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BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height--weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381, Introduction Manganese (Mn) is an element that exists ubiquitously in the environment, often in combination with other elements. (1) Mn plays a significant role in both human health and global [...]

Objectives: We assessed the extent of exposure to lead, cadmium, and mercury in the New York City (NYC) adult population. Methods: We measured blood metal concentrations in a representative sample [...]

Federal funding agencies increasingly support stakeholder participation in environmental health studies, and yet there is very little published research on engagement of community members in the development of data disclosure (DD) strategies. The Ohio Environmental Protection Agency reported airborne manganese (Mn) concentrations in East Liverpool, Ohio, 30 times higher than the reference concentration, which led to an academic-community research partnership to address community concern about Mn exposure, particularly among children. Children and their families were recruited to participate in a pilot study. Samples of blood and hair were collected from the children and analyzed for metals. DD mechanisms were developed using an iterative approach between community and academic partners. Individual DD letters were mailed to each participating family, and a community meeting was held. A post-meeting survey was administered to gauge community perception of the DD strategies. The purpose of this article is to demonstrate the effectiveness of engaging community partners in the conduct of environmental health research and in the development of DD strategies for individuals and the community at large. Scientists should include community partners in the development of DD strategies to enhance translation of the research findings and support the right of study participants to know their individual results., Introduction Federal funding agencies increasingly support stakeholder participation in environmental health research (NRC 2012; O'Fallon and Dearry 2002), as noted by the 2014 Institute of Medicine Roundtable (http://iom.nationalacademies.org/Activities/Environment/ EnvironmentalHealthRT/2014-MAR-19.aspx) on [...]

Zinc starvation in mycobacteria leads to remodeling of ribosomes, in which multiple ribosomal (r-) proteins containing the zincbinding CXXC motif are replaced by their motif-free paralogues, collectively called C− r-proteins. We previously reported that the 70S C− ribosome is exclusively targeted for hibernation by mycobacterial-specific protein Y (Mpy), which binds to the decoding center and stabilizes the ribosome in an inactive and drugresistant state. In this study, we delineate the conditions for ribosome remodeling and hibernation and provide further insight into how zinc depletion induces Mpy recruitment to C− ribosomes. Specifically, we show that ribosome hibernation in a batch culture is induced at an approximately two-fold lower cellular zinc concentration than remodeling. We further identify a growth phase in which the C− ribosome remains active, while its hibernation is inhibited by the caseinolytic protease (Clp) system in a zincdependent manner. The Clp protease system destabilizes a zincbound form of Mpy recruitment factor (Mrf), which is stabilized upon further depletion of zinc, presumably in a zinc-free form. Stabilized Mrf binds to the 30S subunit and recruits Mpy to the ribosome. Replenishment of zinc to cells harboring hibernating ribosomes restores Mrf instability and dissociates Mpy from the ribosome. Finally, we demonstrate zinc-responsive binding of Mpy to ribosomes in Mycobacterium tuberculosis (Mtb) and show Mpydependent antibiotic tolerance of Mtb in mouse lungs. Together, we propose that ribosome hibernation is a specific and conserved response to zinc depletion in both environmental and pathogenic mycobacteria. [ABSTRACT FROM AUTHOR]

Little information is available in the literature regarding trace element analysis of human follicular fluid. Most peer-reviewed publications offer few details about sample preparation, method development, or method validation. We have attempted to fill this gap in current knowledge by providing comprehensive details of our method development and validation process for the measurement of 24 trace elements (As, Ba, Be, Cd, Co, Cr, Cs, Cu, Hg, Mo, Mg, Mn, Pb, Pt, Rb, Se, Sb, Sn, Sr, Tl, U, V, W, Zn) in follicular fluid. A number of different sample preparation procedures were explored, with a goal of optimizing method detection limits (MDLs), for both quadrupole-inductively coupled plasma-mass spectrometry (Q-ICP-MS) and sector field (SF)-ICP-MS. Human follicular fluid samples (n = 72) were obtained from 64 women undergoing in vitro fertilization (IVF) treatment, and were successfully analyzed for 24 trace elements using SF-ICP-MS. [ABSTRACT FROM AUTHOR]

This is the second iteration of this review covering developments in ‘Atomic Spectrometry’. It covers atomic emission, absorption, fluorescence and mass spectrometry, but excludes material on speciation and coupled techniques which is included in a separate review. It should be read in conjunction with the other related reviews in the series.1-5 A critical approach to the selection of material has been adopted, with only novel developments in instrumentation, techniques and methodology being included. The major growth areas in evidence were the use of MC-ICP-MS as the method of choice for isotope ratio analyses, and new applications of AMS. The decline in the number of fundamental studies and developments in chemometrics continued. Some novel instrumental methods, such as the portable liquid electrode plasma, were reported and there were many new applications of solid phase extractants for on-line sample pretreatment, particularly using carbon nanotubes. [ABSTRACT FROM AUTHOR]

Prenatal mercury exposure and its fetotoxic effects may be of particular concern in urban immigrant communities as a result of possible contributing cultural factors. The most common source of exposure in these communities is ingestion of fish and shellfish contaminated with methylmercury. Other sources of exposure may occur in ritualistic practices associated with Hispanic and Caribbean-based religions. This study 1) assessed total mercury levels in both random urine specimens from pregnant women, and in cord blood; and 2) examined environmental sources of exposure from a convenience sample in a predominantly Caribbean immigrant population in Brooklyn, New York. A questionnaire designed in collaboration with health professionals from the Caribbean community assessed the frequency of fish consumption, ritualistic practices, occupational exposures, and use of dental amalgams and mercury-containing skin and household products. The geometric mean for total mercury in cord blood was 2.14 μg L−1 (95%CI: 1.76–2.60) (n = 78), and 0.45 μg L−1 (95%CI: 0.37–0.55) (n = 183) in maternal urine corrected for creatinine (μg g−1). Sixteen percent of cord blood mercury levels exceeded the estimated equivalent of U.S. Environmental Protection Agency's Reference Dose (5.8 μg L−1 blood). Predictors of cord blood mercury included maternal fish consumption and foreign birth of the mother. Predictors of urine mercury included foreign birth of the mother, number of dental amalgams, and special product use. There were no reports of mercury use in ritualistic practices or in cosmetics; however some women reported use of religious medals and charms. This study characterized risk factors for mercury exposure in a sample of urban, predominantly Caribbean-born blacks. Findings may help target interventions in this population, which might include appropriate fish selection and consumption frequency during pregnancy, and safe handling of mercury-containing products in the home. [ABSTRACT FROM AUTHOR]

A limited interlaboratory study for arsenic speciation analysis of whole blood was conducted in conjunction with the New York State Department of Health's (NYS DOH's) proficiency testing (PT) program for total arsenic in whole blood. Four laboratories were able to report values for up to five arsenic species in blood materials representing typical environmental concentrations. The arsenic species were very challenging to measure, due to the low concentrations (＜MDL―9.5 μg L−1). For most arsenic species, good agreement among the participants was observed and the consensus mean values obtained can be considered as the assigned target values for use as quality assurance materials in future analyses. [ABSTRACT FROM AUTHOR]

This is the third iteration of this review covering developments in ‘Atomic Spectrometry’. It covers atomic emission, absorption, fluorescence and mass spectrometry, but excludes material on speciation and coupled techniques which is included in a separate review.1It should be read in conjunction with the other related reviews in the series.2–5A critical approach to the selection of material has been adopted, with only novel developments in instrumentation, techniques and methodology being included. There have been few novel advances during the review period with the notable exception of the development of UV photochemical and electrochemical vapour generation methods; and miniaturisation of LIBS instrumentation for use in space exploration. [ABSTRACT FROM AUTHOR]

A method was developed to quantify five arsenic species (As(iii), As(v), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB)) in whole blood, using liquid chromatography (LC) coupled with inductively coupled plasma mass spectrometry (ICP-MS). The method can be used for routine monitoring of arsenic species in whole blood as well as in urine, but with different sample preparation. Whole blood was diluted 1 + 4 with reagents containing 3 mM HgCl2, which prevents As(iii) from binding to the LC column. The diluted blood was subjected to ultrafiltration so as to remove molecules larger than 3,000 Daltons. Analysis was completed within 12 min, for the determination of arsenic species in whole blood, and within 11 min in urine; the method detection limit is < 0.3 μg L−1for each arsenic species. The sum of arsenic species measured by the proposed method agreed well with assigned values for total arsenic in whole blood and urine reference materials, and in archived proficiency testing materials. Some urine reference materials provided additional information on the arsenic species present, and our testing results agreed well with the documented values. [ABSTRACT FROM AUTHOR]

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]

Background: A number of essential trace elements are involved in glucose metabolism, but the associations between these elements and glucose levels among pregnant women are unclear. Furthermore, little is known about the joint association of these trace elements. Methods: We used data from 1857 women enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Study, for whom trace element status (Zn, Se, Cu, Mo) was determined using plasma collected during the 1st trimester. Non-fasting glucose levels were measured during the GDM screening test. Three approaches were used to assess the joint effects of these trace elements on glucose levels. First, all four trace elements were included in a multivariable linear model and adaptive lasso was performed for model selection. Second, generalized additive models (GAMs) with model selection were fitted to allow non-linear associations. Lastly, a novel method, Bayesian Kernel Machine Regression (BKMR) was used to model the dose-response relationships of the trace element mixture in a non-parametric fashion. Results: In the multivariable linear model, we observed significant associations of glucose levels with plasma Cu (2.4 mg/dL increase per 1 SD increase on the log scale; 95% CI: 1.1, 3.7) and plasma Mo (-1.4 mg/dL decrease per 1 SD increase on the log scale; 95% CI: -2.6, -0.1). The GAM showed suggestive evidence of non-linear positive interaction between Zn and Cu in plasma (p-value = 0.052). Similar results were observed using the BKMR approach. Conclusion: Employing different statistical methods to study the effect of early pregnancy trace element mixtures on glucose levels, we found consistent evidences of hyperglycemic effect of Cu and hypoglycemic effect of Mo, as well as potential synergism between Zn and Cu. Future work is needed to better understand the joint effects of these elements in the context of the increasingly insulin-resistant state of pregnancy. Disclosure: Y. Zheng: None. C. Zhang: None. P.L. Williams: None. M. Weisskopf: None. P.J. Parsons: None. C.D. Palmer: None. G.M. Buck Louis: None. T. James-Todd: None. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Assessment of Prenatal Mercury Exposure in a Predominately Caribbean Immigrant Community in Brooklyn, NY" that was published in the September 06, 2012 issue is presented.

Heart disease is a leading cause of death in diabetic patients. There is growing evidence that dyslipidemia associated with diabetes contributes to the pathogenesis of diabetic cardiomyopathy, potentially through activation of protein kinase C (PKC) and/or angiotensin II (AII). This study was designed to determine whether elevated fatty acids produce cardiomyocyte mechanical dysfunction through PKC- or AII-dependent processes. Ventricular myocytes were isolated from non-diabetic and type 1 diabetic rats and cultured overnight in either normal medium or medium plus oleic acid (OA; 0.2mM). Subsets were supplemented with a non-specific PKC inhibitor bisindolylmaleimide (1µM) or angiotensin converting enzyme (ACE) inhibitor captopril (0.1µM). Isolated cardiomyocyte mechanical function was assessed using a video-based detection system. Myocyte relaxation was prolonged in non-diabetic cells cultured in OA (106 ± 3ms, n= 186) and in cells isolated from short-term (<1 week) diabetic animals (100 ± 5ms, n=55) when compared to controls (85 ± 2ms; n=164). Relaxation was normalized (OA treated myocytes) or reversed (diabetic cells) when cultured with either inhibitor. Conclusion: Fatty acid-induced cardiomyocyte dysfunction is preventable and diabetes-induced dysfunction is reversible by inhibiting cardiomyocyte derived PKC or ACE. [ABSTRACT FROM AUTHOR]

We have evidence that high glucose (HG) and high fatty acids (HFA) induce myocardial insulin resistance (IR), which mimic the effects of type 1 diabetes, and that IR is associated with abnormal excitation-contraction coupling (ECC). Although a direct link has yet to be determined, the hexosamine biosynthesis pathway (HBP) may play a central role. We have previously shown that non-specific PKC inhibition (in vitro) prevents HG-induced impaired ECC and insulin-stimulated glucose uptake in isolated cardiomyocytes, and reverses these dysfunctions in myocytes isolated from diabetic animals. We now show that inhibiting GFAT (rate limiting enzyme for the HBP), these HG effects are prevented, and the diabetes-induced abnormal ECC is reversed. For example, glucose uptake is blunted and myocyte relaxation is prolonged in HG cells by ∼30% of controls, and both are prevented by co-culture with azaserine (AZA). HFA also impairs glucose uptake and ECC. Strategies to inhibit HBP (with AZA or DON) or augment insulin sensitivity (with metformin) prevent HFA-induced abnormal ECC. Culturing cardiomyocytes from type 1 diabetic rats with DON also reverses abnormal ECC (e.g., myocyte relaxation is 2x slower in untreated diabetic myocytes than in normal cells). We suggest that the link between abnormal ECC and IR in each of our models (i.e., HG, HFA and diabetes) involves the HBP. ADA 7-04-RA-23 and N1H R01HL66895 (AJD) [ABSTRACT FROM AUTHOR]

Harmonization and traceability are related metrological principles that are indispensable to assuring measurement comparability across different biomonitoring studies. The Children's Health Exposure Analysis Resource (CHEAR) was established in 2015 with six laboratories providing environmental exposure measurements on biospecimens. To ensure harmonization across studies for trace elements, CHEAR used a multi-faceted approach that included: 1) an initial interlaboratory validation exercise based on the analysis of certified blood and urine reference materials; 2) frequent participation in an established interlaboratory proficiency program for trace elements; and 3) analysis of a common pool of well-characterized biological reference materials with each analytical batch. Method accuracy and precision were established for each laboratory via analysis of NIST SRM 955c Toxic Elements in Caprine Blood, SRM 2668 Toxic Elements in Frozen Human Urine and SRM 3668 Mercury, Perchlorate, and Iodide in Frozen Human Urine. The differences among the six laboratories for As, Cd, Hg, and Mn in urine and Cd, Hg, and Pb in whole blood were judged to be fit-for-purpose. Interlaboratory performance over a 5-year period demonstrated an improvement in performance, such that for 2018–2019, >99% of challenges for urine As, Cd, Hg, and Mn, and 95% for whole blood Cd, Hg, Pb, and Mn, were found to be satisfactory. The CHEAR common reference materials were analyzed by at least 5 laboratories for 22 elements in urine and 13–14 elements in whole blood, thus providing a rich source of data to assess intra- and inter-run performance. The suite of trace elements with assigned values in both blood and urine matrices are more comprehensive than similar reference materials from other sources, and is reflective of the concentrations necessary to support biomonitoring studies. While some areas for future improvement were identified, significant progress was made to improve harmonization of trace element measurements in biological matrices among the CHEAR network labs. • Harmonization challenges for trace element laboratories conducting biomonitoring. • Trace element proficiency testing program designed for biomonitoring laboratories. • Biomonitoring reference materials developed for trace elements in blood and urine. • Long term performance of trace element laboratories in biomonitoring studies. [ABSTRACT FROM AUTHOR]

Abstract Background Heightened blood lead levels (BLL) are associated with cognitive deficiencies and adverse behavioral outcomes. Lead-contaminated house dust is the primary source of exposure in U.S. children, and evidence suggests that even background (low-level) exposure has negative consequences. Identifying sources of background exposure is of great public health significance because of the larger number of children that can be affected. Methods Blood lead was assessed in a bi-racial sample of children from Syracuse, NY, aged 9–11, using established biomonitoring methods. The spatial density of vacant properties was modelled from publicly available georeferenced datasets. Further, regression models were used to measure the impact of this spatial density variable on children's BLL. Results In a sample of 221 children, with a mean BLL of 1.06 µg/dL (SD = 0.68), results showed increases in spatial density of vacant properties predict increases in median blood-PB levels, b = 0.14 (0.06–0.21), p <.001. This association held true even after accounting for demographic covariates, and age of individual housing. Further analysis showed spatial autocorrelation of the residuals changed from a clustered pattern to a random pattern once the spatial density variable was introduced to the model. Discussion This study is the first to identify a background-lead exposure source using spatial density modelling. As vacant properties deteriorate, lead-contaminated dust likely disperses into the surrounding environment. High-density areas have an accumulation of lead hazards in environmental media, namely soil and dust, putting more children at risk of exposure. Highlights • Spatial patterns of vacant properties contribute to low-level lead exposure. • Increases in spatial density predict increases in blood-lead. • This spatial process explains variation beyond known social determinants. [ABSTRACT FROM AUTHOR]

Objectives To assess changes in lead exposure in the New York City (NYC) adult population over a 10-year period and to contrast changes with national estimates, overall, and by socio-demographics and smoking status. Methods We used measurements of blood lead levels (BLLs) from NYC resident adults who participated in the NYC Health and Nutrition Examination Surveys (HANES) in 2004 and 2013–2014. We compared estimates of geometric means (GM), 95th percentiles, and prevalence of BLL ≥ 5 µg/dL overall and by subgroups over time, with adults who participated in the National HANES (NHANES) 2001–2004 and 2011–2014. Results The GM BLLs among NYC adults declined from 1.79 µg/dL in 2004 to 1.13 µg/dL in 2013–2014 (P < .0001). The declines over this period ranged from 30.1% to 43.2% across socio-demographic groups and smoking status (P < .0001 for all comparisons), and were slightly greater than declines observed nationally. The drop in prevalence of elevated BLLs (≥ 5 µg/dL) was also greater in NYC (4.8–0.5%), compared with NHANES (3.8–2.0%). By 2013–2014, NYC adults with lower annual family income (< $20,000) no longer had higher GM BLLs relative to those with higher incomes (≥ $75,000), a disparity improvement not observed nationally. Likewise, GM BLLs and 95th percentiles for non-Hispanic black adults in NYC were lower than GM BLLs for non-Hispanic white adults. Non-Hispanic Asian adults had the highest GM BLLs compared with other racial/ethnic groups, both in NYC in 2013–14 and nationally in 2011–2014 (1.37 µg/dL, P = .1048 and 1.22 µg/dL, P = .0004, respectively). Conclusion The lessening of disparity in lead exposure across income groups and decreasing exposure at the high end of the distribution among non-Hispanic black and Asian adults in NYC suggest that regulatory and outreach efforts have effectively targeted these higher exposure risk groups. However, Asian adults still had the highest average BLL, suggesting a need for enhanced outreach to this group. Local surveillance remains an important tool to monitor BLLs of local populations and to inform initiatives to reduce exposures in those at highest risk. [ABSTRACT FROM AUTHOR]

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]

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]

• 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: 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]

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 μg/dL, range 0.30 μg/dL – 6.64 μg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 μg/L, 360 ng/g, 0.974 μg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 μg/dL. • The effects surrounding concurrent exposure to manganese and lead remain unclear. • Joint Mn and Pb exposure may produce heightened neurocognitive impacts. • This association was observed when Mn was measured in hair and toenail samples. • Even at low blood Pb levels, the interactive effects of Mn and Pb are apparent. [ABSTRACT FROM AUTHOR]

Exposure to air pollution has been linked to individual health effects in occupational environments and communities proximate to air pollution sources. Use of estimated chemical concentrations from the Risk Screening Environmental Indicators (RSEI) model, derived from the Toxics Release Inventory, can help approximate some contributions to individual lifetime exposure to risk from air pollution and holds potential for linkages with specific health outcome data. Our objectives were: (1) use regression modeling to test for associations between observed blood metal concentrations in children and RSEI total air concentrations of the same metals released from proximate manufacturing facilities; (2) determine the relative contribution of RSEI air pollution to blood metal concentrations; and (3) examine associations between chronic metal exposure and cardiovascular functioning and structure in study participants. Using data synthesis methods and regression modeling we linked individual blood-based levels of lead, mercury, and cadmium(Pb, Hg, Cd) and cardiovascular functioning and structure to proximate industrial releases of the same metals captured by the Environmental Protection Agency's (EPA) RSEI geographic microdata. We found that RSEI-derived ground-level ambient air concentrations of Hg and Cd were a significant predictor of blood metal levels, when controlling for covariates and other exposure variables. In addition to associations with blood metal findings, RSEI concentrations also predicted cardiovascular dysfunction and risk including changes in left-ventricular mass, blood pressure, and heart rate. Right-to-know data, such as EPA's RSEI, can be linked to objective health outcomes, rather than simply serving as a non-specific risk estimate. These data can serve as a proxy for hazard exposure and should be used more widely to understand the dynamics of environmental exposure. Furthermore, since these data are both a product of and contribute to regulatory decision making, they could serve as an important link between disease risk and translation-orientated national environmental health policy. • Blood, Hg blood Cd levels are increased for children with chronic early life exposure to air pollution of the same metals. • Chronic Cd exposure among children may be causing deleterious impact on cardiovascular health potentially impacting future CVD risk. • Regulatory data for monitoring pollution levels are effective measures of spatial lifecourse exposure to air pollutants. [ABSTRACT FROM AUTHOR]

Initial interest in the adverse consequences of exposure to lead (Pb), mercury (Hg), and cadmium (Cd) focused on relatively high exposures through environmental or occupational sources; however, recent evidence suggests even low-level background exposure to non-essential metals might be detrimental, particularly for children's health and development. One potentially important source of increased background levels of non-essential toxic metals is diet. We considered whether differences in diet are associated with levels of non-essential metals in blood and whether racial differences in metals are mediated by dietary differences. We assessed blood levels of Pb, Hg, and Cd in a sample of 9–11 year-old children (N = 295) comprised of 42% European Americans (EAs), 58% African American (AAs), and 47% female. Diet was assessed using 24-h dietary recalls during phone interviews administered to parents on two consecutive days (Friday and Saturday). The Healthy Eating Index-2105 (HEI-2015) was calculated to assess diet quality. The current study identified significant dietary sources of non-essential metal exposure – namely total fruit for Pb, total protein for Hg, and greens and beans for Cd. Moreover, AAs were found to have significantly higher blood levels of Pb and Hg than EAs and these racial differences were significantly mediated by these dietary differences. This study is one of very few to consider total diet in children and exposure to the non-essential metals Pb, Hg, and Cd, and the first to demonstrate that racial differences in increased background blood levels of non-essential toxic metals can be accounted for by racial differences in diet. Given regional differences in food consumption patterns and specific farm and store sources for the foods, the generalizability of the current findings has yet to be determined; however, commonly consumed foods appear to be a significant source of low-level non-essential metals. • Even low-level background exposure to non-essential metals might be detrimental to children's health. • Dietary sources of non-essential toxic metals were identified in 9–11 year old children. • Significant sources of metals were total fruit for Pb, total protein for Hg, and greens and beans for Cd. Pb and Hg were higher in African American than Anglo American children and these differences were accounted for by diet. • Foods with high levels of toxicants may be less important than foods with lower levels but higher consumption. [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]

Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log 2 -transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log 2 -transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) μg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth. • Ulaanbaatar, Mongolia has poor air quality due primarily to coal smoke from home heating stoves. • Emissions from coal stoves may be an important source of cadmium exposure in this population. • Maternal blood cadmium concentrations were associated with lower birth weight. • In some settings, cadmium may play a role in the putative association between air pollution and fetal growth. [ABSTRACT FROM AUTHOR]

The New York State Department of Health conducted the Healthy Fishing Communities Program in collaboration with the Agency for Toxic Substances and Disease Registry to assess human exposure to contaminants common to Lake Ontario, Lake Erie and surrounding rivers and waterways among populations in western New York State who eat locally caught fish. The program enrolled licensed anglers and Burmese refugees and immigrants, living near four designated Great Lakes Areas of Concern: Buffalo River, Niagara River, Eighteenmile Creek, and the Rochester Embayment. These target populations were sampled and enrolled independently into the program between February and October of 2013. A core set of contaminants were measured in blood and urine of 409 licensed anglers and 206 Burmese refugees and immigrants which included lead, cadmium, mercury, PCBs, PBDEs, organochlorine pesticides (hexachlorobenzene, mirex, DDT, DDE, and chlordane and its metabolites oxychlordane and trans-Nonachlor), and PFOS and PFOA. Biomonitoring results showed that both groups had higher geometric means for blood lead, total blood mercury, and serum PFOS compared to the 2013–2014 NHANES reference levels. The Burmese refugee group also showed higher geometric means for creatinine-adjusted urine mercury and lipid-adjusted serum DDE compared to national levels. Licensed angler participants reported eating a median of 16 locally caught fish meals in the past year. Burmese participants consumed local fish throughout the year, and most frequently in the summer (median 39 fish meals or 3 times a week). The study results provide valuable information on populations at high risk of exposure to contaminants in the Great Lakes Basin of western New York. The results provide the foundation for developing and implementing public health actions to reduce potential exposures to Great Lakes pollutants. • Licensed anglers and Burmese refugees eat fish caught from western NY Great Lakes. • Both groups had elevated lead, mercury, and PFOS levels compared to NHANES. • Burmese refugee group also had elevated DDE levels. • Burmese refugee group was less aware of fish advisories than licensed anglers. [ABSTRACT FROM AUTHOR]

Context: Studies suggest many essential trace metal(loid)s are involved in glucose metabolism, but the associations among pregnant women are unclear., Objective: To assess associations between early pregnancy plasma zinc, selenium, copper, and molybdenum levels and blood glucose levels later in the second trimester., Design: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies‒Singleton Cohort is a prospective cohort study conducted between July 2009 and January 2013., Setting: Twelve academic research hospitals in the United States., Patients: A total of 1857 multiracial, nonobese, healthy women., Main Outcome Measure: Blood glucose levels from 1-hour 50-g gestational load test (GLT) at 24 to 28 weeks of gestation., Results: Higher concentrations of first-trimester copper were associated with higher glucose levels from the GLT (i.e., every 50% increase in copper concentration was related to 4.9 mg/dL higher glucose level; 95% CI: 2.2, 7.5 mg/dL) adjusted for maternal sociodemographic characteristics and reproductive history. In contrast, every 50% increase in molybdenum concentration was associated with 1.2 mg/dL lower mean glucose level (95% CI: -2.3, -0.1 mg/dL). The magnitude of these associations was greater at the upper tails of glucose level distribution based on quantile regressions of the 10th, 50th, and 90th percentiles., Conclusions: Higher copper and lower molybdenum concentrations could increase the risk of glucose dysregulation during pregnancy, with women at higher risk of gestational diabetes mellitus potentially affected to a greater extent. Further work is needed to understand the mechanisms involved with early pregnancy essential metal(loid)s to inform clinical diagnosis and prevention of glucose intolerance during pregnancy., (Copyright © 2019 Endocrine Society.)

[This corrects the article DOI: 10.1289/ehp.10056.].