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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 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]

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]

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: 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: 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]

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]