Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

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.

An assessment of clinical laboratory performance for the determination of manganese in blood and urine.

BACKGROUND: Proficiency testing or external quality assessment schemes (PT/EQASs) are an important method of assessing laboratory performance. As each scheme establishes assigned values and acceptable ranges for the analyte according to its own criteria, monitoring of participant performance varies according to the scheme and can lead to conflicting conclusions. METHODS: Standard deviations (SDs) for PT were derived from Thompson's and biological variation models applied to blood and urine manganese (Mn) robust data from four EQASs from North America and Europe. The fitness for purpose was verified by applying these SDs to individual results. RESULTS: Using Thompson characteristic function the relationship between SD and Mn concentration, expressed in nmol/L was the square root of [19.72+(0.07712×Mn concentration2)] for blood and the square root of [6.772+(0.09852×Mn concentration2)] for urine. While the biological variation model was not suitable for urine, it produced an acceptable range for blood as ±54.4 nmol/L (assigned value ≤320 nmol/L) or 17% (assigned value >320 nmol/L). For blood, individual performance evaluated by the two approaches led to similar conclusions. CONCLUSIONS: The biological variation model can be used to propose quality specifications for blood, however it could not be applied to urine. The Thompson characteristic function model could be applied to derive quality specifications for Mn in urine and, to a lesser extent in blood. The more lenient quality specifications for blood highlight the difficulty of determining Mn in this matrix. Further work is needed to harmonize PT, such as using assigned ranges for the specimens.

Community Engagement and Data Disclosure in Environmental Health Research.

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 academic­community 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.

Evaluation of a New Optic-Enabled Portable XRF Instrument for Measuring Toxic Metals/Metalloids in Consumer Goods and Cultural Products.

X-ray fluorescence spectrometry (XRF) is a rapid, non-destructive multi-elemental analytical technique used for determining elemental contents ranging from percent down to the µg/g level. Although detection limits are much higher for XRF compared to other laboratory-based methods, such as inductively coupled plasma mass spectrometry (ICP-MS), ICP-optical emission spectrometry (OES) and atomic absorption spectrometry (AAS), its portability and ease of use make it a valuable tool, especially for field-based studies. A growing necessity to monitor human exposure to toxic metals and metalloids in consumer goods, cultural products, foods and other sample types while performing the analysis in situ has led to several important developments in portable XRF technology. In this study, a new portable XRF analyzer based on the use of doubly curved crystal optics (HD Mobile®) was evaluated for detecting toxic elements in foods, medicines, cosmetics and spices used in many Asian communities. Two models of the HD Mobile® (a pre-production and a final production unit) were investigated. Performance parameters including accuracy, precision and detection limits were characterized in a laboratory setting using certified reference materials (CRMs) and standard solutions. Bias estimates for key elements of public health significance such as As, Cd, Hg and Pb ranged from -10% to 11% for the pre-production, and -14% to 16% for the final production model. Five archived public health samples including herbal medicine products, ethnic spices and cosmetic products were analyzed using both XRF instruments. There was good agreement between the pre-production and final production models for the four key elements, such that the data were judged to be fit-for-purpose for the majority of samples analyzed. Detection of the four key elements of interest using the HD Mobile® was confirmed using archived samples for which ICP-OES data were available based on digested sample materials. The HD Mobile® XRF units were shown to be suitable for rapid screening of samples likely to be encountered in field based studies.

Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio, USA).

BACKGROUND: Manganese (Mn) plays a vital role in brain growth and development, yet excessive exposure can result in neurotoxicity. Marietta, Ohio, is home to the nation's longest-operating ferromanganese refinery, and community concern about exposure led to the development of the research study. OBJECTIVES: Our overall goal was to address the community's primary research question: "Does Mn affect cognitive development of children?" We evaluated the relationships between Mn exposure as measured by blood and hair Mn, along with other neurotoxicants including blood lead (Pb) and serum cotinine, and child cognition. METHODS: Children 7-9 years of age were enrolled (n = 404) in the Communities Actively Researching Exposure Study (CARES) from Marietta and Cambridge, Ohio, and their surrounding communities from October 2008 through March 2013. Blood and hair were analyzed for Mn and Pb, and serum was analyzed for cotinine. We used penalized splines to assess potential nonlinear associations between biological measures and IQ subscale scores, followed by multivariable regression models with categorical variables based on quartiles of the distribution for biological measures with nonlinear associations and continuous variables for biological measures with linear associations. RESULTS: Geometric mean blood (n = 327) and hair Mn (n = 370) concentrations were 9.67 ± 1.27 µg/L and 416.51 ± 2.44 ng/g, respectively. After adjusting for potential confounders, both low and high blood and hair Mn concentrations were associated with lower Full Scale IQ and subscale scores, with significant negative associations between the highest quartile and middle two quartiles of blood Mn (ß -3.51; 95% CI: -6.64, -0.38) and hair Mn (ß -3.66; 95% CI: -6.9, -0.43%) and Full Scale IQ. CONCLUSIONS: Both low and high Mn concentrations in blood and hair were negatively associated with child IQ scores. Serum cotinine was negatively associated with child cognitive function.

Childhood exposure to manganese and postural instability in children living near a ferromanganese refinery in Southeastern Ohio.

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 7-9 years 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 10 µg/L (SEM=0.36), mean blood Pb was 0.85 µg/dL (SEM=0.05), and mean hair Mn was 0.76 µg/g (SEM=0.16). Mean residential distance from the refinery was 11.5 km (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.

A comparison of clinical laboratory data for assigning a consensus value for manganese in a caprine blood reference material.

Biomonitoring for manganese (Mn) exposure is important due to its potential to cause adverse health effects. In this study, we investigate how different sample preparation methods (simple dilution, digestion, volumetric, gravimetric), calibration protocols (aqueous, blood-based, standard additions), and instrumental techniques affect Mn method bias and analytical imprecision. The techniques used included graphite furnace atomic absorption spectrometry (GFAAS), dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS), and sector field (SF-) ICP-MS. We analyzed NIST SRM 1643e Trace Elements in Water and SRM 1598a Inorganic Constituents in Animal Serum (both certified for Mn), and SRM 955c Toxic Metals in Caprine Blood - Level 1 (not certified for Mn). Various matrix effects in ICP-MS produced inaccurate results for SRM 1643e and discrepant results for SRM 955c. In the absence of a certified value for Mn in SRM 955c, we assigned a "consensus" value by combining data from the New York State Department of Health (NYS), the Centers for Disease Control and Prevention (CDC) and the Centre de toxicologie du Québec (CTQ). With this interlaboratory approach, we established an "all-lab" consensus value of 16.3 ± 0.8 µg L-1 based on data from DRC-ICP-MS with simple dilution sample preparation and blood-based calibration. We also assigned an "all-method" consensus value of 16.3 ± 0.9 µg L-1 based on GFAAS and SF-ICP-MS data from the NYS lab and the DRC-ICP-MS all-lab consensus value. Although the expanded uncertainty (U) calculated for the consensus values may not fully account for all sources of uncertainty, it does show the relative variation that might be expected from one study to the next for the determination of Mn in blood.

Occurrence of perchlorate in drinking water, groundwater, surface water and human saliva from India.

Perchlorate (ClO(4)(-)), which is used as an oxidizer in jet and rocket fuels, pyrotechnic devices and explosives, is a widespread contaminant in surface waters and groundwater of many countries. Perchlorate is known to affect thyroid function. Despite the compound's widespread occurrence and potential health effects, perchlorate levels in drinking water in India are not known. In this study, water samples collected from 13 locations in six states (n=66), and saliva samples collected from four locations in three states (n=74) in India, were analyzed for perchlorate using high performance liquid chromatography interfaced with tandem mass spectrometry (HPLC-MS/MS). Perchlorate was detected in most (76%) of the water samples analyzed at concentrations above the quantitation limit of 0.02 microg L(-1); concentrations ranged from <0.02 to 6.9 microg L(-1) (mean: 0.42+/-1.1 microg L(-1); median: 0.07 microg L(-1)). Mean concentrations of perchlorate in drinking water, groundwater, bottled water, surface water and rain water were 0.1, 1.0, <0.02, 0.05 and <0.02 microg L(-1), respectively. From a total of 66 water samples analyzed, only three samples contained perchlorate levels above 1 microg L(-1); all three were groundwater samples. Perchlorate was found in the saliva samples analyzed at concentrations above 0.2 microg L(-1) and up to 4.7 microg L(-1) (mean: 1.3+/-1.3 microg L(-1); median: 0.91 microug L(-1)). No remarkable differences in perchlorate concentrations were found among the sampling locations of water or saliva or in subgroups stratified by gender or age. Perchlorate concentrations in water samples from India are one to two orders of magnitude lower than the concentrations reported for the United States.