2014 Progress Report: Center for Children’s Environmental Health and Disease Prevention Research (P01) (joint EPA and NIEHS) - CHAMACOS

EPA Grant Number: R834513
Center: Center for the Health Assessment of Mothers and Children of Salinas - UC Berkeley School of Public Health: CHAMACOS Office, Berkeley, CA
Center Director: Eskenazi, Brenda
Title: Center for Children’s Environmental Health and Disease Prevention Research (P01) (joint EPA and NIEHS) - CHAMACOS
Investigators: Eskenazi, Brenda , Arora, Manish , Barcellos, Lisa , Barlow, Janice , Bradman, Asa , Chevrier, Jonathan , Eisen, Ellen , Harley, Kim , Holland, Nina T. , Jerrett, Michael , Johnson, Caroline , Lustig, Robert , Minkler, Meredith , Molitor, John , Rosas, Lisa Goldman , Salvatore, Alicia , Sjodin, Andreas , Smith, Donald
Current Investigators: Eskenazi, Brenda , Arora, Manish , Barcellos, Lisa , Barlow, Janice , Blum, Arlene , Bradman, Asa , Crinella, Frank , Eisen, Ellen , Fenster, Laura , Harley, Kim , Harnly, Martha , Holland, Nina T. , Hubbard, Alan , Jerrett, Michael , Johnson, Caroline , Lustig, Robert , McKone, Thomas , Minkler, Meredith , Molitor, John , Rosas, Lisa Goldman , Salvatore, Alicia L. , Sjodin, Andreas , Smith, Donald , Wallerstein, Nina
Institution: University of California - Berkeley
EPA Project Officer: Louie, Nica
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2017)
Project Period Covered by this Report: June 1, 2013 through May 31,2014
Project Amount: $3,585,543
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

Project A: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty

Examine the association of DDT, Mn and PBDEs with neurodevelopment and onset of puberty in boys in the CHAMACOS cohort. This study directly addresses worldwide concerns that changes in onset of sexual maturation may be related to endocrine disruptors in the environment and fills a large data gap on boys. It also addresses concerns that exposure to DDT/E, PBDEs and Mn may compromise neurodevelopment.

Specific Aim 1: To maintain and expand the CHAMACOS cohort as children begin the critical transition to puberty, assessing neurodevelopment and pubertal development in 300 boys from 9 to 13 years of age.

Specific Aim 2: To determine whether prenatal and childhood exposure to DDT/E, PBDEs and Mn are associated with neurobehavioral functioning at age 9, 10.5 and 12 years.

Specific Aim 3: To determine whether prenatal and childhood exposure to DDT/E, PBDEs and Mn are associated with timing of pubertal development in boys between age 9 and 13 years.

Specific Aim 4: To determine whether prenatal and childhood exposure to DDT/E, PBDEs and Mn are associated with hormone levels in boys at age 12

Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

Examine novel methods of examining prenatal exposure to Mn, PBDE and DDT/E compounds. For exposure to Mn, we are measuring Mn levels in shed deciduous teeth and in hair collected when the children were 10.5 years of age. For PBDEs and DDT/E, we are developing models to back-extrapolate prenatal exposure levels from 9-year measured levels and other determinants of exposure.

Specific Aim 1: To measure Mn, PBDEs and DDT/E in shed deciduous teeth.

Specific Aim 2: To determine the relationship between Mn, PBDE and DDT/E levels in teeth with other relevant biological measures.

Specific Aim 3: To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth, hair and child blood.

Specific Aim 4: To identify population correlates of PBDEs and DDT/E exposure in 9-year-old boys

Project C: Epigenetics Project: Epigenetic Effects of DDT/E and PBDEs on Puberty

Investigate the effects of exposure on the epigenome and its relationship with pubertal onset.Specific Aim 1: To analyze global DNA methylation in newborn children by three different assays

Specific Aim 1: To analyze global DNA methylation in newborn children by three different assays.

Specific Aim 2: To determine ontogenetic changes in global DNA methylation in blood of children between birth and 12 years.

Specific Aim 3: To investigate the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global DNA methylation.

Specific Aim 4: To determine whether global methylation is associated with onset of puberty and hormonal changes.

Biorepository Core

Ensure that all environmental and biological specimens are collected, managed and stored so as to maximize their future utility.

Community Outreach and Translation Core (COTC)

Enable Center scientists and community partners to communicate study findings in a culturally appropriate manner, raise awareness of children’s environmental health within and beyond the Salinas Valley, and support policies that will improve the health of low-income Latino residents locally in Monterey County and throughout the state and nation.

Specific Aim 1: To disseminate Center research findings to study participants, the Salinas Valley community and other stakeholders.

Specific Aim 2. To increase awareness about children’s environmental health among low-income Latino communities, clinicians, and service providers through widespread dissemination of innovative outreach and educational programs.

Specific Aim 3: To build the capacity of Salinas Valley youth to promote healthy environmental policies in their community.

Specific Aim 4: To educate policy makers at the local, state and national levels about Center research findings and children’s environmental health priorities.

Progress Summary:

Project A: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty

Specific Aim 1: To maintain and expand the CHAMACOS cohort as children begin the critical transition to puberty, assessing neurodevelopment and pubertal development in 300 boys from 9 to 13 years of age.

Specific Aim 2: To determine whether prenatal and childhood exposure to DDT/E, PBDEs and Mn are associated with neurobehavioral functioning at age 9, 10.5 and 12 years.

We have successfully met our goal of expanding the CHAMACOS cohort to 300 boys. We assessed 319 boys at age 9 years and 309 boys at age 10.5. To date, 287 boys have been assessed at age 12, and we are on track to complete visits with at least 300 boys by September 2014. We are approximately halfway through the final visit point of this project, with 160 boys assessed to date at age 12.75.

DDT/E: To increase statistical power, we combined boys and girls from the CHAMACOS cohort in all analyses of neurodevelopment, after confirming that there was no heterogeneity in associations by sex. For CHAM1 (the original CHAMACOS cohort followed since in utero), prenatal DDT/E concentrations were measured in maternal serum collected during pregnancy. For CHAM2 (participants enrolled at age 9), prenatal DDT/E concentrations were back-extrapolated from DDT/E levels measured in maternal serum collected when the child was 9 years old using the SuperLearner algorithm, which is an ensemble machine learning technique that uses the weighted combination of algorithms to return a prediction function that minimizes the cross-validated mean squared error.

Multivariable linear models and generalized estimating equation (GEE) models were used to test the relationship between prenatal p,p’-DDT/E serum concentrations with full scale IQ and four subtests (working memory, perceptual reasoning, verbal comprehension and processing speed) assessed at the 7-year (CHAM1 only) and 10.5 -year (CHAM1 and CHAM2) visits. No significant associations were seen between prenatal p,p’-DDT/E and IQ or any of the four subtests when age 7 (n = 316) and 10.5 (n = 595) outcomes were examined individually. However, as shown in Table 1, the longitudinal GEE analysis (n = 619) found a significant decrease in processing speed for every tenfold increase in prenatal p,p’-DDT (β = -1.6, CI 95% = -2.9,-0.3) and p,p’-DDE (β = -2.0, CI 95% = -3.7,-0.3) serum concentrations.

Table 1. Change in cognitive scores in children tested at 7 years and/or 10.5 years for each 10-fold increase in prenatal p,p’-DDT/E using GEE modelsa

 

PBDEs: As with DDT, measured prenatal PBDE concentrations were used for CHAM1 children and back-extrapolated prenatal concentrations were used for CHAM2 children. Measured PBDE concentrations at age 9 were available for both CHAM1 and CHAM2 children. Prenatal and 9-year PBDE concentrations were associated with decrements in memory at 9 and 10.5 years. Each tenfold increase in prenatal ΣPBDE concentrations was associated with decrements in scores on the NEPSY-II Memory for Designs test at age 9 (β = -0.6, p = 0.22 for immediate recall; β = -1.1, p = 0.04 for delayed recall) and each tenfold increase in 9-year ΣPBDE concentrations was associated with lower scores on the California Auditory Verbal Learning Task (CAVLT) at age 10.5 (β = -4.8, p = 0.04 for immediate recall; β = -3.9, p = 0.06 for delayed recall). Nonsignificant decrements were seen in WISC full scale IQ and subscales at age 10.5.

DDT/E and PBDEs: We found evidence of interaction between prenatal DDT/E and PBDEs on child behavior. Maternal DDT/E appeared to potentiate the association of PBDEs and teacher report of internalizing problems (βInter = 4.9; 95% CI = 0.8, 9.1), particularly for anxiety (βInter = 4.5; 95% CI = 0.4, 8.7) and somatization (βInter = 6.7; 95% CI = 2.1, 11.3). For instance, maternal PBDE concentrations were associated with an 8.2-point (95% CI: 0.4, 16.1) increase in scores on the BASC somatization problems scale at the 95th percentile of maternal DDT but no significant association was observed at the 50th percentile of maternal DDT (β = -4.6; 95% CI = -9.2, 0.1; Figure 1). We found no evidence of interaction for postnatal exposure.

Figure 1. Teacher report of somatization problems and interaction between prenatal DDT and PBDEs.

Mn: We measured prenatal and postnatal dentine Mn concentrations in shed teeth. We examined the relationship between prenatal and postnatal exposure and children’s performance at 6, 12 and 24 months of age on the Bayley Scales of Infant Development mental and psychomotor development indices. We explored the possibility of an inverted U-shaped association with neurodevelopment because Mn is an essential nutrient. We also evaluated potential interactions between Mn exposure and blood lead concentrations as well as maternal iron status during pregnancy. We observed a negative association between postnatal Mn levels in dentin and psychomotor development at 6 months of age. The relationship followed an inverse U-shaped association, with the strongest effect observed when comparing the highest tertile of Mn levels in teeth to the middle tertile of Mn levels in teeth (-3.6 points; 95% CI: -6.9, -0.2). Prenatal Mn levels in dentin were associated with mental and psychomotor development at 6 months only among children whose mothers were iron deficient during pregnancy. We did not observe a significant interaction with prenatal or postnatal blood lead concentrations in this cohort.

We assessed the association of Mn levels in teeth with cognition, attention, memory and motor functioning in the CHAMACOS children at age 7, 9 and 10.5 years. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects. We observed a significant increase of 0.7 and 0.9 points in NEPSY-II Memory for Designs immediate and delayed memory scaled scores (95% CI = 0.2–1.3, and 0.3–1.4, respectively) per twofold increase in postnatal dentine Mn concentrations. We also found an increase of 0.2 (95% CI = 0–0.3) in Dominant Hand Finger tapping scores with the dominant hand per twofold increase in postnatal dentine Mn concentrations. We did not observe any association between postnatal Mn exposure and WISC-IV scores at 7 years, but we observed a weak and positive linear association between postnatal dentine Mn and WISC-IV Perceptual Reasoning IQ and Working Memory IQ at 10.5 years (β for a twofold increase in concentrations = 2.6, 95% CI = 0.3–4.8; and β for a twofold increase in concentrations = 1.6, 95% CI = 0–3.2; respectively). We also observed positive associations between postnatal dentine Mn and WISC-IV Perceptual Reasoning IQ, Working Memory IQ, and Full Scale IQ in longitudinal models (β for a twofold increase in concentrations = 2.4, 95% CI = 0.3–4.5; β = 1.5, 95% CI = 0–3.0; and β = 1.8, 95% CI = 0.1–3.4, respectively).

Finally, in preliminary analyses of Mn hair concentrations we did not observe an association with 10.5 year IQ in models adjusted for child’s exact age, maternal education, poverty status and HOME score.

Specific Aim 3: To determine whether prenatal and childhood exposure to DDT/E, PBDEs and Mn are associated with timing of pubertal development in boys between age 9 and 13 years.

 

Pubertal assessments at 12 and 12.75 are not yet complete. However, we have conducted preliminary analyses of time to onset of puberty using interval censored survival analysis to evaluate the association of the onset of puberty in girls at 9 years of age and boys at 10.5 years of age with prenatal and childhood exposures to DDT/E, PBDEs and Mn.

DDT/E and PBDEs: We did not observe associations between prenatal or 9-year PBDE or DDT/E blood concentrations and onset of puberty in boys with the CHAM1 and 2 cohorts combined (Table 2). However, among boys from the original CHAM1 cohort (i.e., with more accurately measured prenatal serum concentrations), we found that prenatal DDT and DDE serum concentrations were associated with earlier onset of genital development (HR = 1.7; 95% CI = 1.1, 2.7 for each tenfold increase in DDE; HR = 1.5; 95% CI = 1.1, 2.1 for each tenfold increase in DDT). Concentrations of all prenatal PBDE congeners were associated with earlier onset of pubic hair development in CHAM1 boys (HR = 3.1, 95% CI = 1.3, 7.3 for each tenfold increase in ΣPBDEs) and BDE-153 also were associated with earlier genital development.

Mn: We had prenatal and postnatal measurements of Mn levels in tooth dentin for 219 participants for whom we also had Tanner staging information available at 9 years in girls and 10.5 years in boys. We observed an earlier onset of pubic hair development in girls that had higher prenatal Mn teeth levels, with a HR = 1.73 (1.12, 2.68) for every twofold increase in prenatal Mn tooth dentin.

Table 2.  Association of prenatal and 9-year-old lipid-adjusted PBDE and DDT/E concentrations (log10) with pubertal development in boys.

Specific Aim 4: To determine whether prenatal and childhood exposure to DDT/E, PBDEs and Mn are associated with hormone levels in boys at age 12

We collected early morning blood samples from 145 boys (113 CHAM1, 32 CHAM2), and laboratory analysis has been completed by Esoterix laboratory in Calabasas Hills, CA, for testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH). We conducted preliminary analyses of hormone levels in boys at age 12 and exposure to DDT/E, PBDEs and Mn in models adjusted for child’s exact age and body mass index (BMI) at the 12-year visit. We did not observe a relationship with measured prenatal concentrations of DDT/E and any hormone measurement. For measured prenatal concentrations of PBDEs, we found significant associations between levels of BDE-153 and LH and testosterone. A tenfold increase of BDE-153 concentration in prenatal blood resulted in a 160 percent increase in LH (p = 0.003) and a 200 percent increase in testosterone (p = 0.01). Results were similar and remained significant using back-extrapolated BDE-153 concentrations in CHAM2 participants. There were no associations between DDT/E or PBDEs measured in children at 9 years of age and hormone levels in boys at age 12. Prenatal Mn levels measured in tooth dentin were not related to hormone levels in boys. However, a twofold increase in postnatal Mn dentin levels was associated with a 15 percent increase in FSH (p = 0.04). In future analyses, we will include Tanner stage at the 12-year assessment in the models and will explore nonlinear relationships using generalized additive models.

Other Studies

  • OPs Pooling Project
  • DAPs and Respiratory
  • Sulfur and Respiratory
  • BPA and Behavior/Obesity

 

Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

Specific Aim 1: To measure Mn, PBDEs and DDT/E in shed deciduous teeth (Population: CHAMACOS children participating since birth)

Mn: We have successfully developed a method for measuring Mn in human teeth by laser ablation ICP-mass spectrometry (LA/ICP/MS), including analysis of 307 teeth collected from the CHAMACOS cohort. Rather than calculate one estimate of cumulative exposure over the entire prenatal period, we have used a method to distinguish Mn exposure experienced in the 2nd trimester from that experienced in the 3rd trimester. We observed a significant association (rspearman = 0.36, p = 0.001, n = 77) between Mn levels in the entire prenatally formed dentine [as 55Mn:43Ca area under the curve (AUC)] with floor dust Mn loading (μg Mn/m2 floor area) and a stronger relationship with Mn levels in dentine formed only in the 2nd trimester (rspearman = 0.40; p = 0.0005; n = 72), likely because dust samples were collected in the 2nd trimester. We also have compared Mn levels in cord blood and mantle dentine. While there was no significant association of 55Mn:43Ca AUC of all prenatal sampling points with cord blood Mn (rspearman = -0.01; p = 0.99), 55Mn:43Ca in the sampling point immediately adjacent to the neonatal line in each tooth showed a significant positive correlation with cord blood Mn (rspearman = 0.70; p = 0.003; n = 16). These findings were published in Environmental Science & Technology (Arora, et al., 2012).

PBDEs and DDT/E: Dr. Andreas Sjodin at the Centers for Disease Control and Prevention (CDC) in Atlanta attempted to measure PBDEs and DDT in anonymous deciduous teeth collected from patients demographically similar to the CHAMACOS cohort. Using whole tooth digestion, neither PBDEs nor DDT were detected. Additional anonymous deciduous teeth were obtained from a local clinic. Dr. Arora has extracted the dentin from another set of teeth to determine if more sensitive analyses to measure organochlorine (OC) compounds (i.e., DDT) or PBDEs are feasible.

Specific Aim 2: To determine the relationship between Mn, PBDE and DDT/E levels in teeth with other relevant biological measures

Laboratory measurements of Mn have been completed for 330 biological samples, including 202 whole blood samples (maternal blood, cord blood, child’s blood) and 128 urine samples (maternal at 26 weeks gestation and child at 24 months) by Dr. Smith at the University of California, Santa Cruz (UCSC). We analyzed Mn in pre- and postnatal dentin and enamel in deciduous teeth from 62 children using laser ablation ICP-mass spectrometry. We also measured Mn concentrations in maternal, cord and child blood, and maternal and child urine and examined the interrelationships of Mn levels in all matrices.

Mn levels (Mn:Ca ratio) were higher in prenatal than postnatal dentin (geometric mean [GM] = 0.51 vs. 0.16, p < 0.0001). Maternal blood Mn concentrations increased from 26 weeks gestation to delivery (GM = 14.6 to 20.7 μg/L, p = 0.001) and child blood Mn concentrations decreased from cord blood to 24 month blood samples (39.9 vs. 25.0 μg/L, p = 0.005). Mn levels in tooth dentin during the 3rd trimester were positively correlated with Mn concentrations in cord blood (rs = 0.31) while there was a negative correlation between prenatal Mn levels in enamel and Mn concentrations in maternal blood at 26 weeks gestation (rs = -0.36). We did not find any significant differences in Mn urine concentrations over time and did not observe significant correlations between Mn levels in teeth and urine, suggesting that urinary concentrations are not a useful measure of environmental Mn exposure. 

We observed significantly higher (p < 0.05) levels of Mn in prenatal dentin, prenatal maternal blood and 24-month urine from children if there was a farmworker living in the home during the corresponding time period compared to no farmworker living in the home. Prenatal Mn levels in dentin and cord blood also were correlated with Mn loading in prenatal house dust samples (rs = 0.27 and 0.29, respectively; p < 0.1). Tooth dentin and blood Mn concentrations had the strongest associations with potential sources of Mn exposure in the home.

Specific Aim 3: To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth, hair and child blood.

Mn in dust: We collected house dust samples from 378 residences enrolled in the CHAMACOS study with a second sample collected approximately 9 months later from 90 of the residences. House dust samples were analyzed for Mn using ICP optical emission spectroscopy. Information from interviews, home inspections and pesticide use reports was used to identify potential predictors of Mn dust concentrations and loadings. Mn was detectable in all dust samples. The median Mn concentration was 171 μg/g and median Mn loading was 1,910 μg/m2 at first visit. In multivariable models, Mn dust concentrations and loadings increased with the number of farmworkers in the home and the amount of agricultural Mn fungicides applied within 3 kilometers of the residence during the month prior to dust sample collection (Figure 2). Dust concentrations of Mn and other metals (lead, cadmium and chromium) were higher in residences located in the southern Salinas Valley compared to those located in other areas of the Salinas Valley. Dust loadings of Mn and other metals also were higher in residences located on Antioch Loam soil than other soil types, and in homes with poor or average housekeeping practices. Agricultural use of Mn containing fungicides was associated with Mn dust concentrations and loadings in nearby residences and farmworker homes. Housekeeping practices and soil type at residence also were important factors related to dust metal concentrations and loadings. A manuscript was submitted to Science of the Total Environment and we have responded to comments from reviewers.

Mn in teeth: Participants in our analysis included 207 children enrolled in the CHAMACOS study. Mn was measured in teeth using LA-ICP-mass spectrometry. Our purpose was to determine environmental and lifestyle factors related to prenatal Mn levels in shed teeth. We found that storage of farmworkers’ shoes in the home, maternal farm work, agricultural use of Mn-containing fungicides within 3 km of the residence, residence built on Antioch Loam soil, and Mn dust loading (μg/m2 of floor area) during pregnancy were associated with higher Mn levels in prenatal dentin (p < 0.05). Maternal smoking during pregnancy was inversely related to Mn levels in prenatal dentin (p < 0.01). Multivariable regression models explained 22–29 percent of the variability of Mn in prenatal dentin (Table 3). Our results suggest that Mn measured in prenatal dentin provides retrospective and time specific levels of fetal exposure resulting from environmental and occupational sources.

Table 3. Percent change of Mn in prenatala dentine and partial coefficient of determination (r2) for prenatal predictor variables in multivariable models for tooth Mn (n = 206) and the subset with tooth and dust Mn (n = 130).

Mn in hair: In anticipation of using hair Mn levels as an exposure biomarker and the absence of a validated methodology for the accurate determination of hair Mn without external contamination, we developed and fully validated a methodology for the cleaning and analysis of hair Mn, showing in the process that prior published studies of hair Mn are likely erroneous (Eastmann, et al., 2013). We have collected hair samples from 455 children (145 boys and 310 girls). Dr. Smith at UCSC has analyzed samples from 136 participants. Preliminary analyses indicate that hair Mn concentrations were not related to baseline maternal demographics or the use of hair care products prior to sample collection. In preliminary analyses, we did not observe an association between hair Mn concentrations and 10.5 year IQ in models adjusted for child’s exact age, maternal education, poverty status and HOME score.

Specific Aim 4: To identify population correlates of PBDEs and DDT/E exposure in 9-year-old boys

CDC has analyzed 308 CHAMACOS blood samples for PBDEs and DDT/E in mothers and children from the 9-year visit. Dr. Andreas Sjodin will be lead author on the manuscript examining population correlates of PBDE and DDT/E exposures in 9-year-olds.

Back-extrapolation of DDT/E and PBDEs: We evaluated three back-calculation modeling approaches (PBPK, deletion substitution algorithms and SuperLearner) in study population subsets where serum levels were measured in mothers at 26 weeks of pregnancy and 9 years after delivery in mothers (n = 94), children (n = 161), or both mothers and children (n = 89). Model performance was assessed using the root mean squared error (RMSE) and coefficient of determination (R2) of log10-transformed back-extrapolated versus measured levels. For all compounds and subsets, SuperLearner outperformed the other approaches with RMSEs and R2s ranging from 0.10–0.31 log10 ng/g and 0.58–0.97, respectively. Typically, model RMSEs were lower and R2s were higher for p,p’-DDT/E than PBDE congeners, and estimations using maternal levels were more accurate compared to child levels. The pharmacokinetic model performed well when back-extrapolating prenatal levels from maternal levels for compounds with longer half-lives such as p,p’-DDE and BDE-153 (RMSEs = 0.21 and 0.28 log10 ng/g and R2s = 0.88 and 0.57, respectively). Results demonstrate the ability to accurately back-extrapolate prenatal levels from maternal levels 9 years after delivery, with SuperLearner performing the best based on our fit criteria.

Other Studies

  • DAPs in child urine: A manuscript examining changes in pesticide excretion during organic food intake has been submitted.
  • BPA: An article on determinants of BPA exposure in pregnant women was accepted by Environment International (Quiros-Alcala, et al., 2014).
  • Within and between subject variability: Dr. Bradman, et al., published a paper in Environmental Health Perspectives examining within and between subject variability in organophosphate metabolite excretion in young children.
  • Environmental quality in child care: Dr. Bradman published two studies examining environmental quality in child care, one focusing on flame retardants and one on phthalates.
  • Organophosphate levels and PON1 in blood: Dr. Karen Huen (former graduate student with us) published a study reporting on chlorpyrifos and diazinon levels in maternal and infant blood and PON1 status.
  • Dietary transitions in a Neanderthal infant: Dr. Manish Arora with Drs. Eskenazi and Bradman and other scientists, published a paper in Nature showing breast feeding transitions in a Neanderthal infant. The study used teeth and data from the CHAMACOS cohort to validate the method applied to a fossil Neanderthal tooth.

Project C: Epigenetics Project: Epigenetic Effects of DDT/E and PBDEs on Puberty

Specific Aim 1: To analyze global DNA methylation in newborn children by three different assays

Pyrosequencing assays were used to measure methylation of Alu and LINE-1 repetitive elements in newborns and 9-year-old children. We found significant associations of DNA methylation with host factors. Levels of DNA methylation were lower in 9-year olds compared to newborns and were higher in boys compared to girls (Figure 3). These findings were recently published in Environmental and Molecular Mutagenesis (Huen, et al., 2014). Additionally, we observed no correlation between LINE-1 and Alu methylation levels at either age suggesting that the two assays represent different portions of the methylome.

Figure 3. Effects of sex and age on LINE-1 and Alu DNA methylation (n = 246 cords and 246 9-year-olds).

 

The 450K assay was performed in blood samples of 250 newborns and 250 9-year-olds from the CHAMACOS cohort. Our newly developed All Sample Mean Normalization (ASMN) procedure for normalization of methylation data performed consistently better than alternative methodologies at reducing batch effects and increasing repeatability among technical replicates. ASMN was submitted as open source Bioconductor software package in December 2013 and described in our recent publication in Epigenetics (Yousefi, et al., 2013).

Specific Aim 2: To determine ontogenetic changes in global DNA methylation in blood of children between birth and 12 years

To determine the longitudinal changes in repetitive element DNA methylation (Alu and LINE-1), pyrosequencing assays were performed in > 600 blood samples collected from CHAMACOS children at multiple time points from birth through early adolescence. LINE-1 global DNA methylation was found to decrease 0.3 percent per month increase in child age (95% CI: 0.2–0.6%). A similar decreasing trend was found for Alu methylation, but this association was not statistically significant (p = 0.18). These data were recently published in Environmental and Molecular Mutagenesis (Huen, et al., 2014). Analysis of the results of genome-wide methylation by the 450K Beadchip are currently in progress.

Specific Aim 3: To investigate the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global DNA methylation

We observed a consistent trend of lower Alu methylation in fetal blood with higher prenatal DDT/E exposure, particularly after adjusting for cell type composition (Figure 4). Furthermore, associations of prenatal exposure with levels of LINE-1 methylation were only identified after examining the coexposure of DDT/E with PBDEs simultaneously. Our data suggest prenatal exposure to POPs may be linked to hypomethylation in fetal blood and that accounting for coexposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies.

 

Figure 4. Alu methylation and prenatal o,p’-DDT exposure in newborns (n = 94) after adjusting for sex and cell type composition. Higher prenatal exposure to o,p’-DDT was associated with lower levels of methylation (p = 0.02, b(95%CI): 20.37(20.69, 20.05)).

Specific Aim 4: To determine whether global methylation is associated with onset of puberty and hormonal changes

In girls there was a suggestive trend of accelerated breast development (Tanner Stage > 1) at age 9 with increased cord LINE-1 methylation (OR(95% CI): 1.23(0.88,1.73)). Furthermore, this relationship was somewhat stronger at age 10.5 (OR(95%CI): 1.76(0.87,3.59). Similarly, odds of pubic hair development at age 9 were positively associated with increased 9-year LINE-1 methylation (OR(95%CI): 1.18(0.84,1.67)) and this relationship was even stronger at age 10.5 (OR(95%CI): 1.3(0.95,1.8)).

Hormone levels in 12-year-old CHAMACOS boys (n = 112) were comparable to reference levels for children of this age group. Repeat element methylation was significantly associated with differences on hormone levels in boys. For instance, a one-unit increase in Alu methylation (cord blood) was associated with an 80 percent increase in testosterone levels (p = 0.02; Figure 5). Additionally, both Alu and LINE-1 methylation (9 years) were inversely associated with LH at age 12 (p = 0.05 and 0.02, respectively).

Figure 5. Cord blood Alu Methylation and Testosterone at age 12.

Specific Aim 5: To examine site-specific methylation in relation to age, sex, exposure to DDT/E and PBDEs and puberty onset

We assessed the association of prenatal DDT/E exposures on DNA methylation measured by 450K Beadchip assay in cords (n = 308) and 9-year-old children (n = 213) but did not find any associations after adjusting for multiple comparisons (using false discovery rate (FDR)).

For prenatal PBDE exposures, we identified eight significantly associated CpG sites (three were significant after Bonferonni correction and eight by FDR), several of which were consistently associated across different BDE-congeners, in CHAMACOS fetal blood DNA (Figure 6). We did not find any significant association in 9-year-old blood DNA. We are currently preparing a manuscript on these results (and those with DDT/E exposure).

 

Figure 6. Manhattan plot for association between prenatal log BDE-100 and 450K methylation at birth (red line Bonferonni cutoff for multiple testing, significant hits by FDR in blue rectangle).

We did not find significant association of site-specific methylation (cord blood and 9 years) with puberty status (Tanner Stage > 1) at age 10.5 in girls or boys. However, methylation at age 9 was significantly associated with testosterone levels in 12-year-old boys for five different CpG sites after adjusting for multiple testing by FDR. These CpG sites were located in the following genes: NBAS, MIR574, TTC40, FBRSL1, and THEG. Using structurally enhanced pathway enrichment analysis (SEPEA) of this methylation data, we found that several important pathways were significantly enriched, including glutathione metabolism, amino sugar and nucleotide sugar metabolism, and the PPAR and insulin signaling pathways.

Biorepository Core

Blood Specimens: We continued to expand our blood collection from the original CHAMACOS birth cohort (CHAM1) and the second cohort of newly enrolled at 9 years children and their mothers (CHAM2). We have collected blood from 564 children and 585 mothers. We completed fasting blood collection at 12 years from 181 CHAMACOS boys. In April 2014, we developed and piloted a complicated new protocol for the 14-year-old visit that, in addition to the Center grant, is supported by two recently funded R01s (PIs Holland and Deardorff). Assessment of 600 CHAMACOS participants from both subcohorts (CHAM1 and CHAM2) was successfully launched in May 2014.

Samples are shipped from the CHAMACOS Field Office in Salinas to the SPH Biorepository at the University of California, Berkeley (UC Berkeley) and processed according to SPH Biorepository Standard Operating Procedures. Banked specimens include multiple aliquots of serum, plasma, clots, buffy coats, whole blood, red blood cells and blood smears.

Saliva: In addition to blood collection, we have developed a new saliva collection protocol for CHAMACOS children with the target collection at 14 years of age and have completed an initial pilot collection of saliva by two methods (Oragene for DNA stabilization and repeated sampling for cortisol assessment). Saliva is initially processed in the field office and banked at -80°C until shipment to the CERCH Biorepository at UC Berkeley, where it will be stored for future analyses.

RNA: Within the past year, we have piloted RNA isolation from different fractions of stabilized blood samples in order to assess gene expression in CHAMACOS children. The pilot dataset was assessed by qPCR and by NanoString. This expression data will be used to validate DNA methylation data generated for CHAMACOS children as a part of the Epigenetics Project (Project C). Multiple genes assessed in the study were selected based on their roles in metabolism and obesity, and thus also can be used to investigate important research questions regarding the relationships between environmental exposures, epigenetics, gene expression, and adverse health outcomes such as child obesity for the renewal of the Center grant.

Deciduous teeth: Additional samples were shipped to Dr. Manish Arora, now at the Icahn School of Medicine at Mount Sinai, for analysis of Mn, and we continued to collect teeth from CHAMACOS children and store them in the SPH Biorepository for future analyses. Additionally, measurements of barium in CHAMACOS teeth provided validation for studies by Dr. Arora examining breastfeeding habits in a Neanderthal infant. A paper on this study was published in Nature.

Urine specimens: We shipped 341 prenatal urine samples from the CHAMACOS mothers to Dr. Stapleton at Duke University for the analysis of urinary metabolites of organophosphate flame retardants (R21, Dr. Asa Bradman PI). More than 900 maternal urine samples were shipped to the CDC (Dr. Calafat) for phthalate analysis.

Dust samples: We shipped 125 dust samples from the prenatal CHAMACOS visit to Dr. Heather Stapleton at Duke University for analysis of organophosphate flame retardants.

Other Samples: All biological and environmental samples collected and banked by the CHAMACOS project starting in 1998 through 2013 (more than 150,000) have been used extensively for analysis of multiple biomarkers of pollutants and their association with health outcomes. Since 2003, more than 65 peer-reviewed research publications, 12 reviews and book chapters, 10 Ph.D. dissertations and more than 30 student projects have been conducted using this sample collection. The number of presentations and posters exceeds 200.

Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE) samples: Our Biorepository Core assisted with the recent launch of the VHEMBE study in Limpopo, South Africa (R01, Dr. Brenda Eskenazi PI). We helped to develop collection and processing protocols for 750 pregnant women who will be enrolled in the study and their children. Thus far, two large shipments of samples from the VHEMBE study have been received at the SPH Biorepository for long-term biobanking. Samples include breast milk, urine and maternal and umbilical cord blood divided into serum, plasma, whole blood, clot, buffy coat and red blood cells.

Biorepository expansion: Supplemental EPA funding allowed us to purchase three new freezers (-80°C) to replace existing freezers that have exceeded their lifetime, increasing our total number of deep freezers to 26. The new addition of freezers to our Biorepository is essential to allow us to maintain adequate storage space for the thousands of samples added to our sample bank each year.

Biorepository database: We continue to maintain a sophisticated SQL database that allows us to uniquely barcode and track the hundreds of thousands of samples collected over the course of the CHAMACOS project. User interface features are upgraded as necessary in order to continue efficient management of our data and sample information. All data are regularly backed up, and a replica SQL server is stored off site with all the software to reestablish the Biorepository functions in case of any disaster. We also maintain a designated backup generator to protect all the freezers and other essential equipment.

Community Outreach and Translation Core

Specific Aim 1: To disseminate Center research findings to study participants, the Salinas Valley community and other stakeholders

Newsletter: In November, we disseminated the 2013 CHAMACOS newsletter, La Semilla, for participants 2 weeks before the annual Participant Community Forum. The newsletter is in Spanish and English and provides a means for parents and children to discuss the newsletter content. (Parents mostly speak Spanish and children who mostly speak English.) The newsletter is available on our website (http://cerch.org/wp-content/uploads/La-Semilla_2013_12.01.13-1-8.pdf).

This issue of La Semilla featured a letter from Center Director Dr. Eskenazi, information on recent research findings, word games for children, and an announcement about upcoming participant forums. The research findings highlighted included three papers that were to be published soon: our organic diet intervention study, studies linking pesticides to asthma symptoms, and exposure pathways of manganese. Newsletter content is written to be accessible to low-literacy readers. Each article summarized the study conclusions and the relevance of the study to residents of the Salinas Valley. Since each of the three studies was related to pesticides, we also presented simple information on methods to reduce pesticide exposure: (1) washing fruits and vegetables prior to eating them, (2) washing their hands regularly, and (3) changing out of farm work clothes and shoes before entering their home.

The final section of the newsletter—word games to engage children—included a crossword puzzle and a word scramble, both of which used words found throughout the newsletter. In order to complete the puzzle, one would have to read through the content of the newsletter. As an incentive, a prize was provided to children who brought a completed crossword puzzle and word scramble to the forums. Several children brought the completed versions of the crossword puzzle to the community forums.

The La Semilla newsletter also included an announcement for the annual CHAMACOS community forums, including information about receiving individual study results. We also included an example of our returning results forms with a detailed explanation of each element in the report. This announcement was the first part of a comprehensive plan to notify participants about their access to study results, which we returned during the community forum.

Participant Community Forum: At the end of each year, we hold an event for CHAMACOS participants to build community and share the latest research findings. The event provides an opportunity to show our appreciation to participants for their involvement and to give an update on study findings in a manner that is engaging, informative and useful. In past years, we have held one forum in Salinas due to resource restrictions. This year, through effective planning, we added a second forum in the city of Greenfield, which provided an opportunity to reach participants who live in the Southern part of Monterey County. At both forums we provided food, a raffle, a presentation for adults on research findings, and activities for children. The first forum took place on Saturday, December 7, 2014, in Greenfield was attended by 117 adults and 110 children. The Salinas forum took place a week later and was attended by 136 adults and 77 children.

This year, we also returned individual-level results to participant mothers who wanted to know their and their children’s results for chemical measurements. At the presentation, we made it clear to participant mothers that receiving these reports was completely voluntary. Participant mothers who chose to learn their results received a packet that included their and their children’s levels of DDT/DDE, PBDEs, PCBs and BPA in comparison with all CHAMACOS participants and a sample from NHANES and background information on each chemical. To ensure that participants understood the information in their packets, we trained a group of 20 CHAMACOS staff to become “Returning Results” counselors. At the forum, each participant mother had the chance to sit down with a counselor to go through the report that she received. Senior scientific investigators also were available to answer questions. Participating mothers asked questions about how to understand their chemical level results, what the results meant, and how to prevent exposure to these chemicals. Participating mothers had the option of having their children or other family members sit with them as they learned about chemical levels. Forty-two participant mothers at the Greenfield forum and 47 at the Salinas forum requested individual-level results.

A major contributor to the success of these forums was the support provided by CHAMACOS staff and members of the CHAMACOS Youth Community Council (YCC). Staff and YCC members helped with several tasks at the event, including registering participants, serving food, presenting information, providing “Chemical Levels” counseling, translating, leading activities and running the raffle. We had 20 CHAMACOS staff and students from Berkeley, 7 CHAMACOS staff from Salinas, and 12 Youth Community Council members participate in the two forums.

Youth Community Forum: This year, we conducted two Youth Community Forums (YCFs) for participant children of the CHAMACOS study. The first YCF was held at the two community forums; 65 children participated at the Salinas forum and 35 children participated in the Greenfield forum. The activities were led by Daniel Madrigal, CHAMACOS Community Outreach Coordinator, and members of the CHAMACOS Youth Community Council. The YCFs started with an icebreaker to create a comfortable social environment amongst participating children. Two subsequent activities were conducted in small groups of 5–10 children; each of these small groups was led by a YCC member. The first of the environmental health–themed activities was a “trivia game” where each small group of children would use the current issue of La Semilla to answer questions related to environmental health. This activity encouraged children to discuss the content and findings from the La Semilla newsletter. The second activity was a modified game of Pictionary, where one child would draw a word related to environmental health and act it out, while the rest of the group tried to guess the word. Children were very engaged during the ice breaker and the small group activities, with both of the latter activities proving entertaining methods to introduce basic environmental health themes.

The second YCF was a field trip to California State University Monterey Bay (CSUMB) on May 5, 2014. The purpose of the trip was to expose CHAMACOS children to science and educational opportunities available at a local university. The CHAMACOS children are entering high school, and this is a critical time where they begin to make choices about their life trajectory. In order to be accepted into a college or university, they need to begin to dedicate a significant effort to their academic performance and extracurricular activities starting at the beginning of high school.

We hired a charter bus to drive 25 CHAMACOS participant children from the Salinas Valley to CSUMB. At CSUMB, CHAMACOS children participated in several activities to learn about college life and scientific research. The activities were facilitated and designed by two undergraduate students who are members of the CSUMB Under Represented Opportunities Program. In addition to leading the activities, these two students shared the paths they took and barriers they had to overcome before arriving at CSUMB. Activities at CSUMB included a tour of the library, sitting in on a lecture for the class “Introduction to Biology,” visits to scientific labs, lunch in a campus cafeteria, and a scavenger hunt of points of interest on campus. The field trip’s activities were intended to introduce the university to the children, inform them about interesting opportunities in the sciences, and encourage them to work hard to take the steps needed to gain acceptance into a university like CSUMB.

Electronic Newsletter: We sent out two e-newsletters in 2013 to more than 900 subscribers. The first informed subscribers about a study published in Environmental Health Perspectives on the fumigant methyl bromide and birth outcomes. This publication received attention from local news media, and we created a simple factsheet to help community members and other stakeholders understand the methods and findings from the study. Following the paper’s publication of the study, a critique of the study was produced by the consultant group Exponent. We included both the critique and our response in the e-newsletter. We also used this issue of the newsletter to invite subscribers to follow our new Facebook page (www.facebook.com/cerchberkeley).

The second e-newsletter was sent out before the winter holidays to publicly share our appreciation of the many research participants and collaborators who are essential to the success of our projects. 

Dissemination to larger community and targeted groups: We continued our efforts to share Center research findings with the Salinas Valley community through targeted meetings with community groups and key stakeholders, participation in community events, and media interviews about our work. Nearly 58 meetings with a wide range of groups were conducted, most of them in the Salinas Valley, to discuss recent Center findings and other environmental health issues. Center staff also participated in several local health-related events, such as health fairs and town hall meetings, to discuss the Center’s research. Through these efforts we made contact with 702 men, 1,372 women and 903 children from May 1, 2013, to February 28, 2014. In November 2013, we presented the latest scientific findings to our Community Advisory Board, which includes representatives from the health, agriculture and farmworker communities.

Dissemination to the scientific community: A list of pertinent scientific publications is included with the progress report, along with a list of presentations at professional and scientific meetings. We also have presented our findings at other local meetings and universities.

Science Day: On February 26, we conducted a webinar presentation on recent study findings to CHAMACOS study staff. Staff members from the Berkeley office, Salinas office and laboratory were in attendance. At this meeting, we solicited feedback from staff on the future direction of the study.

Website: On our website, www.cerch.org, we have developed an online resource center where specific audience groups can access information on environmental health hazards and how they can protect themselves. These audiences include adults, families, parents of young children, teens, community groups and health professionals. As new resources are developed by our Center, they are posted to the ORC to facilitate rapid dissemination to these audience groups. In 2013, www.cerch.org had 17,642 unduplicated visitors. To expand our online outreach efforts, we also started a CERCH Facebook page where interested individuals can learn about breaking news related to the Center. The CERCH Facebook page is available at www.facebook.com/cerchberkeley.

Specific Aim 2. To increase awareness about children’s environmental health among low-income Latino communities, clinicians, and service providers through widespread dissemination of innovative outreach and educational programs

Outreach to pregnant women: This year, we developed a “How-to” Guide for providers as part of the Prenatal Environmental Health Kiosk for providers. The guide is a one-page document that explains the benefits of the Prenatal Kiosk, and how to access this resource from our website. The “How-to” Guide is available on our website at http://cerch.org/wp-content/uploads/Kiosk-Flyer-3.5.13.pdf.

To disseminate the Prenatal Kiosk throughout California, we packaged the Prenatal Kiosk into an easy-to-use bundle. The bundle contains software for the PC version of the Kiosk, the Mac version of the Kiosk, the pdfs for the “How-to” Guide, and pdfs for the colorful and popular Kiosk tri-fold brochures on asthma, air pollution, pesticides, carbon monoxide and sun exposure. The bundle was sent out to 60 coordinators of the Comprehensive Perinatal Services Program from each local health jurisdiction in California. This program provides prenatal services to pregnant women in each local health jurisdiction throughout California. Several coordinators responded that they were interested in using the resource.

Outreach to child care providers: We continue to provide environmental quality in childcare settings in the Salinas Valley. We have also expanded our reach by developing new resources and delivering trainings throughout California. We have been contracted to provide two sets of trainings to childcare workers and school staff, including nurses and administrators in Imperial Valley, CA (March 2013), and Fresno, CA (March 2014). These trainings were conducted with the Pediatric Environmental Health Specialty Unit at the University of California, San Francisco (UCSF) and were funded by EPA Region 9.We have also developed a new resource for childcare providers to bring attention to hazardous cleaning products and provide accessible alternatives. The Green Cleaning Toolkit includes posters, handouts, factsheets and a PowerPoint presentation to help child care providers maintain a toxic-free environment. These resources include information on cleaning products to avoid and safe alternatives. The toolkit was disseminated at eight trainings throughout the San Francisco Bay Area. The toolkit has also been shared with regional and national organizations that have an interest in maintaining healthy environments in schools and childcare settings. The Green Cleaning Toolkit is available online at www.cerch.org/greencleaningtoolkit.

Recently, we have also been approved to develop an Integrated Pest Management course for pest control companies serving childcare centers by the California Department of Pesticide Regulation. The first pilot of this course was presented on May 21, 2014.

Outreach to social service organizations: Center staff continue to provide presentations to community groups in Monterey County on the following topics: Preventing Pesticide Exposure, CHAMACOS Findings Overview, Healthy Homes, Heat Illness Prevention, and Environmental Quality in Early Childcare Environments. Through these trainings and presentations, we have reached 2,977 individuals in the Salinas Valley.

Outreach to farmworkers: We continue to maintain the Farmworker Council and met with this group in November 2013 to discuss outreach strategies and facilitate farmworker input into Center research and health promotion activities. We send the Farmworker Council Spanish translations of our research summaries, just as we share these summaries with the Community Advisory Board. Additionally, many of the participants of our other presentations and in the Salinas Valley are farmworkers.

Outreach to growers and the agricultural industry: We continue to have a good working relationship with our Agricultural Council, sharing study summaries and abstracts before research articles are released. We also have made ourselves available to talk in person or by phone with Agricultural Council members if they have questions related to new publications. We held an in-person meeting with members of the Agricultural Council in February 2014 to share and discuss the latest findings from our study.

Specific Aim 3: To build the capacity of Salinas Valley youth to promote healthy environmental policies in their community

We have maintained and expanded the CHAMACOS YCC, whose goal it is to build youth capacity to promote healthy environmental policies in Salinas. The YCC now consists of 15 youth from Salinas, CA, and we continue to meet with them twice per month for 2.5-hour sessions. The youth now are working on two main projects: (1) sharing the findings and recommendations from their study of the walking environment in Salinas and (2) completing the HERMOSA study, a project where youth have taken a lead in investigating endocrine disrupting chemicals found in personal care products used by adolescent Latinas.

For the walkability project, the YCC created a report based on a community walkability survey they conducted with 271 adult and child residents from the city of Salinas. The report describes major findings from the survey along with recommendations on how to make Salinas a more walkable city. The report can be accessed at http://cerch.org/wp-content/uploads/YCC-Walkability-Report-English-FINAL.pdf. On March 28, four leaders from the YCC presented the report to local county supervisor Jane Parker, explaining the survey, the findings and recommendations. The report was presented to this supervisor because she had been involved in the previous survey of walkability report that had taken place in 2004. The youth facilitated the meeting themselves and gained confidence by presenting a well-prepared presentation for a community leader. Supervisor Parker thanked the youth for their work and provided several suggestions on actions the YCC could take to enact their recommendations. One recommendation was to bring attention to a smartphone application that allows local residents to easily report blight in the city.

The HERMOSA study, funded by the California Breast Cancer Research Program, is a community-based multiyear project examining endocrine disruptor chemical exposures from personal care products to Latina teenagers. This project builds on previous efforts of the YCC. In the summer of 2013 we completed the intervention phase of the HERMOSA study, which was to test the effectiveness of using low-chemical personal care products over a 3-day period to reduce exposure to common endocrine disruptors. In February 2014 we received laboratory results from the study and began to analyze the data with the youth. We have also started to prepare manuscripts with leaders from the YCC to publish studying findings from the HERMOSA study.

On March 17, 2014, we brought YCC members on a field trip to the California Department of Public Health laboratory where the HERMOSA study samples were analyzed for endocrine disruptors. Scientists from the lab gave presentations on mass spectrometry, the California Bio-monitoring Program, and environmental regulation in California. The YCC also had the chance to see the lab machines that processed samples for the HERMOSA study. YCC members also visited the CERCH Berkeley office and had the chance to meet with a former YCC member who now is an undergraduate in public health at UC Berkeley and an assistant with CERCH.

In May and June, we focused the efforts of the YCC on the HERMOSA study’s educational component. The YCC created educational materials for Latina teens to teach them how to avoid personal care products with endocrine disrupting chemicals. These materials are available at community events and at the HERMOSA study webpage (www.cerch.org/hermosastudy). The YCC is currently involved in planning a community forum for HERMOSA participants, where YCC members will lead a presentation, conduct workshop activities, and return individual results to participants.

In addition to the work on the walkability report and the HERMOSA study, the YCC is also contracted by the local health department in Monterey County to teach participatory research techniques to youth in the neighboring community of Seaside, CA. YCC members trained Seaside youth on how to conduct a Photovoice project, how to conduct a community-based survey, and how to present participatory research findings in a community setting.

YCC professional staff members have written, and continue to write, letters of recommendation to promising program members as they apply to colleges and universities, including those in the University of California (UC) and California State University system. Four current members of the YCC have been accepted to schools in the UC system and plan on attending these schools in the upcoming Fall 2014 semester.

Specific Aim 4: To educate policy makers at the local, state and national levels about Center research findings and children’s environmental health priorities

CHAMACOS research has been shared with policy makers at several levels of government. At the local level, the YCC presented their findings of the Walkability Report to staff at the local health department and Monterey County Supervisor Jane Parker.

On the regional level, Jose Camacho met with a team of officials from the EPA to talk about the success of the Train-the-Trainer program our Community Outreach Program completed in 2012–2013. Region 9 Administrator Jared Blumenthal attended this meeting.

Our research was shared at the national level when we gave comments to the proposed changes to the Worker Protection Standard (WPS). The WPS was introduced in 1992 and was designed to protect farmworkers from pesticides. New changes in the WPS have been proposed to make the regulation more effective. We submitted comments to EPA that included CHAMACOS research findings. Insights from exposure and health outcome studies by CHAMACOS can help EPA staff develop regulations that will prevent exposure to pesticides and protect the health of farmworkers and their families.

Project-Generated Resources: We continue to maintain and add new resources to our online resource center at www.cerch.org. The website contains general information on various CERCH studies, including CHAMACOS, as as well as pages tailored to distinct audience groups.

Prenatal Kiosk “How-to” Guide (PDF) Exit — A resource for practitioners who work with pregnant women and are interested in sharing the Prenatal Environmental Health Kiosk. The “How-to” Guide is available on our website.

Methyl Bromide Birth Outcomes Factsheet Exit —This resource was developed to help lay members of the public easily understand the science and the findings that appeared in a publication that received substantial attention in the news media. The factsheet is available online.

CHAMACOS, 15 Years in the Fields Video Exit —This video was presented at the Center's meeting in November. The video is available for viewing on our website.

CHAMACOS YCC, Community Walkability Survey (PDF) Exit —An overview of methods, results and recommendations based on the survey completed by the YCC in 2013. The survey is available online at .

Future Activities:

Project A: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty

In the next year, we will complete as many 12.75 visits as we are able before funding expires. We will complete data entry and cleaning of the 12-year questionnaire and neurodevelopment data, as well as for ages 12 and 12.75 Tanner data. Statistical analyses of prenatal PBDEs and DDT/E exposure in CHAM2 study participants (Aims 2 and 3) will begin now that back-extrapolated levels for CHAM2 are available.

Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

In the next year, we will complete analyses of correlates of PBDE and DDT/E exposure. We expect to publish at least three manuscripts this year, one examining the interrelationships of Mn in biological samples (in review by co-authors), one on the best method to back-estimate maternal PBDE and DDT/E levels in adult women (near completion), and another on correlates of PBDEs and DDT/E in 9-year old boys. Future analyses also will utilize hierarchical models to evaluate the relationship between predictors of exposure and prenatal and postnatal Mn levels in deciduous teeth.

Project C: Epigenetics Project: Epigenetic Effects of DDT/E and PBDEs on Puberty

In the next year, we plan to finalize the analyses of complex multidimensional data from 450K Beadchips and to focus on validation of the found “hits” by assessment of expression of these genes by Nanostring and qPCR, as well as by alternative platform such as targeted bisulfite pyrosequencing or next-generation sequencing. Several manuscripts currently in preparation will be submitted for publication.

Biorepository Core

The Biorepository Core will continue to assure that all environmental and biological specimens are collected, managed and stored so as to maximize their future utility..

Community Outreach and Translation Core (COTC)

All of the primary activities described above will continue in the next year. We will continue active engagement with our Youth Community Council, including ongoing activities as part of the HERMOSA study. We will continue targeted outreach to community groups and respond to invitations for presentations. Targeted outreach will focus on farmworkers, teachers and childcare providers. We will maintain ongoing contact with our Community Advisory Board and Agriculture and Farmworker Councils and will have in-person meetings during the fall of 2014. We also will continue dissemination to the scientific community, including participation in the International Society for Environmental Epidemiology Meeting in August 2014.

References:

Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, Smith D. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environmental Science & Technology 2012;46(9):5118-5125, doi:10.1021/es203569f.

Eastman RR, Jursa TP, Benedetti C, Lucchini RG, Smith DR. Hair as a biomarker of environmental manganese exposure. Environmental Science & Technology 2013;47(3):1629-1637.


Journal Articles: 137 Displayed | Download in RIS Format

Other center views: All 666 publications 138 publications in selected types All 137 journal articles
Type Citation Sub Project Document Sources
Journal Article Alkon A, Boyce WT, Davis NV, Eskenazi B. Developmental changes in autonomic nervous system resting and reactivity measures in Latino children from 6 to 60 months of age. Journal of Developmental and Behavioral Pediatrics 2011;32(9):668-677. R834513 (2012)
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  • Journal Article Alkon A, Boyce WT, Tran L, Harley KG, Neuhaus J, Eskenazi B. Prenatal adversities and Latino children's autonomic nervous system reactivity trajectories from 6 months to 5 years of age. PLoS One 2014;9(1):e86283. R834513 (2012)
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  • Journal Article Alkon A, Harley KG, Neilands TB, Tambellini K, Lustig RH, Boyce WT, Eskenazi B. Latino children's body mass index at 2-3.5 years predicts sympathetic nervous system activity at 5 years. Childhood Obesity 2014;10(3):214-224. R834513 (2012)
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  • Journal Article Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, Smith D. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environmental Science & Technology 2012;46(9):5118-5125. R834513 (Final)
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  • Journal Article Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, Smith DR. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environmental Science & Technology 2012;46(9):5118-5125. R834513 (2010)
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  • Journal Article Audelo J, Kogut K, Harley KG, Rosas LG, Stein L, Eskenazi B. Maternal depression and childhood overweight in the CHAMACOS Study of Mexican-American children. Maternal and Child Health Journal 2016;20(7):1405-1414. R834513 (2014)
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  • Journal Article AugsJoost B, Jerman P, Deardorff J, Harley K, Constantine NA. Factors associated with parent support for condom education and availability. Health Education & Behavior 2014;41(2):207-215. R834513 (2014)
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  • Journal Article Austin C, Smith TM, Bradman A, Hinde K, Joannes-Boyau R, Bishop D, Hare DJ, Doble P, Eskenazi B, Arora M. Barium distributions in teeth reveal early-life dietary transitions in primates. Nature 2013;498(7453):216-219. R834513 (2013)
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  • Journal Article Beamer PI, Canales RA, Bradman A, Leckie JO. Farmworker children’s residential non-dietary exposure estimates from micro-level activity time series. Environment International 2009;35(8):1202-1209. R834513 (2010)
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  • Journal Article Beamer PI, Canales RA, Ferguson AC, Leckie JO, Bradman A. Relative pesticide and exposure route contribution to aggregate and cumulative dose in young farmworker children. International Journal of Environmental Research and Public Health 2012;9(1):73-96. R834513 (2013)
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  • Journal Article Beamer P, Canales RA, Leckie JO. Developing probability distributions for transfer efficiencies for dermal exposure. Journal of Exposure Science and Environmental Epidemiology 2009;19(3):274-283. R834513 (2010)
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  • Journal Article Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB, Eskenazi B. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environmental Health Perspectives 2011;119(8):1189-1195. R834513 (2010)
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  • Journal Article Bradman A, Fenster L, Sjodin A, Jones RS, Patterson Jr DG, Eskenazi B. Polybrominated diphenyl ether levels in the blood of pregnant women living in an agricultural community in California. Environmental Health Perspectives 2007;115(1):71-74. R834513 (2010)
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  • Journal Article Bradman A, Castorina R, Barr DB, Chevrier J, Harnly ME, Eisen EA, McKone TE, Harley K, Holland N, Eskenazi B. Determinants of organophosphorus pesticide urinary metabolite levels in young children living in an agricultural community. International Journal of Environmental Research and Public Health 2011;8(4):1061-1083. R834513 (2010)
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  • Journal Article Bradman A, Castorina R, Sjodin A, Fenster L, Jones RS, Harley KG, Chevrier J, Holland NT, Eskenazi B. Factors associated with serum polybrominated diphenyl ether (PBDE) levels among school-age children in the CHAMACOS cohort. Environmental Science & Technology 2012;46(13):7373-7381. R834513 (2012)
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  • Journal Article Bradman A, Kogut K, Eisen EA, Jewell NP, Quiros-Alcala L, Castorina R, Chevrier J, Holland NT, Barr DB, Kavanagh-Baird G, Eskenazi B. Variability of organophosphorous pesticide metabolite levels in spot and 24-hr urine samples collected from young children during 1 week. Environmental Health Perspectives 2013;121(1):118-124. R834513 (2011)
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  • Journal Article Bradman A, Castorina R, Gaspar F, Nishioka M, Colon M, Weathers W, Egeghy PP, Maddalena R, Williams J, Jenkins PL, McKone TE. Flame retardant exposures in California early childhood education environments. Chemosphere 2014;116:61-66. R834513 (2014)
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  • Journal Article Bradman A, Quiros-Alcala L, Castorina R, Schall RA, Camacho J, Holland NT, Barr DB, Eskenazi B. Effect of organic diet intervention on pesticide exposures in young children living in low-income urban and agricultural communities. Environmental Health Perspectives 2015;123(10):1086-1093. R834513 (2014)
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  • Journal Article Castorina R, Bradman A, Fenster L, Barr DB, Bravo R, Vedar MG, Harnly ME, McKone TE, Eisen EA, Eskenazi B. Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES. Environmental Health Perspectives 2010;118(6):856-863. R834513 (2010)
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  • Journal Article Castorina R, Bradman A, Sjodin A, Fenster L, Jones RS, Harley KG, Eisen EA, Eskenazi B. Determinants of serum polybrominated diphenyl ether (PBDE) levels among pregnant women in the CHAMACOS cohort. Environmental Science & Technology 2011;45(15):6553-6560. R834513 (2010)
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  • Journal Article Castorina R, Bradman A, Stapleton HM, Butt C, Avery D, Harley KG, Gunier RB, Holland N, Eskenazi B. Current-use flame retardants: maternal exposure and neurodevelopment in children of the CHAMACOS cohort. Chemosphere 2017;189:574-580. R834513 (Final)
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  • Journal Article Castorina R, Butt C, Stapleton HM, Avery D, Harley KG, Holland N, Eskenazi B, Bradman A. Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort). Chemosphere 2017;179:159-166. R834513 (Final)
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  • Journal Article Chadwick LH, Sawa A, Yang IV, Baccarelli A, Breakefield XO, Deng H-W, Dolinoy DC, Fallin MD, Holland NT, Houseman EA, Lomvardas S, Rao M, Satterlee JS, Tyson FL, Vijayanand P, Greally JM. New insights and updated guidelines for epigenome-wide association studies. Neuroepigenetics 2015;1:14-19. R834513 (2014)
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  • Journal Article Chevrier J, Harley KG, Bradman A, Gharbi M, Sjodin A, Eskenazi B. Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environmental Health Perspectives 2010;118(10):1444-1449. R834513 (2010)
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  • Journal Article Chevrier J, Harley KG, Bradman A, Sjodin A, Eskenazi B. Prenatal exposure to polybrominated diphenyl ether flame retardants and neonatal thyroid-stimulating hormone levels in the CHAMACOS study. American Journal of Epidemiology 2011;174(10):1166-1174. R834513 (2010)
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  • Journal Article Chevrier J, Harley KG, Kogut K, Holland N, Johnson C, Eskenazi B. Maternal thyroid function during the second half of pregnancy and child neurodevelopment at 6, 12, 24, and 60 months of age. Journal of Thyroid Research 2011;2011:426427 (13 pp.). R834513 (2011)
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  • Journal Article Chevrier J, Gunier RB, Bradman A, Holland NT, Calafat AM, Eskenazi B, Harley KG. Maternal urinary bisphenol A during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study. Environmental Health Perspectives 2013;121(1):138-144. R834513 (2012)
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  • Journal Article Chevrier J, Warner M, Gunier RB, Brambilla P, Eskenazi B, Mocarelli P. Serum dioxin concentrations and thyroid hormone levels in the Seveso Women’s Health Study. American Journal of Epidemiology 2014;180(5):490-498. R834513 (2014)
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  • Journal Article Chopra V, Harley K, Lahiff M, Eskenazi B. Association between phthalates and attention deficit disorder and learning disability in U.S. children, 6-15 years. Environmental Research 2014;128:64-69. R834513 (2014)
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  • Journal Article Coker E, Gunier R, Bradman A, Harley K, Kogut K, Molitor J, Eskenazi B. Association between Pesticide Profiles Used on Agricultural Fields near Maternal Residences during Pregnancy and IQ at Age 7 Years. International Journal of Environmental Research and Public Health 2017;14(5):506 (20 pp.). R834513 (Final)
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  • Journal Article Dannemiller KC, Mendell MJ, Macher JM, Kumagai K, Bradman A, Holland N, Harley K, Eskenazi B, Peccia J. Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development. Indoor Air 2014;24(3):236-247. R834513 (2014)
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  • Journal Article Dave V, Yousefi P, Huen K, Volberg V, Holland N. Relationship between expression and methylation of obesity-related genes in children. Mutagenesis 2015;30(3):411-420. R834513 (2013)
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  • Journal Article Dave V, Street K, Francis S, Bradman A, Riley L, Eskenazi B, Holland N. Bacterial microbiome of breast milk and child saliva from low-income Mexican-American women and children. Pediatric Research 2016;79(6):846-854. R834513 (Final)
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  • Journal Article Duramad P, Holland NT. Biomarkers of immunotoxicity for environmental and public health research. International Journal of Environmental Research and Public Health 2011;8(5):1388-1401. R834513 (2010)
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  • Journal Article Eastman RR, Jursa TP, Benedetti C, Lucchini RG, Smith DR. Hair as a biomarker of environmental manganese exposure. Environmental Science & Technology 2013;47(3):1629-1637. R834513 (2012)
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  • Journal Article Ehrlich SF, Rosas LG, Ferrara A, King JC, Abrams B, Harley KG, Hedderson MM, Eskenazi B. Pregnancy glucose levels in women without diabetes or gestational diabetes and childhood cardiometabolic risk at 7 years of age. Journal of Pediatrics 2012;161(6):1016-1021. R834513 (2012)
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  • Journal Article Ehrlich SF, Rosas LG, Ferrara A, King JC, Abrams B, Harley KG, Hedderson MM, Eskenazi B. Pregnancy glycemia in Mexican-American women without diabetes or gestational diabetes and programming for childhood obesity. American Journal of Epidemiology 2013;177(8):768-775. R834513 (2012)
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  • Journal Article Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environmental Health Perspectives 2016;124(6):822-830. R834513 (2014)
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  • Journal Article Erkin-Cakmak A, Harley KG, Chevrier J, Bradman A, Kogut K, Huen K, Eskenazi B. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS Study. Environmental Health Perspectives 2015;123(6):636-642. R834513 (2015)
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  • Journal Article Eskenazi B, Huen K, Marks A, Harley KG, Bradman A, Barr DB, Holland N. PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero. Environmental Health Perspectives 2010;118(12):1775-1781. R834513 (2010)
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  • Journal Article Eskenazi B, Fenster L, Castorina R, Marks AR, Sjodin A, Rosas LG, Holland N, Guerra AG, Lopez-Carrillo L, Bradman A. A comparison of PBDE serum concentrations in Mexican and Mexican-American children living in California. Environmental Health Perspectives 2011;119(10):1442-1448. R834513 (2010)
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  • Journal Article Eskenazi B, Chevrier J, Rauch SA, Kogut K, Harley KG, Johnson C, Trujillo C, Sjodin A, Bradman A. In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. Environmental Health Perspectives 2013;121(2):257-262. R834513 (2012)
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  • Journal Article Eskenazi B, Bradman A, Finkton D, Purwar M, Noble JA, Pang R, Burnham O, Cheikh Ismail L, Farhi F, Barros FC, Lambert A, Papageorghiou AT, Carvalho M, Jaffer YA, Bertino E, Gravett MG, Altman DG, Ohuma EO, Kennedy SH, Bhutta ZA, Villar J, International Fetal and Newborn Growth Consortium for the 21st Century. A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project. BJOG: An International Journal of Obstetrics & Gynaecology 2013;120(Suppl 2):129-138. R834513 (2014)
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  • Journal Article Eskenazi B, Warner M, Sirtori M, Fuerst T, Rauch SA, Brambilla P, Mocarelli P, Rubinacci A. Serum dioxin concentrations and bone density and strucure in the Seveso Women’s Health Study. Environmental Health Perspectives 2014;122(1):51-57. R834513 (2014)
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  • Journal Article Eskenazi B, Quiros-Alcala L, Lipsitt JM, Wu LD, Kruger P, Ntimbane T, Nawn JB, Bornman R, Seto E. mSpray: a mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo, South Africa. Environment International 2014;68:219-226. R834513 (2014)
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  • Journal Article Eskenazi B, Kogut K, Huen K, Harley KG, Bouchard M, Bradman A, Boyd-Barr D, Johnson C, Holland N. Organophosphate pesticide exposure, PON1, and neurodevelopment in school-age children from the CHAMACOS study. Environmental Research 2014;134:149-157. R834513 (2014)
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  • Journal Article Eskenazi B, Rauch SA, Tenerelli R, Huen K, Holland NT, Lustig RH, Kogut K, Bradman A, Sjödin A, Harley KG. In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: the CHAMACOS study. International Journal of Hygiene and Environmental Health 2017;220(2 Pt B):364-372. R834513 (Final)
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  • Journal Article Gaspar FW, Castorina R, Maddalena RL, Nishioka MG, McKone TE, Bradman A. Phthalate exposure and risk assessment in California child care facilities. Environmental Science & Technology 2014;48(13):7593-7601. R834513 (2014)
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  • Journal Article Gaspar FW, Harley KG, Kogut K, Chevrier J, Mora AM, Sjodin A, Eskenazi B. Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort. Environment International 2015;85:206-212. R834513 (2014)
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  • Journal Article Gemmill A, Gunier RB, Bradman A, Eskenazi B, Harley KG. Residential proximity to methyl bromide use and birth outcomes in an agricultural population in California. Environmental Health Perspectives 2013;121(6):737-743. R834513 (2013)
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  • Journal Article Gomez N, Guendelman S, Harley KG, Gomez SL. Nativity and neighborhood characteristics and cervical cancer stage at diagnosis and survival outcomes among Hispanic women in California. American Journal of Public Health 2015;105(3):538-545. R834513 (Final)
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  • Journal Article Guerrero J, Madrigal DS, Minkler M. What is…?: a research ethics Jeopardy™ game to help community partners understand human subjects protections and their importance. Progress in Community Health Partnerships: Research, Education, and Action 2014;8(3):405-411. R834513 (2014)
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  • Journal Article Gunier RB, Bradman A, Jerrett M, Smith DR, Harley KG, Austin C, Vedar M, Arora M, Eskenazi B. Determinants of manganese in prenatal dentin of shed teeth from CHAMACOS children living in an agricultural community. Environmental Science & Technology 2013;47(19):11249-11257. R834513 (2013)
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  • Journal Article Gunier RB, Mora AM, Smith D, Arora M, Austin C, Eskenazi B, Bradman A. Biomarkers of manganese exposure in pregnant women and children living in an agricultural community in California. Environmental Science & Technology 2014;48(24):14695-14702. R834513 (2011)
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  • Journal Article Gunier RB, Jerrett M, Smith DR, Jursa T, Yousefi P, Camacho J, Hubbard A, Eskenazi B, Bradman A. Determinants of manganese levels in house dust samples from the CHAMACOS cohort. Science of the Total Environment 2014;497-498:360-368. R834513 (2012)
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  • Journal Article Gunier RB, Arora M, Jerrett M, Bradman A, Harley KG, Mora AM, Kogut K, Hubbard A, Austin C, Holland N, Eskenazi B. Manganese in teeth and neurodevelopment in young Mexican-American children. Environmental Research 2015;142:688-695. R834513 (2014)
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  • Journal Article Gunier RB, Bradman A, Harley KG, Eskenazi B. Will buffer zones around schools in agricultural areas be adequate to protect children from the potential adverse effects of pesticide exposure? PLoS Biology 2017;15(12):e2004741 (7 pp.). R834513 (Final)
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  • Journal Article Gunier RB, Bradman A, Harley KG, Kogut K, Eskenazi B. Prenatal residential proximity to agricultural pesticide use and IQ in 7-year-old children. Environmental Health Perspectives 2017;125(5):057002 (8 pp.). R834513 (Final)
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  • Journal Article Gunier RB, Bradman A, Castorina R, Holland NT, Avery D, Harley KG, Eskenazi B. Residential proximity to agricultural fumigant use and IQ, attention and hyperactivity in 7-year old children. Environmental Research 2017;158:358-365. R834513 (Final)
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  • Journal Article Gunier RB, Raanan R, Castorina R, Holland NT, Harley KG, Balmes JR, Fouquette L, Eskenazi B, Bradman A. Residential proximity to agricultural fumigant use and respiratory health in 7-year old children. Environmental Research. 2018;164:93-99. R834513 (Final)
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  • Journal Article Harley KG, Marks AR, Chevrier J, Bradman A, Sjodin A, Eskenazi B. PBDE concentrations in women’s serum and fecundability. Environmental Health Perspectives 2010;118(5):699-704. R834513 (2010)
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  • Journal Article Harley KG, Huen K, Aguilar Schall R, Holland NT, Bradman A, Barr DB, Eskenazi B. Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women. PLoS ONE 2011;6(8):e23923 (10 pp.). R834513 (2010)
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  • Journal Article Harley KG, Chevrier J, Schall RA, Sjodin A, Bradman A, Eskenazi B. Association of prenatal exposure to polybrominated diphenyl ethers and infant birth weight. American Journal of Epidemiology 2011;174(8):885-892. R834513 (2010)
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  • Journal Article Harley KG, Aguilar Schall R, Chevrier J, Tyler K, Aguirre H, Bradman A, Holland NT, Lustig RH, Calafat AM, Eskenazi B. Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environmental Health Perspectives 2013;121(4):514-520. R834513 (2012)
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  • Journal Article Harley KG, Gunier RB, Kogut K, Johnson C, Bradman A, Calafat AM, Eskenazi B. Prenatal and early childhood bisphenol A concentrations and behavior in school-aged children. Environmental Research 2013;126:43-50. R834513 (2014)
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  • Journal Article Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. Prenatal exposure to organophosphate pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environmental Health Perspectives 2016;124(7):1084-1092. R834513 (2014)
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  • Journal Article Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environmental Health Perspectives 2016;124(7):1084-1092. R834513 (Final)
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  • Journal Article Harley KG, Kogut K, Madrigal DS, Cardenas M, Vera IA, Meza-Alfaro G, She J, Gavin Q, Zahedi R, Bradman A, Eskenazi B, Parra KL. Reducing phthalate, paraben, and phenol exposure from personal care products in adolescent girls: findings from the HERMOSA Intervention Study. Environmental Health Perspectives 2016;124(10):1600-1607. R834513 (Final)
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  • Journal Article Harley KG, Rauch SA, Chevrier J, Kogut K, Parra KL, Trujillo C, Lustig RH, Greenspan LC, Sjodin A, Bradman A, Eskenazi B. Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls. Environment International 2017;100:132-138. R834513 (2014)
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  • Journal Article Harley KG, Berger K, Rauch S, Kogut K, Henn BC, Calafat AM, Huen K, Eskenazi B, Holland N. Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatric Research 2017;82(3):405-415. R834513 (Final)
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  • Journal Article Harnly ME, Bradman A, Nishioka M, McKone TE, Smith D, McLaughlin R, Kavanagh-Baird G, Castorina R, Eskenazi B. Pesticides in dust from homes in an agricultural area. Environmental Science & Technology 2009;43(23):8767-8774. R834513 (2010)
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  • Journal Article Heggeseth B, Harley K, Warner M, Jewell N, Eskenazi B. Detecting associations between early-life DDT exposures and childhood growth patterns: a novel statistical approach. PLoS ONE 2015;10(6):e0131443 (13 pp.). R834513 (2015)
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  • Journal Article Holland N, Lizarraga D, Huen K. Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children's environmental health. Current Opinion in Pediatrics 2015;27(2):240-247. R834513 (2013)
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  • Journal Article Holland N, Huen K, Tran V, Street K, Nguyen B, Bradman A, Eskenazi B. Urinary phthalate metabolites and biomarkers of oxidative stress in a Mexican-American cohort: variability in early and late pregnancy. Toxics 2016;4(1):7 (18 pp.). R834513 (Final)
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  • Journal Article Huen K, Richter R, Furlong C, Eskenazi B, Holland N. Validation of PON1 enzyme activity assays for longitudinal studies. Clinica Chimica Acta 2009;402(1-2):67-74. R834513 (2010)
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  • Journal Article Huen K, Harley K, Brooks J, Hubbard A, Bradman A, Eskenazi B, Holland N. Developmental changes in PON1 enzyme activity in young children and effects of PON1 polymorphisms. Environmental Health Perspectives 2009;117(10):1632-1638. R834513 (2010)
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  • Journal Article Huen K, Harley K, Bradman A, Eskenazi B, Holland N. Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and children with different genotypes and haplotypes. Toxicology and Applied Pharmacology 2010;244(2):181-189. R834513 (2010)
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  • Journal Article Huen K, Barcellos L, Beckman K, Rose S, Eskenazi B, Holland N. Effects of PON polymorphisms and haplotypes on molecular phenotype in Mexican-American mothers and children. Environmental and Molecular Mutagenesis 2011;52(2):105-116. R834513 (2010)
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  • Journal Article Huen K, Bradman A, Harley K, Yousefi P, Boyd Barr D, Eskenazi B, Holland N. Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community. Environmental Research 2012;117:8-16. R834513 (2010)
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  • Journal Article Huen K, Harley K, Beckman K, Eskenazi B, Holland N. Associations of PON1 and genetic ancestry with obesity in early childhood. PLoS One 2013;8(5):e62565. R834513 (2013)
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  • Journal Article Huen K, Yousefi P, Bradman A, Yan L, Harley KG, Kogut K, Eskenazi B, Holland N. Effects of age, sex, and persistent organic pollutants on DNA methylation in children. Environmental and Molecular Mutagenesis 2014;55(3):209-222. R834513 (2012)
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  • Journal Article Huen K, Yousefi P, Street K, Eskenazi B, Holland N. PON1 as a model for integration of genetic, epigenetic, and expression data on candidate susceptibility genes. Environmental Epigenetics 2015;1(1):dvv003. R834513 (2015)
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  • Journal Article Huen K, Calafat AM, Bradman A, Yousefi P, Eskenazi B, Holland N. Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children. Environmental Research 2016;148:55-62. R834513 (Final)
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  • Journal Article Huen K, Harley K, Kogut K, Rauch S, Eskenazi B, Holland N. DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. Pediatric Research 2016;79(6):855-862. R834513 (2014)
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  • Journal Article Johnson M, Deardorff J, Davis EL, Martinez W, Eskenazi B, Alkon A. The relationship between maternal responsivity, socioeconomic status, and resting autonomic nervous system functioning in Mexican American children. International Journal of Psychophysiology 2017;116:45-52. R834513 (Final)
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  • Journal Article Lizarraga D, Huen K, Combs M, Escudero-Fung M, Eskenazi B, Holland N. miRNAs differentially expressed by next-generation sequencing in cord blood buffy coat samples of boys and girls. Epigenomics 2016;8(12):1619-1635. R834513 (Final)
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  • Journal Article Lopez-Espinosa M-J, Mondal D, Armstrong BG, Eskenazi B, Fletcher T. Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6-9 years of age: a cross-sectional analysis within the C8 Health Project. Environmental Health Perspectives 2016;124(8):1269-1275. R834513 (2014)
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  • Journal Article Macher JM, Mendell MJ, Kumagai K, Holland NT, Camacho JM, Harley KG, Eskenazi B, Bradman A. Higher measured moisture in California homes with qualitative evidence of dampness. Indoor Air 2016;26(6):892-902. R834513 (Final)
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  • Journal Article Madrigal DS, Salvatore A, Casillas G, Casillas C, Vera I, Eskenazi B, Minkler M. Health in my community: conducting and evaluating PhotoVoice as a tool to promote environmental health and leadership among Latino/a youth. Progress in Community Health Partnerships: Research, Education, and Action 2014;8(3):317-329. R834513 (2014)
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  • Journal Article Marks AR, Harley K, Bradman A, Kogut K, Barr DB, Johnson C, Calderon N, Eskenazi B. Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS Study. Environmental Health Perspectives 2010;118(12):1768-1774. R834513 (2010)
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  • Journal Article Mora AM, van Wendel de Joode B, Mergler D, Cordoba L, Cano C, Quesada R, Smith DR, Menezes-Filho JA, Lundh T, Lindh CH, Bradman A, Eskenazi B. Blood and hair manganese concentrations in pregnant women from the Infants’ Environmental Health Study (ISA) in Costa Rica. Environmental Science & Technology 2014;48(6):3467-3476. R834513 (2014)
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  • Journal Article Mora AM, van Wendel de Joode B, Mergler D, Cordoba L, Cano C, Quesada R, Smith DR, Menezes-Filho JA, Eskenazi B. Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica. Environmental Research 2015;136:47-56. R834513 (2014)
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  • Journal Article Mora AM, Arora M, Harley KG, Kogut K, Parra K, Hernandez-Bonilla D, Gunier RB, Bradman A, Smith DR, Eskenazi B. Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and 10.5 years in the CHAMACOS cohort. Environment International 2015;84:39-54. R834513 (2014)
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  • Journal Article Payne-Sturges D, Cohen J, Castorina R, Axelrad DA, Woodruff TJ. Evaluating cumulative organophosphorus pesticide body burden of children: a national case study. Environmental Science & Technology 2009;43(20):7924-7930. R834513 (2010)
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  • Journal Article Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, Eskenazi B. Concentrations and loadings of polybrominated diphenyl ethers in dust from low-income households in California. Environment International 2011;37(3):592-596. R834513 (2010)
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  • Journal Article Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, Ferber J, Eskenazi B. Pesticides in house dust from urban and farmworker households in California: an observational measurement study. Environmental Health 2011;10:19 (15 pp.). R834513 (2010)
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  • Journal Article Quiros-Alcala L, Alkon AD, Boyce WT, Lippert S, Davis NV, Bradman A, Barr DB, Eskenazi B. Maternal prenatal and child organophosphate pesticide exposures and children's autonomic function. NeuroToxicology 2011;32(5):646-655. R834513 (2010)
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  • Journal Article Quiros-Alcala L, Bradman A, Smith K, Weerasekera G, Odetokun M, Barr DB, Nishioka M, Castorina R, Hubbard AE, Nicas M, Hammond SK, McKone TE, Eskenazi B. Organophosphorous pesticide breakdown products in house dust and children's urine. Journal of Exposure Science & Environmental Epidemiology 2012;22(6):559-568. R834513 (2012)
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  • Journal Article Quiros-Alcala L, Eskenazi B, Bradman A, Ye X, Calafat AM, Harley K. Determinants of urinary bisphenol A concentrations in Mexican/Mexican-American pregnant women. Environment International 2013;59:152-160. R834513 (2013)
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  • Journal Article Quiros-Alcala L, Mehta S, Eskenazi B. Pyrethroid pesticide exposure and parental report of learning disability and attention deficit/hyperactivity disorder in U.S. children: NHANES 1999-2002. Environmental Health Perspectives 2014;122(12):1336-1342. R834513 (2014)
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  • Journal Article Raanan R, Harley KG, Balmes JR, Bradman A, Lipsett M, Eskenazi B. Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort. Environmental Health Perspectives 2015;123(2):179-185. R834513 (2010)
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  • Journal Article Raanan R, Balmes JR, Harley KG, Gunier RB, Magzamen S, Bradman A, Eskenazi B. Decreased lung function in 7-year-old children with early-life organophosphate exposure. Thorax 2016;71(2):148-153. R834513 (2015)
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    R834513C001 (2014)
    R834513C001 (2015)
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  • Journal Article Raanan R, Gunier RB, Balmes JR, Beltran AJ, Harley KG, Bradman A, Eskenazi B. Elemental sulfur use and associations with pediatric lung function and respiratory symptoms in an agricultural community (California, USA). Environmental Health Perspectives 2017;125(8):087007 (8 pp.). R834513 (Final)
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  • Journal Article Rosas LG, Harley K, Fernald LC, Guendelman S, Mejia F, Neufeld LM, Eskenazi B. Dietary associations of household food insecurity among children of Mexican descent: results of a binational study. Journal of the American Dietetic Association 2009;109(12):2001-2009. R834513 (2010)
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  • Journal Article Rosas LG, Harley KG, Guendelman S, Fernald LC, Mejia F, Eskenazi B. Maternal perception of child weight among Mexicans in California and Mexico. Maternal and Child Health Journal 2010;14(6):886-894. R834513 (2010)
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  • Journal Article Rosas LG, Guendelman S, Harley K, Fernald LC, Neufeld L, Mejia F, Eskenazi B. Factors associated with overweight and obesity among children of Mexican descent:results of a binational study. Journal of Immigrant and Minority Health 2011;13(1):169-180. R834513 (2010)
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  • Journal Article Rosas LG, Trujillo C, Camacho J, Madrigal D, Bradman A, Eskenazi B. Acceptability of health information technology aimed at environmental health education in a prenatal clinic. Patient Education and Counseling 2014;97(2):244-247. R834513 (2014)
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  • Journal Article Rowe C, Gunier R, Bradman A, Harley KG, Kogut K, Parra K, Eskenazi B. Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children. Environmental Research 2016;150:128-137. R834513 (2015)
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  • Journal Article Sagiv SK, Kogut K, Gaspar FW, Gunier RB, Harley KG, Parra K, Villasenor D, Bradman A, Holland N, Eskenazi B. Prenatal and childhood polybrominated diphenyl ether (PBDE) exposure and attention and executive function at 9-12 years of age. Neurotoxicology and Teratology 2015:52(Pt B):151-161. R834513 (2014)
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  • Journal Article Salvatore AL, Chevrier J, Bradman A, Camacho J, Lopez J, Kavanagh-Baird G, Minkler M, Eskenazi B. A community-based participatory worksite intervention to reduce pesticide exposures to farmworkers and their families. American Journal of Public Health 2009;99(Suppl 3):S578-S581. R834513 (2010)
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  • Journal Article Salvatore AL, Castorina R, Camacho J, Morga N, Lopez J, Nishioka M, Barr DB, Eskenazi B, Bradman A. Home-based community health worker intervention to reduce pesticide exposures to farmworkers’ children: a randomized-controlled trial. Journal of Exposure Science & Environmental Epidemiology 2015;25(6):608-615. R834513 (2014)
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  • Journal Article Scholtz, RI, McLaughlin KR, Cirillo PM, Petreas M, Park J-S, Wolff MS, Factor-Litvak P, Eskenazi B, Krigbaum N, Cohn BA. Assaying organochlorines in archived serum for a large, long-term cohort:implications of combining assay results from multiple laboratories over time. Environment International 2011;37(4):709-714. R834513 (2010)
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  • Journal Article Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, Van Wely M, Cao J, Martini AC, Eskandar M, Chavarro JE, Koloszar S, Twigt JM, Ramlau-Hansen CH, Borges Jr. E, Lotti F, Steegers-Theunissen RPM, Zorn B, Polotsky AJ, La Vignera S, Eskenazi B, Tremellen K, Magnusdottir EV, Fejes I, Hercberg S, Levy R, Czernichow S. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Human Reproduction Update 2013;19(3):221-231. R834513 (2014)
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  • Journal Article Sjodin A, Jones RS, Gunier RB, Wong LY, Holland N, Eskenazi B, Bradman, A. Polybrominated diphenyl ethers, polychlorinated biphenyls, and 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene in 7-and 9-year-old children and their mothers in the Center for the Health Assessment of Mothers and Children of Salinas Cohort. Environmental Science & Technology 2018;52(4):2287-2294. R834513 (Final)
    R834513C002 (2015)
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  • Journal Article Sly PD Eskenazi B, Pronczuk J, Sram R, Diaz-Barriga F, Machin DG, Carpenter DO, Surdu S, Meslin EM. Ethical issues in measuring biomarkers in children's environmental health. Environmental Health Perspectives 2009;117(8):1185-1190. R834513 (2010)
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  • Journal Article Solomon O, Yousefi P, Huen K, Gunier RB, Escudero-Fung M, Barcellos LF, Eskenazi B, Holland N. Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood. Environmental and Molecular Mutagenesis 2017;58(6):398-410. R834513 (Final)
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  • Journal Article Stein LJ, Gunier RB, Harley K, Kogut K, Bradman A, Eskenazi B. Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: the CHAMACOS cohort. Neurotoxicology 2016;56:180-187. R834513 (2015)
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  • Journal Article Torres JM, Deardorff J, Gunier RB, Harley KG, Alkon A, Kogut K, Eskenazi B. Worry about deportation and cardiovascular disease risk factors among adult women: the Center for the Health Assessment of Mothers and Children of Salinas Study. Annals of Behavioral Medicine 2018;52(2):186-193. R834513 (Final)
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  • Journal Article Tran V, Tindula G, Huen K, Bradman A, Harley K, Kogut K, Calafat AM, Nguyen B, Parra K, Ye X, Eskenazi B, Holland N. Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity. Journal of Developmental Origins of Health and Disease 2017;8(2):196-205. R834513 (Final)
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  • Journal Article van Wendel de Joode B, Mora AM, Cordoba L, Cano JC, Quesada R, Faniband M, Wesseling C, Ruepert C, Oberg M, Eskenazi B, Mergler D, Lindh CH. Aerial application of mancozeb and urinary ethylene thiourea (ETU) concentrations among pregnant women in Costa Rica: the Infants’ Environmental Health Study (ISA). Environmental Health Perspectives 2014;122(12):1321-1328. R834513 (2014)
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  • Journal Article Verner M-A, Gaspar FW, Chevrier J, Gunier RB, Sjodin A, Bradman A, Eskenazi B. Increasing sample size in prospective birth cohorts:back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children. Environmental Science & Technology 2015;49(6):3940-3948. R834513 (2014)
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  • Journal Article Volberg V, Harley KG, Aguilar RS, Rosas LG, Huen K, Yousefi P, Dave V, Phan N, Lustig RH, Eskenazi B, Holland N. Associations between perinatal factors and adiponectin and leptin in 9-year-old Mexican-American children. Pediatric Obesity 2013;8(6):454-463. R834513 (2013)
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  • Journal Article Volberg V, Heggeseth B, Harley K, Huen K, Yousefi P, Dave V, Tyler K, Vedar M, Eskenazi B, Holland N. Adiponectin and leptin trajectories in Mexican-American children from birth to 9 years of age. PLoS One 2013;8(10):e77964 (8 pp.). R834513 (2014)
    R834513C003 (2014)
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  • Journal Article Volberg V, Harley K, Calafat AM, Dave V, McFadden J, Eskenazi B, Holland N. Maternal bisphenol A exposure during pregnancy and its association with adipokines in Mexican-American children. Environmental and Molecular Mutagenesis 2013;54(8):621-628. R834513 (2014)
    R834513C001 (2014)
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  • Journal Article Warner M, Mocarelli P, Brambilla P, Wesselink A, Samuels S, Signorini S, Eskenazi B. Diabetes, metabolic syndrome, and obesity in relation to serum dioxin concentrations: the Seveso Women's Health Study. Environmental Health Perspectives 2013;121(8):906-911. R834513 (2013)
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  • Journal Article Warner M, Schall RA, Harley KG, Bradman A, Barr D, Eskenazi B. In utero DDT and DDE exposure and obesity status of 7-year-old Mexican-American children in the CHAMACOS cohort. Environmental Health Perspectives 2013;121(5):631-636. R834513 (2013)
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  • Journal Article Warner M, Wesselink A, Harley KG, Bradman A, Kogut K, Eskenazi B. Prenatal exposure to dichlorodiphenyltrichloroethane and obesity at 9 years of age in the CHAMACOS Study cohort. American Journal of Epidemiology 2014;179(11):1312-1322. R834513 (2014)
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  • Journal Article Warner M, Mocarelli P, Brambilla P, Wesselink A, Patterson Jr. DG, Turner WE, Eskenazi B. Serum TCDD and TEQ concentrations among Seveso women, 20 years after the explosion. Journal of Exposure Science & Environmental Epidemiology 2014;24(6):588-594. R834513 (2014)
    R834513C002 (2014)
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  • Journal Article Warner M, Ye M, Harley K, Kogut K, Bradman A, Eskenazi B. Prenatal DDT exposure and child adiposity at 12 years of age in the CHAMACOS cohort. Environmental Research 2017;159:606-612. R834513 (Final)
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  • Journal Article Waters SF, Boyce WT, Eskenazi B, Alkon A. The impact of maternal depression and overcrowded housing on associations between autonomic nervous system reactivity and externalizing behavior problems in vulnerable Latino children. Psychophysiology 2016;53(1):97-104. R834513 (Final)
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  • Journal Article Weerasekera G, Smith KD, Quiros-Alcala L, Fernandez C, Bradman A, Eskenazi B, Needham LL, Barr DB. A mass spectrometry-based method to measure dialkylphosphate degradation products of organophosphorous insecticides in dust and orange juice. Journal of Environmental Monitoring 2009;11(7):1345-1351. R834513 (2010)
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  • Journal Article Weldon RH, Webster M, Harley KG, Bradman A, Fenster L, Davis MD, Hubbard A, Barr DB, Holland N, Eskenazi B. Serum persistent organic pollutants and duration of lactation among Mexican-American women. Journal of Environmental and Public Health 2010;2010:861757 (11 pp.). R834513 (2010)
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  • Journal Article Weldon RH, Barr DB, Trujillo C, Bradman A, Holland N, Eskenazi B. A pilot study of pesticides and PCBs in the breast milk of women residing in urban and agricultural communities of California. Journal of Environmental Monitoring 2011;13(11):3136-3144. R834513 (2011)
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  • Journal Article Wesselink A, Warner M, Samuels S, Parigi A, Brambilla P, Mocarelli P, Eskenazi B. Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in Seveso. Environment International 2014;63:143-148. R834513 (2014)
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  • Journal Article Yousefi P, Huen K, Schall RA, Decker A, Elboudwarej E, Quach H, Barcellos L, Holland N. Considerations for normalization of DNA methylation data by Illumina 450K BeadChip assay in population studies. Epigenetics 2013;8(11):1141-1152. R834513 (2012)
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  • Journal Article Yousefi P, Huen K, Quach H, Motwani G, Hubbard A, Eskenazi B, Holland N. Estimation of blood cellular heterogeneity in newborns and children for epigenome-wide association studies. Environmental and Molecular Mutagenesis 2015;56(9):751-758. R834513 (2015)
    R834513C003 (2015)
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  • Journal Article Yousefi P, Huen K, Dave V, Barcellos L, Eskenazi B, Holland N. Sex differences in DNA methylation assessed by 450 K BeadChip in newborns. BMC Genomics 2015;16:911. R834513C003 (2015)
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  • Supplemental Keywords:

    DDT, DDE, PBDEs, flame retardants, manganese, maneb, puberty, neurodevelopment, behavior, children’s health, CHAMACOS, mancozeb, pesticides, exposure assessment, biomonitoring, house dust, dust loading, teeth, blood, urine measurements, epigenetics, methylation, community outreach and translation, community-based research, environmental justice, farmworkers

    Relevant Websites:

    Berkeley Center for Environmental Research and Children's Health (CERCH) Exit
    Environmental Exposures in Child Care Facilities Study Exit
    Green Cleaning, Sanitizing, and Disinfecting: A Curriculum for Early Care and Education (PDF) Exit (68pp, 2.39MB)

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2015 Progress Report
  • Final Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834513C001 CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
    R834513C002 Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
    R834513C003 Epigenetics Project
    R834513C004 Community Outreach and Translation Core