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Pb in bone may serve as a biomarker for cumulative Pb dose over decades. We hypothesized that adult female bone Pb concentrations (BoPb) would be significantly associated with average childhood blood Pb levels (BlPb) in a birth cohort exposed to relatively high levels of Pb from Pb paint residues. 94 African American women with a mean age of 32.7 years were recruited from the Cincinnati Lead Study (CLS) cohort. Subjects were born to women residing where there had been a high incidence of childhood Pb poisoning. Biomarkers of Pb exposure were serial BlPb concentrations spanning the prenatal period to approximately 6.5 years of age. BoPb was assessed in the tibia using the McMaster 109Cd K-XRF fourth generation system. Covariates included nutritional variables related to bone health. BlPb concentrations began to rise around 6 months of age and declined at later ages. Study participants were obese with a mean Body Mass Index of 34.4 and suboptimal vitamin D status as indicated by a mean 25-OH-D of 18.5 ng/ml. Average tibia Pb was −2.0 ± 8.6 μgPb/g bone mineral. In multiple linear regression, there was no significant association between BoPb at approximately age 30 and childhood cumulative BlPb(CumBlPb). Collectively, BoPb of this group of subjects was not detectable. We suggest that the reason these subjects' BoPb did not reflect their early exposure was that a significantly smaller proportion of Pb body burden resides in bone in young children. As the child grows what Pb there was in bone is diluted and any remaining signal is weak. It has been claimed that BoPb in older children, adolescents, and adults can recapitulate historical exposure to Pb during earlier development; however, in some populations, BoPb at later ages may not be an adequate biomarker to capture childhood exposure to Pb. • Bone lead by K-XRF in young adults was not associated with childhood blood lead concentrations. • Adult Bone lead may not be adequate to recapitulate childhood exposure to lead. • Improvements in K-XRF for bone lead may lead to different results in future studies. [ABSTRACT FROM AUTHOR]

Childhood lead exposure interferes with brain maturation, which adversely impacts cognitive and behavioral development. Lower intelligence scores, impairments in decision making, and increased rates of delinquent and criminal behavior are adverse outcomes linked to childhood lead absorption. The present study examined the relationships between childhood blood lead concentrations, structural brain volume, and measures of adult criminality. We hypothesized that increased rates of criminal arrests in adulthood would be inversely correlated with regional gray and white matter volumes, especially prefrontal areas responsible for decision making and self-control. We obtained childhood blood lead histories and anatomical magnetic resonance imaging from a subset of the longitudinally followed birth cohort known as the Cincinnati Lead Study. Criminality data for cohort participants were extracted from public databases. Voxel based morphometry was used to examine spatial differences in regional gray and white matter volumes associated with childhood blood lead concentrations and measures of adult criminality, respectively. Conjunction analyses allowed for the exploratory evaluation of common regions of volume change. Childhood blood lead concentrations were inversely associated with gray and white matter volume in the frontal, parietal and temporal lobes. Gray matter volumes were also inversely associated with criminal arrests with key regions within the cingulate, precuneus, several frontal gyri and the supplementary motor area. Conjunction analyses identified regions in the anterior cingulate, frontal gray matter and supplementary motor area associated with childhood lead absorption and criminality. The results from this study suggest that reduced brain volumes in regions responsible for cognition and emotional regulation are associated with childhood lead exposure and criminal arrests. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are recognized neurotoxicants, but the extent to which PBDEs influence various domains of behavior in children is not fully understood. As such, we reviewed epidemiologic studies published to date to provide an overview of the current state of knowledge on PBDEs' potential role in behavioral development. We identified 19 epidemiologic studies reporting on associations of prenatal and childhood concentrations of PBDEs with behaviors assessed in children from 1 to 12 years, including executive function, attention, externalizing and internalizing behaviors, adaptive skills, and social behaviors/Autism Spectrum Disorder (ASD). While the mechanisms of PBDE neurotoxicity in humans are still not clearly elucidated, findings from this review indicate that PBDE exposure during fetal development is associated with impairments in executive function and poorer attentional control in children. Results from large prospective cohorts demonstrate that prenatal and postnatal PBDE exposure adversely impacts externalizing behavior ( e.g. , hyperactivity and conduct problems). Additional studies are needed to determine whether PBDEs are associated with internalizing problems, adaptive skills, and social behaviors/ASD in children. Future studies will help better understand the potential neurotoxic effects of PBDE exposures during adolescence, possible sex-dependent effects, and the impact of exposure to BDE-209 and alternative flame retardants. Future studies should also examine chemical mixtures to capture real-world exposures when examining PBDEs and their impact on various behavioral domains in the context of multiple chemical exposures. [ABSTRACT FROM AUTHOR]

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]

Toxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS' impact on cognitive abilities. To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations. We included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ± 3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS. Prenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores. We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years. • PFOS and PFHxS were not associated with Full Scale IQ (FSIQ) at 8 years. • Prenatal PFOA and PFNA were positively associated with working memory at 8 years. • Child sex modified prenatal PFOA associations, with higher FSIQ scores in females. • We observed higher scores on several WISC scales in males, but not in females. • Findings do not support that PFAS are adversely associated with cognitive function. [ABSTRACT FROM AUTHOR]

Background Prenatal polybrominated diphenyl ether (PBDE) exposure has been associated with decrements in IQ and increased attention deficit/hyperactivity disorder related behaviors in children; however, data are limited for the role of postnatal exposures. Objectives We investigated the association between a series of childhood PBDE concentrations and Full-Scale Intelligence Quotient (FSIQ) and externalizing problems at 8 years. Methods We used data from 208 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort. Child serum PBDEs were measured at 1, 2, 3, 5, and 8 years; missing serum PBDE concentrations were estimated via multiple imputation. The Wechsler Intelligence Scales for Children-IV and the Behavior Assessment System for Children-2 was used to assess intelligence and externalizing behavior, respectively, in children at 8 years. We used multiple informant models to estimate associations between repeated lipid-adjusted PBDEs and child neurobehavior and to test for windows of susceptibility. Results Postnatal exposure to PBDE congeners (− 28, − 47, − 99, − 100, and − 153) at multiple ages was inversely associated with FSIQ at 8 years. For instance, a 10-fold increase in BDE-153 concentrations at 2, 3, 5, and 8 years were all related to lower FSIQ at age 8 (β for 3 years: − 7.7-points, 95% CI − 12.5, − 2.9; β for 8 years: − 5.6-points, 95% CI − 10.8, − 0.4). Multiple PBDE congeners at 8 years were associated with increased hyperactivity and aggressive behaviors at 8 years. Conclusions Postnatal PBDE exposure was associated with decrements in FSIQ and increases in hyperactivity and aggressive behaviors. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are associated with impaired visual spatial abilities in toxicological studies, but no epidemiologic study has investigated PBDEs and visual spatial abilities in children. The Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003–2006, Cincinnati, OH), was used to examine prenatal and childhood PBDEs and visual spatial abilities in 199 children. PBDEs were measured at 16±3 weeks gestation and at 1, 2, 3, 5, and 8 years using gas chromatography/isotope dilution high-resolution mass spectrometry. We used the Virtual Morris Water Maze to measure visual spatial abilities at 8 years. In covariate-adjusted models, 10-fold increases in BDE-47, −99, and −100 at 5 years were associated with shorter completion times by 5.2 s (95% Confidence Interval [CI] −9.3, −1.1), 4.5 s (95% CI −8.1, −0.9), and 4.7 s (95% CI −9.0, −0.3), respectively. However, children with higher BDE-153 at 3 years had longer completion times (β=5.4 s, 95% CI −0.3, 11.1). Prenatal PBDEs were associated with improved visual spatial memory retention, with children spending a higher percentage of their search path in the correct quadrant. Child sex modified some associations between PBDEs and visual spatial learning. Longer path lengths were observed among males with increased BDE-47 at 2 and 3 years, while females had shorter paths. In conclusion, prenatal and postnatal BDE-28, −47, −99, and −100 at 5 and 8 years were associated with improved visual spatial abilities, whereas a pattern of impairments in visual spatial learning was noted with early childhood BDE-153 concentrations. [ABSTRACT FROM AUTHOR]

Executive function is a critical behavioral trait rarely studied in relation to potential neurotoxicants. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) has been associated with adverse neurodevelopment, but there is limited research on executive function. Data from 256 mother–child pairs in the Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003–2006, Cincinnati, OH), was used to examine maternal serum PBDEs and PFASs and executive function in children ages 5 and 8 years. Maternal serum PBDEs and PFASs were measured at 16±3 weeks gestation. Executive function was assessed with the parent-rated Behavior Rating Inventory of Executive Function (BRIEF), which yields composite measures: behavioral regulation index, metacognition index, and global executive composite. Higher BRIEF scores indicate executive function impairments. Linear mixed models and generalized estimating equations were used to estimate covariate-adjusted associations between PBDEs and PFASs and executive function. A 10-fold increase in BDE-153 was associated with poorer behavior regulation ( β =3.23, 95% CI 0.60, 5.86). Higher odds of having a score ≥60 in behavior regulation (OR=3.92, 95% CI 1.76, 8.73) or global executive functioning (OR=2.34, 95% CI 1.05, 5.23) was observed with increased BDE-153. Each ln-unit increase in perfluorooctane sulfonate (PFOS) was associated with poorer behavior regulation ( β =3.14, 95% CI 0.68, 5.61), metacognition ( β =3.10, 95% CI 0.62, 5.58), and global executive functioning ( β =3.38, 95% CI 0.86, 5.90). However, no association was observed between perfluorooctanoate (PFOA) and executive function. Prenatal exposures to BDE-153 and PFOS may be associated with executive function deficits in school-age children. [ABSTRACT FROM AUTHOR]

Abstract: Antisocial behavior is a product of multiple interacting sociohereditary variables, yet there is increasing evidence that metal exposure, particularly, manganese and lead, play a role in its epigenesis. Other metals, such as arsenic, cadmium, chromium, and mercury, and exposure to traffic-related air pollution, such as fine particulate matter (≤2.5μm) have been associated with neurological deficits, yet largely unexplored with respect to their relationship with delinquent behavior. The purpose of this study is to evaluate the ecological relationship between county-wide reported airborne emissions of air metals, particulate matter, and youth adjudicated for criminal activity. Metal exposure data were collected from the Environmental Protection Agency AirData. Population statistics were obtained from the United States Census 2000 and adjudication data was obtained from the Courts of Common Pleases from each Ohio County. Simple correlations were calculated with the percentage of adjudications, all covariates, and estimated metal air emissions. Separate negative binomial regression models for each pollutant were used to provide an estimated risk ratio of pollutant emissions on the risk of adjudication for all Ohio counties adjusting for urban–rural residence, percentage of African Americans, median family income, percentage of family below poverty, percentage of high school graduation in 25 years and older populations, and population density. Metal emissions and PM in 1999 were all correlated with adjudication rate (2003–2005 average). Metal emissions were associated with slightly higher risk of adjudication, with about 3–4% increased risk per natural log unit of metal emission except chromium. The associations achieved statistical significance for manganese and mercury. The particulate matter ≤2.5 and ≤10μm emissions had a higher risk estimate, with 12% and 19% increase per natural log unit emission, respectively, and also achieved statistical significance. In summary, airborne exposure to manganese, mercury, and particulate matter are associated with increased risk of adjudication. Causality cannot be proven in observational studies such as this one, but the association warrants further examination in other research studies. Comprehensive epidemiologic investigations of metal exposure in pediatric populations should include social health outcomes, including measures of delinquent or criminal activity. Furthermore, the influence of metals on the neurotoxic pathway leading to delinquent activity should be further explored. [Copyright &y& Elsevier]

Abstract: Background: Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. Objectives: The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. Methods: We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. Results: The median total serum BDE concentration was 44.7ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. Conclusion: These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche. [Copyright &y& Elsevier]

It is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior. To examine the potential associations between Cd exposure during pregnancy and neurobehavior among children. We used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior. We categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: < limit of detection (LOD), Group 2: 0.06-0.22 μg/g creatinine, Group 3: ＞0.22 μg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years. No significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1–8 years of age in this study. • Low levels of prenatal cadmium exposure were found in maternal urine • Repeated neurobehavioral assessments were conducted between age 1–8 years • Maternal urinary cadmium was not adversely associated with child cognitive function • Prenatal cadmium exposure was not adversely associated with behavioral measurements [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks' gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5–2.3 μg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75–0.99 μg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72–0.97 μg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25–0.28 μg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (r s : 0.23–0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16–0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility. • House dust is considered a major source of organophosphate ester (OPE) exposure. • We measured urinary OPE metabolites in pregnant women at three timepoints. • Intraclass correlations between measurement timepoints were poor. • Non-white race was associated with lower OPE metabolite concentrations. • House dust OPEs and household size were associated with urinary OPE metabolites. [ABSTRACT FROM AUTHOR]