the clipping is important. [ABSTRACT FROM AUTHOR]

Prenatal exposure to toxic metals is linked to numerous adverse birth and later-in-life outcomes. These outcomes are tied to disrupted biological processes in fetal-derived tissues including the placenta and umbilical cord yet the precise pathways are understudied in these target tissues. We set out to examine the relationship between metal concentrations in umbilical cord and altered gene expression networks in placental tissue. These novel relationships were investigated in a subset of the Extremely Low Gestational Age Newborn (ELGAN) cohort (n = 226). Prenatal exposure to 11 metals/metalloids was measured using inductively coupled plasma tandem-mass spectrometry (ICP-MS/MS) in cord tissue, ensuring passage through the placental barrier. RNA-sequencing was used to quantify >37,000 mRNA transcripts. Differentially expressed genes (DEGs) were identified with respect to each metal. Weighted gene co-expression analysis identified gene networks modulated by metals. Two innovative mixtures modeling techniques, namely principal components analysis and quantile-based g-computation, were employed to identify genes/gene networks associated with multi-metal exposure. Individually, lead was associated with the strongest genomic response of 191 DEGs. Joint lead and cadmium exposure was related to 657 DEGs, including DNA Methyl Transferase 1 (DNMT1). These genes were enriched for the Eukaryotic Initiation Factor 2 (EIF2) pathway. Four gene networks, each containing genes within a Nuclear Factor kappa-light-chain-enhancer of Activated B Cells (NF-kB) -mediated network, were significantly increased in average expression level in relation to increases in all metal concentrations. All four of these metal mixture-associated gene networks were negatively correlated with important predictors of neonatal health including birth weight, placenta weight, and fetal growth. Bringing together novel methodologies from epidemiological mixtures analyses and toxicogenomics, applied to a unique cohort of extremely preterm children, the present study highlighted critical genes and pathways in the placenta dysregulated by prenatal metal mixtures. These represent potential mechanisms underlying the developmental origins of metal-induced disease. [Display omitted] • 37,000+ placental genes evaluated in response to 11 cord tissue metal concentrations • Pb was associated with strongest genomic response in single-metals analysis • Pro-inflammatory pathways, EIF2 - and NF-kB , enriched in response to metal mixtures • Expression of DNMT1, IGF2BP1, IGFBP1 was associated with multi-metal exposure • Metal mixture-associated gene networks were correlated with birth weight [ABSTRACT FROM AUTHOR]

Data are lacking on the effect of low level prenatal lead exposure. We examined the change in blood lead from the second trimester until delivery and the association between maternal and cord blood lead and birth outcomes in 98 participants of the CANDLE birth cohort study. Mixed effects models were constructed to assess blood lead change over pregnancy and regression models were used to explore the relationship with cord blood lead, characteristics effecting maternal lead, birth weight and gestational age. Overall, the geometric mean maternal blood level was 0.43 μg/dL. Maternal blood lead at each time point was predictive of cord blood lead level. A 0.1 μg/dL increase in second trimester lead was associated with lower birth weight and pre-term birth. Maternal blood lead below 1 μg/dL behaves in a manner similar to lead at higher levels and is associated with a small decrease in birth weight and gestational age. [ABSTRACT FROM AUTHOR]

Abstract: Airborne manganese (Mn) exposure can result in neurotoxicity and postural instability in occupationally exposed workers, yet few studies have explored the association ambient exposure to Mn in children and postural stability. The goal of this study was to determine the association between Mn and lead (Pb) exposure, as measured by blood Pb, blood and hair Mn and time weighted distance (TWD) from a ferromanganese refinery, and postural stability in children. A subset of children ages 7–9years enrolled in the Marietta Community Actively Researching Exposure Study (CARES) were invited to participate. Postural balance was conducted on 55 children residing in Marietta, Ohio and the surrounding area. Samples of blood were collected and analyzed for Mn and Pb, and samples of hair were analyzed for Mn. Neuromotor performance was assessed using postural balance testing with a computer force platform system. Pearson correlations were calculated to identify key covariates. Associations between postural balance testing conditions and Mn and Pb exposure were estimated with linear regression analyses adjusting for gender, age, parent IQ, and parent age. Mean blood Mn was 10μg/L (SEM=0.36), mean blood Pb was 0.85μg/dL (SEM=0.05), and mean hair Mn was 0.76μg/g (SEM=0.16). Mean residential distance from the refinery was 11.5km (SEM=0.46). All three measures of Mn exposure were significantly associated with poor postural balance. In addition, low-level blood Pb was also negatively associated with balance outcomes. We conclude that Mn exposure and low-level blood Pb are significantly associated with poor postural balance. [Copyright &y& Elsevier]

Highlights: [•] 473 women were recruited into an operative cohort and 131 in a population cohort. [•] Twenty trace elements in urine and three in blood were quantified. [•] Diagnosis by surgical visualization in operative and MRI in population cohort. [•] Blood cadmium was associated with a reduced odds of endometriosis diagnosis. [•] Urinary chromium and copper reflected an increased odds of endometriosis diagnosis. [Copyright &y& Elsevier]

• Included 627 children between the ages of 2–5 from CHARGE, a case-control study. • Measured 44 environmental compounds and metabolites in urine. • Estimated risks of autism spectrum disorder (ASD) and developmental delay (DD). • Conducted a weighted quantile sum regression analysis and single chemical analyses. • Higher concentrations increased odds of ASD and DD compared to typical. To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). This study included 627 children between the ages of 2–5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately. Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics. [ABSTRACT FROM AUTHOR]

Between 2010 and 2015, the New York State Department of Health (NYSDOH) conducted a biomonitoring program to gather exposure data on Great Lakes contaminants among licensed anglers and Burmese refugees living in western New York who ate locally caught fish. Four hundred and nine adult licensed anglers and 206 adult Burmese refugees participated in this program. Participants provided blood and urine samples and completed a detailed questionnaire. Herein, we present blood metal levels (cadmium, lead, and total mercury) and serum persistent organic pollutant concentrations [polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyldichloroethylene (DDE), and trans-nonachlor]. Multiple linear regression was applied to investigate the associations between analyte concentrations and indicators of fish consumption (locally caught fish meals, store-bought fish meals, and consuming fish/shellfish in the past week). Licensed anglers consumed a median of 16 locally caught fish meals and 22 store-bought fish meals while Burmese refugees consumed a median of 106 locally caught fish meals and 104 store-bought fish/shellfish meals in the past year. Compared to the general U.S. adult population, licensed anglers had higher blood lead and mercury levels; and Burmese refuges had higher blood cadmium, lead, and mercury, and higher serum DDE levels. Eating more locally caught fish was associated with higher blood lead, blood mercury, and serum ∑PCBs concentrations among licensed anglers. Licensed anglers and Burmese refugees who reported fish/shellfish consumption in the past week had elevated blood mercury levels compared with those who reported no consumption. Among licensed anglers, eating more store-bought fish meals was also associated with higher blood mercury levels. As part of the program, NYSDOH staff provided fish advisory outreach and education to all participants on ways to reduce their exposures, make healthier choices of fish to eat, and waters to fish from. Overall, our findings on exposure levels and fish consumption provide information to support the development and implementation of exposure reduction public health actions. [ABSTRACT FROM AUTHOR]

Abstract: Low-level environmental exposure to Hg, Pb and Cd may interfere with pregnancy during in vitro fertilization (IVF). The aim of this study was to generate hypotheses concerning associations between background exposures and pregnancy. In modified Poisson regression models including 24 women and adjusted for urine Cd and creatinine, blood Pb, age, race and smoking, 1μg/L increases in blood Hg are associated with decreases of 35% (P =0.03) and 33% (P =0.01) in clinical and biochemical pregnancies, respectively. In alternate Poisson models including 26 women and adjusted for blood Pb, blood Hg, age, race and smoking, 1μg/L increases in blood Cd are associated with decreases of 94% (P =0.01) and 82% (P =0.04) in clinical and biochemical pregnancies, respectively. No effects are detected in 15 men, although inverse associations are suggested for urine cadmium and pregnancy. These data suggest that low-level, background exposures to Hg and Cd may interfere with pregnancy following IVF. [Copyright &y& Elsevier]

Abstract: Objective: A number of studies suggest that Pb exposure increases cardiovascular disease risk in humans. As a potential mechanism for this effect, we recently reported a significant association between early childhood Pb levels and cardiovascular response to acute stress. The current study considers the association between current Pb levels and the autonomic nervous system activation pattern underlying the cardiovascular response to stress in a new cohort of children. Methods: We assessed blood Pb levels as well as cardiovascular responses to acute stress in 9–11year old children (N =140). Sympathetic activation (measured with pre-ejection period) and parasympathetic activation (measured with high frequency heart rate variability) were also assessed. Results: In a sample with very low levels of blood Pb (M =1.01μg/dL), we found that increasing blood Pb was associated with coinhibition of sympathetic and parasympathetic activation in response to acute stress. In addition, increasing Pb levels were associated with the hemodynamic stress response pattern typical of coinhibition — significantly greater vascular resistance and reduced stroke volume and cardiac output. Conclusions: Blood Pb levels were associated with significant autonomic and cardiovascular dysregulation in response to acute psychological stress in children. Moreover, these effects were significant at Pb levels considered to be very low and notably well below the 10μg/dL, the Centers for Disease Control and Prevention definition of an elevated blood Pb level. The potential for autonomic dysregulation at levels of Pb typical for many US children would suggest potentially broad public health ramifications. [Copyright &y& Elsevier]

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 μg/dL (range<1. 0–21. 0 μg/dL). The geometric mean was 4. 74 μg/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 μg 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. [Copyright &y& Elsevier]

Abstract: A biomonitoring method for the determination of Pb, Cd, and Hg at background levels in whole blood by inductively coupled plasma-mass spectrometry is described. While this method was optimized for assessing Pb, Cd and Hg at environmental levels, it also proved suitable for assessing concentrations associated with occupational exposure. The method requires as little as 200 μl of blood that is diluted 1+49 for direct analysis in the inductively coupled plasma-mass spectrometer. Method performance is compared to well-established AAS methods. Initial method validation was accomplished using National Institute of Standards and Technology (NIST) Standard Reference Material 966, Toxic Metals in Bovine Blood. Method detection limits (3s) are 0.05 μg dl−1 for Pb, 0.09 μg l−1 for Cd; and 0.17 μg l−1 for Hg. Repeatability ranged from 1.4% to 2.8% for Pb; 3% to 10% for Cd; and 2.6% to 8.8% for Hg. In contrast, AAS method detection limits were 1 μg dl−1, 0.54 μg l−1, and 0.6 μg l−1, for Pb, Cd, and Hg, respectively. Further performance assessments were conducted over a 2-year period via participation in four international External Quality Assessment Schemes (EQAS) operated specifically for toxic metals in blood. This includes schemes operated by (a) the New York State Department of Health''s Wadsworth Center, Albany, NY, USA (b) L′Institut National de Santé Publique du Québec, Centre de Toxicologie du Québec, Canada, (c) Friedrich-Alexander University, Erlangen, Germany, and (d) the University of Surrey, Guildford, UK Trace Elements scheme. The EQAS data reflect analytical performance for blind samples analyzed independently by both inductively coupled plasma-mass spectrometry and AAS methods. [Copyright &y& Elsevier]

Abstract: 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 9½ year old children (N =122) having relatively low prenatal (cord) blood lead levels (M =1.98 μg/dL, SD =1.75) and low postnatal (early childhood) blood lead levels (M =4.62 μg/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 μg/dL threshold currently adopted by the CDC for deleterious effects. [Copyright &y& Elsevier]

Abstract: BALB/c mice were exposed to 0.1ppm 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±0.9μg/dL) and significantly lower between PND21 and PND42 (20.3±4.7μg/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 &#60;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 0.1ppm 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 (&#60;1n amount of DNA) testicular cells may be diagnostic of defective sperm function. Thus, an administered dose of 0.1ppm via drinking water ingestion by neonatal male BALB/c mice sufficient to produce PbB of 20–60mg/dL compromised reproductive function in these mice as adults. [Copyright &y& Elsevier]

A tungsten-rhodium coating (250 μg W+200 μg Rh) on the integrated platform of a transversely heated graphite atomizer (THGA) was used as a permanent chemical modifier for the direct determination of lead in whole blood by electrothermal atomic absorption spectrometry (ETAAS). Blood samples were diluted 1+9 with a diluent consisting of 0.2% v/v HNO3 and 0.5% v/v TritonX-100, and 12 μl of the diluted sample was deposited on the platform. With use of the W-Rh modifier, tube lifetime was improved by a factor of 2–3 when compared with a conventional NH4H2PO4 modifier. With a standard THGA tube, use of the W-Rh permanent modifier allows simple calibration with aqueous standard solutions for blood Pb measurement. However, matrix-matched calibration is still necessary when an end-capped THGA tube is used. The method detection limit (3σ) based on integrated absorbance measurements is 1.5 μg dl−1 (0.092 μmol 1−1) for the standard THGA and 1.0 μg dl−1 (0.048 μmol l−1) for the end-capped tube. Various blood-based certified reference materials and proficiency testing samples, certified for Pb, were analyzed for validation purposes. All results were well within the range considered acceptable. Analysis of human blood samples for blood Pb measurement provided additional validation data against an established blood Pb ETAAS method that uses phosphate modifier. [Copyright &y& Elsevier]

Ensuring harmonization of (ultra-)trace element measurements in non-traditional matrices is a particular analytical challenge that is highlighted in this work for seminal plasma as part of the developmental core at the Wadsworth Center Human Health Exposure Analysis Resource Targeted Laboratory. Seminal plasma was collected from 39 male partners of women undergoing in vitro fertilization and analyzed by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) following deproteinization with concentrated HNO3. Validation was accomplished using: 1) two aqueous NIST SRMs; 2) a seminal plasma QC pool, characterized via standard additions; 3) standard additions on a subset of samples; and 4) sample duplicates. Agreement with NIST certified or reference values were obtained to within ±15% for the SRMs, and agreement between aqueous calibration values and standard additions values agreed to within ±10-20% for all elements. Standard additions of seminal plasma samples revealed varying matrix effects for Cu and Cr that were not found for the pooled samples. Duplicate analyses agreed to within ±10-30% depending on element. A potential source of contamination in colloidal silica used for processing seminal plasma was identified that requires further study. Comparisons with literature indicate lack of consensus for As, Cd, Cr, Mn, Pb, and V content in seminal plasma. Further work is needed to improve harmonization of future studies. [ABSTRACT FROM AUTHOR]

A consortium of laboratories established under the Children's Health Exposure Analysis Resource (CHEAR) used a multifaceted quality assurance program to promote measurement harmonization for trace organics analyses of human biospecimens that included: (1) participation in external quality assurance (EQA)/proficiency testing (PT) programs; (2) analyses of a urine-based CHEAR common quality control (QC) pool with each analytical batch across all participating laboratories; (3) method validation against NIST Standard Reference Materials® (SRMs); and (4) analyses of blinded duplicates and other project-specific QC samples. The capability of five CHEAR laboratories in organic chemical analysis increased across the 4-year period, and performance in the external PT program improved over time - recent challenges reporting >90% analytes with satisfactory performance. The CHEAR QC pools were analyzed for several classes of organic chemicals including phthalate metabolites and environmental phenols by the participating laboratories with every batch of project samples, which provided a rich source of measurement data for the assessment of intra- and inter-laboratory variance. Within-laboratory and overall variabilities in measurements across laboratories were calculated for target chemicals in urine QC pools; the coefficient of variation (CV) was generally below 25% across batches, studies and laboratories and indicated acceptable analytical imprecision. The suite of organic chemicals analyzed in the CHEAR QC pool was broader than those reported for commercially available reference materials. The accuracy of each of the laboratories' methods was verified through the analysis of several NIST SRMs and was, for example, 97 ± 5.2% for environmental phenols and 95 ± 11% for phthalates. Analysis of blinded duplicate samples showed excellent agreement and reliability of measurements. The intra-class correlation coefficients (ICC) for phthalate metabolites analyzed in various batches across three CHEAR laboratories showed excellent reliability (typically >0.90). Overall, the multifaceted quality assurance protocols followed among the CHEAR laboratories ensured reliable and reproducible data quality for several classes of organic chemicals. Increased participation in external PT programs through inclusion of additional target analytes will further enhance the confidence in data quality. [ABSTRACT FROM AUTHOR]

Objective: Studies have shown that individual trace element levels might be associated with abnormal glycemic status, with implications for diabetes. Few studies have considered these trace elements as a mixture and their impact on gestational glucose levels. Comparing three statistical approaches, we assessed the associations between essential trace elements mixture and gestational glucose levels.Methods: We used data from 1720 women enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Fetal Growth Study, for whom trace element concentrations (zinc, selenium, copper, molybdenum) were measured by inductively coupled plasma mass spectrometry (ICP-MS) using plasma collected during the 1st trimester. Non-fasting glucose levels were measured during the gestational diabetes mellitus (GDM) screening test in the 2nd trimester. We applied (1) Bayesian Kernel Machine Regression (BKMR); (2) adaptive Least Absolute Shrinkage and Selection Operator (LASSO) in a mutually adjusted linear regression model; and (3) generalized additive models (GAMs) to evaluate the joint associations between trace elements mixture and glucose levels adjusting for potential confounders.Results: Using BKMR, we observed a mean 2.7 mg/dL higher glucose level for each interquartile increase of plasma copper (95% credible interval: 0.9, 4.5). The positive association between plasma copper and glucose levels was more pronounced at higher quartiles of zinc. Similar associations were detected using adaptive LASSO and GAM. In addition, results from adaptive LASSO and GAM suggested a super-additive interaction between molybdenum and selenium (both p-values = 0.04).Conclusion: Employing different statistical methods, we found consistent evidence of higher gestational glucose levels associated with higher copper and potential synergism between zinc and copper on glucose levels. [ABSTRACT FROM AUTHOR]

• Toenails may be useful for surveillance of children's lead exposure because the can be self-collected. • Information on utility of toenails as a biomarker of children's lead exposure is limited. • Blood and toenail lead were correlated in a cohort of 12 year old children from Cincinnati. • Blood lead was correlated with cognitive scores but toenail lead was not. This study sought to compare lead (Pb) concentrations in toenails and blood and to investigate the association of each biomarker with children's cognitive function. Toenails and whole blood samples were collected from 224 twelve-year-old children, and their full-scale intelligence quotient (FSIQ) was assessed using the Wechsler Intelligence Scale for Children–4th edition. Inductively coupled plasma-mass spectrometry was used to determine blood (BPb) and toenail (TPb) Pb concentrations. Log BPb and Log TPb were significantly correlated (r2 = 0.49, p < 0.001). In unadjusted analyses, both log-transformed BPb and TPb were significantly associated with decreased FSIQ, but BPb accounted for approximately quadruple the FSIQ scores' variability than log-transformed TPb (model R2 = 0.12 and R2 = 0.03, respectively). After adjusting for neighborhood deprivation, caregiver intelligence (assessed with the Wechsler Abbreviated Scale of Intelligence–2nd edition), and child BMI, BPb remained significantly associated with decreased FSIQ, while TPb did not (p = 0.16). These results suggest that while concentrations of Pb in blood and toenails are correlated, TPb does not predict cognitive outcomes at these exposure levels. With caution and in conjunction with BPb, TPb may be used as a population-based biomarker of Pb exposure. [ABSTRACT FROM AUTHOR]