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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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: 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., Objective: To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations., Methods: 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., Results: 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., Conclusion: We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Childhood lead exposure is associated with neurobehavioral deficits. The effect of a residential lead hazard intervention on blood lead concentrations and neurobehavioral development remains unknown., Objective: To determine whether a comprehensive residential lead-exposure reduction intervention completed during pregnancy could decrease residential dust lead loadings, prevent elevated blood lead concentrations, and improve childhood neurobehavioral outcomes., Design, Setting, and Participants: This longitudinal, community-based randomized clinical trial of pregnant women and their children, the Health Outcomes and Measures of the Environment (HOME) Study, was conducted between March 1, 2003, and January 31, 2006. Pregnant women attending 1 of 9 prenatal care clinics affiliated with 3 hospitals in the Cincinnati, Ohio, metropolitan area were recruited. Of the 1263 eligible women, 468 (37.0%) agreed to participate and 355 women (75.8%) were randomized in this intention-to-treat analysis. Participants were randomly assigned to receive 1 of 2 interventions designed to reduce residential lead or injury hazards. Follow-up on children took place at 1, 2, 3, 4, 5, and 8 years of age. Data analysis was performed from September 2, 2017, to May 6, 2018., Main Outcomes and Measures: Residential dust lead loadings were measured at baseline and when children were 1 and 2 years of age. At 1, 2, 3, 4, 5, and 8 years of age, the children's blood lead concentrations as well as behavior, cognition, and executive functions were assessed., Results: Of the 355 women randomized, 174 (49.0%) were assigned to the intervention group (mean [SD] age at delivery, 30.1 (5.5) years; 119 [68.3%] self-identified as non-Hispanic white) and 181 (50.9%) to the control group (mean [SD] age at delivery, 29.2 [5.7] years; 123 [67.9%] self-identified as non-Hispanic white). The intervention reduced the dust lead loadings for the floor (24%; 95% CI, -43% to 1%), windowsill (40%; 95% CI, -60% to -11%), and window trough (47%; 95% CI, -68% to -10%) surfaces. The intervention did not statistically significantly reduce childhood blood lead concentrations (-6%; 95% CI, -17% to 6%; P = .29). Neurobehavioral test scores were not statistically different between children in the intervention group than those in the control group except for a reduction in anxiety scores in the intervention group (β = -1.6; 95% CI, -3.2 to -0.1; P = .04)., Conclusions and Relevance: Residential lead exposures, as well as blood lead concentrations in non-Hispanic black children, were reduced through a comprehensive lead-hazard intervention without elevating the lead body burden. However, this decrease did not result in substantive neurobehavioral improvements in children., Trial Registration: ClinicalTrials.gov identifier: NCT00129324.

Background: Toxicological studies highlight the potential neurotoxicity of perfluoroalkyl substances (PFAS) during fetal development. However, few epidemiological studies have examined the impact of childhood PFAS on neurodevelopment., Methods: We employed data from 208 children in the Health Outcomes and Measures of the Environment Study, a birth cohort (Cincinnati, OH), to examine associations of six serum PFAS concentrations measured at 3 and 8 years with executive function assessed at 8 years using the validated parent-completed Behavior Rating Inventory of Executive Function survey. We used multiple informant models to identify susceptible windows of neurotoxicity to PFAS and executive function. We investigated trajectories of PFAS concentrations and whether sex modified these associations., Results: Each ln-increase in perfluorononanoate (PFNA) at 8 years was associated with a 3.4-point increase (95% CI 0.4, 6.3) in metacognition score, indicating poorer function. Children with PFNA above the median at 8 years had poorer global executive functioning compared to children with concentrations consistently below median levels (β = 6.5, 95% CI 0.2, 12.9). Higher concurrent PFNA was associated with poorer behavior regulation among males, while associations among females were null (p PFNA×sex  = 0.018). Children with higher concurrent perfluorooctanoate (PFOA) had increased odds of being at risk of having clinical impairments in metacognition (OR = 3.18, 95% CI 1.17, 8.60). There were no associations between perfluorooctane sulfonate and perfluorohexane sulfonate and executive function., Conclusions: PFNA and PFOA at 8 years, but not 3 years, may be related to poorer executive function at 8 years. Results need to be confirmed in cohort studies with larger sample sizes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: East Liverpool, Ohio, the site of a hazardous waste incinerator and a manganese (Mn) processor, has had air Mn concentrations exceeding United States Environmental Protection Agency reference levels for over a decade. Save Our County, Inc., a community organization, was formed to address community environmental health concerns related to local industry. Researchers from the University of Cincinnati partnered with Save Our County to determine if air Mn had an impact on the neurocognitive function of children in the community., Methods: Children 7-9 years of age from East Liverpool and its surrounding communities, were enrolled (N=106) in the Communities Actively Researching Exposure Study from between March 2013-June 2014. Blood and hair were analyzed for Mn and lead, and serum was analyzed for cotinine. We used linear regression to assess associations between biological measures and IQ subscale scores., Results: Geometric mean blood lead (n=67), blood Mn (n=66), hair Mn (n=98), and serum cotinine (n=69) concentrations were 1.13±1.96μg/dL, 10.06±1.30μg/L, and 360.22±2.17ng/g, 0.76±6.12μg/L respectively. After adjusting for potential confounders, hair Mn was negatively associated with Full Scale IQ., Conclusions: Hair Mn was negatively associated with child IQ scores. Community partners were instrumental in the conception and implementation of this study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Manganese (Mn) is both an essential micronutrient and potential neurotoxicant. This dual role underlies a growing body of literature demonstrating that Mn exhibits a biphasic dose-response relationship with neurocognitive outcomes. We reviewed recent epidemiologic studies from 2007 to 2016 that investigated the relationship between Mn exposure and cognitive outcomes across the lifespan: early life, school-aged children, and adulthood. In total, 27 research articles were included in this review: 12 pediatric and 15 adult studies (10 occupational and five environmental exposures). The majority of these studies provided evidence of the negative effects of Mn exposure on cognition. The pediatric literature provides evidence that both high and low levels of Mn are negatively associated with intellectual development. Future Mn research should include examination of non-linear relationships and multiple neurotoxicants across the lifespan and particularly during critical developmental windows.

Background: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk., Objectives: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development., Methods: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression., Results: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = -0.0014; 95% CI: -0.0023, -0.0005, p = 0.002), stronger in males (β = -0.0024; 95% CI: -0.0038, -0.0009, p = 0.003) than in females (β = -0.0009; 95% CI: -0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = -0.0013; 95% CI: -0.0023, -0.0003, p = 0.01) DMR methylation, but primarily in females, (β = -0.0017; 95% CI: -0.0029, -0.0006, p = 0.005) rather than in males, (β = -0.0004; 95% CI: -0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months., Conclusions: Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood., Citation: Li Y, Xie C, Murphy SK, Skaar D, Nye M, Vidal AC, Cecil KM, Dietrich KN, Puga A, Jirtle RL, Hoyo C. 2016. Lead exposure during early human development and DNA methylation of imprinted gene regulatory elements in adulthood. Environ Health Perspect 124:666-673; http://dx.doi.org/10.1289/ehp.1408577.

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.

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 (β -3.51; 95% CI: -6.64, -0.38) and hair Mn (β -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.

Objective: To investigate the relationship between secondhand tobacco smoke (SHS) exposure and neuromotor function in children., Study Design: We studied 404 children aged 7-9 years who were exposed to SHS and other environmental neurotoxicants. Parents reported smoking habits, and serum cotinine levels were measured in children to determine SHS exposure. The Halstead-Reitan Finger Oscillation Test, Purdue Grooved Pegboard Test-Kiddie version, and Bruininks-Oseretsky Test of Motor Proficiency 2-Short Form were used to assess neuromotor function. Multivariable regression models that accounted for potential confounders were used to evaluate the associations., Results: Approximately 50% of the children were exposed to SHS based on serum cotinine measures. Exposure to SHS was significantly associated with motor impairment in children, including diminished visuomotor coordination (P = .01), fine motor integration (P = .01), balance (P = .02), and strength (P = .04) after adjusting for exposures to lead and manganese, age, sex, body mass index, measures of parental cognitive abilities, parental education, and quality of home environment., Conclusion: SHS is a neurotoxicant that may be associated with impaired childhood neuromotor function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The most common route for general population exposure to methyl mercury (MeHg) is fish consumption. Recommendations to pregnant women about consuming fish contaminated with MeHg are also applied to children, but there are few studies available about the effects of low-level postnatal MeHg exposure in them., Objectives: To investigate the association between postnatal methyl mercury exposure and neuropsychological development in a study of children also exposed to lead, both measured at 7 years., Methods: We measured MeHg concentrations in blood samples from the Treatment of Lead-Exposed Children (TLC) trial in which 780 children with elevated concentrations of lead in blood were followed with neuropsychological tests from ages 12-33 months through 7 years. Here we examine blood MeHg concentration and neuropsychological test scores, both measured at age 7 years. We used a maximum likelihood method to estimate geometric mean MeHg concentration and generalized linear regression models to analyze MeHg and neuropsychological test scores., Results: Geometric mean MeHg concentration was 0.56 (95% confidence interval: 0.52, 0.59) μ g/L. A 1  μ g/L increase in MeHg was associated with a 2.1 (95% confidence interval: 0.4, 3.8) point increase in Full-Scale IQ and 0.2 (95% confidence interval: 0.02, 0.4) point increase in Learning Slopeindex T-score on a test of verbal memory., Conclusions: Our results suggest that the relatively low MeHg exposure in US school-aged children from this population has no detectable adverse effect on neuropsychological development. The positive associations observed between MeHg and neurodevelopment may indirectly reflect consumption of beneficial polyunsaturated fatty acids from seafood.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: There is increasing concern about the potential effects of traffic-related air pollution (TRAP) on the developing brain. The impact of TRAP exposure on childhood behavior is not fully understood because of limited epidemiologic studies., Objective: We explored the association between early-life exposure to TRAP using a surrogate, elemental carbon attributed to traffic (ECAT), and attention deficit/hyperactivity disorder (ADHD) symptoms at 7 years of age., Methods: From the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort we collected data on exposure to ECAT during infancy and behavioral scores at 7 years of age. Children enrolled in CCAAPS had at least one atopic parent and a birth residence either < 400 m or > 1,500 m from a major highway. Children were followed from infancy through 7 years of age. ECAT exposure during the first year of life was estimated based on measurements from 27 air sampling sites and land use regression modeling. Parents completed the Behavioral Assessment System for Children, 2nd Edition, when the child was 7 years of age. ADHD-related symptoms were assessed using the Hyperactivity, Attention Problems, Aggression, Conduct Problems, and Atypicality subscales., Results: Exposure to the highest tertile of ECAT during the child's first year of life was significantly associated with Hyperactivity T-scores in the "at risk" range at 7 years of age, after adjustment [adjusted odds ratio (aOR) = 1.7; 95% CI: 1.0, 2.7]. Stratification by maternal education revealed a stronger association in children whose mothers had higher education (aOR = 2.3; 95% CI: 1.3, 4.1)., Conclusions: ECAT exposure during infancy was associated with higher Hyperactivity scores in children; this association was limited to children whose mothers had more than a high school education.

Background: Heavy metals, such as lead (Pb), mercury (Hg), and cadmium (Cd), are known toxicants, but their associations with the thyroid axis have not been well quantified at U.S. background levels., Objectives: We investigated the relationships between thyroid hormones (total and free thyroxine [TT4 and FT4], total and free triiodothyronine [TT3 and FT3], thyroid-stimulating hormone [TSH], and thyroglobulin [Tg]) and levels of Pb, Hg, and Cd in blood and Cd in urine., Methods: We separately analyzed a sample of 1,109 adolescents (12-19 years of age) and a sample of 4,409 adults from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007-2008. We estimated associations after adjusting for age, sex, race, urinary iodine, body mass index, and serum cotinine., Results: The geometric mean (GM) levels of blood Pb (BPb), total Hg, and Cd were 0.81 µg/dL, 0.47 µg/L, and 0.21 µg/L in adolescents and 1.43 µg/dL, 0.96 µg/L, and 0.38 µg/L in adults, respectively. The GMs of urinary Cd were 0.07 and 0.25 µg/g creatinine in adolescents and adults, respectively. No consistent pattern of metal and thyroid hormone associations was observed in adolescents. In adults, blood Hg was inversely related to TT4, TT3, and FT3 and urinary Cd was positively associated with TT4, TT3, FT3, and Tg, but there were no associations with Pb. Associations were relatively weak at an individual level, with about 1-4% change in thyroid hormones per interquartile range increase in Hg or Cd., Conclusions: Our analysis suggests an inverse association between Hg exposure and thyroid hormones, and a positive association between Cd exposure and thyroid hormones in adults.

Objectives: To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modified those associations., Methods: We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P)., Results: BPA was detected in >97% of the gestational (median: 2.0 μg/L) and childhood (median: 4.1 μg/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modified by child gender., Conclusions: In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the benefits of such reductions are unclear.

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 (≤2.5 μm) 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 ≤10 μm 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 © 2011. Published by Elsevier Inc.)

Objective: The purpose of this study was to examine the association of tobacco smoke and environmental lead exposure with conduct disorder (CD)., Methods: The National Health and Nutrition Examination Survey (NHANES) 2001-2004 is a nationally representative cross-sectional sample of the noninstitutionalized U.S. population. We examined the association of prenatal tobacco, postnatal tobacco, and environmental lead exposure with CD in children 8-15 years of age (n = 3,081). We measured prenatal tobacco exposure by parent report of cigarette use during pregnancy, and postnatal tobacco using serum cotinine levels. We assessed lead exposure using current blood lead concentration. Parents completed the Diagnostic Interview Schedule for Children to determine whether their children met criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV ) for CD., Results: Overall, 2.06% of children met DSM-IV criteria for CD in the past year, equivalent to 560,000 U.S. children 8-15 years of age. After adjustment, prenatal tobacco exposure was associated with increased odds for CD [odds ratio (OR) = 3.00; 95% confidence interval (CI), 1.36-6.63]. Increased blood lead levels (fourth vs. first quartile) and serum cotinine levels (fifth vs. first quintile) were associated with an 8.64-fold (95% CI, 1.87-40.04) and 9.15-fold (95% CI, 1.47-6.90) increased odds of meeting DSM-IV CD criteria. Increasing serum cotinine levels and blood lead levels were also associated with increased prevalence of CD symptoms (symptom count ratio, lead: 1.73; 95% CI, 1.23-2.43; symptom count ratio, cotinine: 1.97; 95% CI, 1.15-3.40)., Conclusions: These results suggest that prenatal tobacco exposure and environmental lead exposure contribute substantially to CD in U.S. children.

This study investigated the influence of succimer chelation therapy in eliminating and/or minimizing lead-associated impairments of motor functions such as postural balance and locomotion or gait activities. In this study, postural balance and functional locomotion or gait were quantitated in 161 children in Cincinnati enrolled in a randomized, placebo-controlled, double blind clinical trial. In comparison to the placebo group, the succimer therapy group showed significantly decreased postural sway during dynamic task performance implying improved postural balance. The results from locomotion tests demonstrated significant improvements in functional tasks of obstacle crossing and normal walking in the succimer treated group. While some beneficial neuromotor effects of succimer therapy were observed in the present study there remains several unanswered questions such as how long these effects will persist and how succimer therapy modifies lead-associated cerebellar deficits manifesting as perturbations in vestibular and/or proprioception systems for postural balance and functional locomotion.

Background: Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information., Objectives: The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration., Methods: Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33-month-olds with blood lead concentrations of 20 to 44 microg/dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study., Results: Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale-Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7., Conclusions: Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ.

This prospective study investigated the impact of early exposure to lead on the maturation of children's postural balance. The effect of lead exposure on age-associated maturation of postural balance was investigated on 91 children from the Cincinnati Lead Study (CLS) with a 5-year geometric mean lead concentration in blood of 11.66 microg/dL (range 3.89-28.33 microg/dL) by re-assessing their postural balance approximately every 20 months starting at mean age of 6.6 years through mean age of 12.1 years. The results presented in this paper provide evidence that low to moderate lead exposure in early childhood has a measurable and statistically significant impact on the maturation of postural balance. In comparison to less exposed children, of those in the higher lead group showed an impaired postural balance response. The results from this study suggest that children with early childhood lead exposure may need additional time to approach (or "catch up" with) their maturational postural balance status. As these subjects are now adults in their early to mid-twenties, poor postural balance may impact their daily living tasks and pose a higher risk of potential injuries at home and work.

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.

One hundred and ninety-five participants in the Cincinnati Lead Study were neuropsychologically evaluated in mid-adolescence. The neuropsychological measures yielded five factors labeled Memory, Learning/IQ, Attention, Visuoconstruction, and Fine-Motor. Prenatal, Average Childhood, and 78 month blood lead (PbB) levels were used in a series of multiple regression analyses. Following rigorous covariate pretesting and adjustment, a significant main effect of 78 month PbB on the Fine-Motor factor was found (p <.004). Significant interactions were also found between gender and lead exposure parameters for both Attention and Visuoconstruction indicating heightened risk in males. Finally, a trend toward significance was found for the PbB x SES interaction for Learning/IQ, consistent with previous evidence of increased educational and cognitive vulnerability for youth from more disadvantaged backgrounds. These results provide new evidence from the longest continuing prospective study of the remote effects of early lead exposure. They indicate the presence of selective neuropsychological effects in this population, and also that males and females are not uniformly affected. These results also underscore the complexity of models of neurobehavioral development, and the modest predictive power of any single determinant.

The effect of lead exposure on cognitive growth patterns was assessed in a longitudinal study of 196 children. Performances on tests of verbal comprehension and perceptual organization (Vocabulary & Block Design, Wechsler Intelligence Scales for Children) were measured at ages 6.5, 11 and 15 years. Growth curve analyses revealed that the quadratic model best described the relationship between test scores and age. Children with higher lead levels, as measured at age 15 years, demonstrated lower verbal comprehension scores over time and greater decline in their rate of Vocabulary development at age 15 years, as compared to children with lower lead levels. Lead exposure was not significantly associated with growth in perceptual organization test scores. Socioeconomic status and maternal intelligence were statistically significantly associated with growth patterns for both test scores, independent of the effects of lead. The findings suggest that lead negatively impacts the developmental progression of specific cognitive skills from childhood through adolescence.

Objective: In children, lead can cause serious permanent damage as a neurotoxicant. The objectives of the study were to evaluate potential exposure to lead-based paint in family housing units at a typical U.S. military installation and determine blood lead (PbB) levels in children ages 6 years or younger residing in these housing units., Methods: The authors conducted a risk assessment of 1,723 housing units and occupants at Fort Devens in Massachusetts. Data from the military dependent cohort was compared to estimates for the U.S. national population as reported from Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III)., Results: A total of 1992 individuals (1,009 males and 983 females) were screened for PbB, stratified into age groups, and separated into racial/ethnic categories. Four (0.3%) dust samples and 59 (11.6%) internal and 298 (77.8%) external paint chip samples contained hazardous levels of lead. The geometric mean PbB concentration for people ages 1 year and older reported by NHANES III was 2.8 micro g/dL, compared with 1.5 microg/dL for the military installation cohort (p<0.0001). PbB levels were higher for males than for females and higher for blacks than whites 6 years of age and older. Hispanics had lower PbB concentrations for all age groups except for those ages 1-2.9 years. Prevalence of PbB levels >10 microg/dL for all age groups was 1.6% in the military cohort, compared with 4.5% for the general population. For ages 1-2.9 years, no blacks or Hispanics and 0.6% of whites had PbB levels >10 micro g/dL, compared with 21.6% of blacks, 10.1% of Hispanics, and 8.5% of whites for the general population. For ages 3-5.99 years, 0.15% of blacks, 0% of Hispanics, and 0.3% of whites had PbB levels > or = 10 microg/dL, compared with 20.0% of blacks, 6.8% of Hispanics, and 3.7% of whites for the general population., Conclusion: Lead exposure for occupants of on-post military housing is much less than for those residing in the civilian sector.

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 (푛 = 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. OBJECTIVES: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. METHODS: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. RESULTS: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = -0.0014; 95% CI: -0.0023, -0.0005, p = 0.002), stronger in males (β = -0.0024; 95% CI: -0.0038, -0.0009, p = 0.003) than in females (β = -0.0009; 95% CI: -0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = -0.0013; 95% CI: -0.0023, -0.0003, p = 0.01) DMR methylation, but primarily in females, (β = -0.0017; 95% CI: -0.0029, -0.0006, p = 0.005) rather than in males, (β = -0.0004; 95% CI: -0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. CONCLUSIONS: Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review. DATA SOURCES: We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice. DATA EXTRACTION: We focused on the potential exposure to e-waste toxicants in vulnerable populations- that is, pregnant women and developing children-and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms. DATA SYNTHESIS: In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures. CONCLUSIONS: Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes. OBJECTIVE: We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults, determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure. METHODS: Adult participants from the Cincinnati Lead Study [n = 159; mean age (± SD), 20.8 ± 0.9 years] completed a quantitative, short-echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol, and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted. RESULTS: Mean childhood blood lead levels were associated with regionally specific brain metabolite concentrations adjusted for age at imaging and Full-Scale intelligence quotient. Adjusted analyses estimated for a unit (micrograms per deciliter) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter. CONCLUSIONS: Gray-matter NAA reductions associated with increasing childhood blood lead levels suggest that sustained childhood lead exposure produces an irreversible pattern of neuronal dysfunction, whereas associated white-matter choline declines indicate a permanent alteration to myelin architecture. [ABSTRACT FROM AUTHOR]

Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children's Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study's concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children's Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene-environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children's Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand. [ABSTRACT FROM AUTHOR]

Objective. Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 µg/dL (0.96-2.12 µmol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years. Methods. The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured... [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]

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]