Grantee Research Project Results
Final Report: Epigenetics Project
EPA Grant Number: R834513C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834513
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Epigenetics Project
Investigators: Eskenazi, Brenda
Institution: University of California - Berkeley
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2017)
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Over the past 20 years, the Center for Children’s Environmental Health Research at the University of California, Berkeley has successfully created and coordinated a transdisciplinary research program that addresses the unique environmental health needs of children living in a predominantly Latino farmworker community. Below is a summary of our many accomplishments since 2010 for the three Projects and an update on Cores.
Summary/Accomplishments (Outputs/Outcomes):
Our data collection work on this grant is complete, but we continue to work with data generated from this funding. We are currently preparing a manuscript for publication showing striking, sex-differentiated associations between prenatal OP pesticide exposures and children’s executive functioning and attention between ages 7 and 12. These indicate that boys experience pronounced deficits in maternally-reported executive function and child-assessed working memory in association with in utero OP exposure. We are also beginning work on analyses focused on the timing and tempo of puberty in CHAMACOS boys and girls, both as an outcome of early childhood adversity and as a predictor of risk-taking behavior in later adolescence. We expect to continue working with these data for years to come.
This portion of our Center grant set out to assess effects on boys’ neurodevelopment and pubertal development of prenatal and early life exposure to environmental exposures with wide U.S. and global relevance. We recognized that our Center was well poised to address societal concerns that environmental exposures could contribute to apparent increases in neurobehavioral issues like attention problems and a shifting age at puberty, and through our specific aims, we intended to do so. We have made important progress towards these aims. With regards to neurodevelopment, we have presented evidence of association between multiple early-life exposures and adverse neurobehavioral outcomes at this age point, particularly for boys. While prenatal PBDE exposure, prenatal methyl bromide and chloropicrin and early postnatal Mn exposure show similarly adverse associations with attention, executive functioning, and/or behavior for boys and girls, we provide evidence that prenatal Mn exposure and OP pesticide exposure (not yet published) may be particularly detrimental to boys. In so far as WISC Processing Speed and Working Memory Indices reflect attention and executive functioning capacities, respectively, our research suggests that prenatal DDT exposure and exposure to alternate flame retardants (Firemaster 500 or OP-based formulations) may also exert detrimental impacts on these outcomes. With regards to timing of puberty, we have provided evidence that PBDES, PCB, and DDT/E are associated with either earlier physical manifestations of male puberty or higher levels of male sex hormones at age 12. Early Mn exposure appears to be associated with slightly later genital development in boys, but was not associated with age 12 sex hormones (not published). In our parallel analyses of female pubertal timing, prenatal DDT exposure and early Mn exposure were associated with earlier menarche and earlier pubarche, respectively (not yet published). By contrast, prenatal PBDEs were associated with later menarche.
As noted above, the data collected under this grant and previous EPA funding have also enabled important research on other health outcomes of widespread interest in the U.S.: respiratory health and obesity. With regards to respiratory health, we observed associations between higher average urinary OP metabolite concentrations during childhood and increased respiratory symptoms and poorer lung function at 7-years of age. We also observed relationships between higher agricultural use of sulfur within 1 km of the child’s residence during the year prior to the 7-year visit and increased odds of reporting respiratory symptoms and poorer lung function. An important difference between the associations that we have observed with respiratory health and those with neurodevelopment is that postnatal pesticide exposures during early childhood appear to be more strongly related to adverse respiratory outcomes, whereas prenatal exposures consistently show stronger associations with neurodevelopmental outcomes. We did not observe any adverse relationship between prenatal or postnatal residential proximity to agricultural fumigant use and respiratory health in the CHAMACOS cohort. With regards to obesity, we’ve shown differential impacts of prenatal exposure to PBDEs and DDT/E based on child sex. Boys with higher prenatal exposure to PBDEs, DDT, and/or DDE all showed higher BMI in middle childhood, whereas girls with higher PBDE exposure tended to have a lower BMI in middle childhood (and showed no change in BMI linked to DDT/E exposure). One PBDE congener (BDE-153) as measured at age 7 was associated with lower BMI for both sexes at this age.
Novel epigenetic findings on the molecular mechanisms associated with environmental exposures in newborns and children resulting from the CHAMACOS Project C were only possible because of the existing CHAMACOS birth cohort data and banked biological samples collected over the children’s lifetime going back 18 years to the time when CHAMACOS children were in utero. This project required a careful examination of existing methodological and analytical approaches. We conducted a direct comparison of DNA methylation in different cell types that demonstrated that the commonly used minfi procedure may not be appropriate for newborns that have a different blood cell composition than adults. We developed novel methods of data normalization of high-dimensional genome-wide methylation data that was submitted to the public domain. We employed state-of the art analytical tools such as SuperLearner for statistical analyses and are now applying these methods in other studies.
Our data show striking differences in genome-wide DNA methylation by age and sex, not limited to CpG sites located in sex chromosomes. These findings provide additional evidence for the need to expand research on environmental epigenetics to a wide variety of sub-populations, including fetuses and pregnant women and minority cohorts (e.g. CHAMACOS) in order to explain differential risks and health effects. We first reported data from our birth cohort demonstrating that prenatal exposure to POPs such as PBDE and DDT that are still common in California and many other parts of the world and may be linked to hypomethylation in fetal blood. Importantly, we showed that accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies. These findings are immediately relevant to the EPA priority science question “What chemicals and combinations of chemicals… pose the greatest risk to children’s health”.
In short, within our Center, we have been able to trace important linkages between children’s early environmental exposures and multiple facets of their health and development in childhood. Beyond our Center, we’ve sought opportunities to contribute to collaborative investigations of these issues. In 2016, the CHAMACOS Study was selected to participate in the NIH-funded ECHO program (ECHO stands for Environmental influences on Child Health Outcomes), which has set out to construct a “synthetic cohort” of 50,000 US children by combining and harmonizing data collected from a large number of new and extant birth cohort studies around the country. Our participation in ECHO will facilitate use of CHAMACOS data – including data collected under this EPA funding – in any number of analyses related to children’s health and development.
Conclusions:
In Project C, we investigated molecular mechanisms with a primary focus on epigenetic effects associated with prenatal and childhood exposure to persistent organic pollutants (DDT and PBDEs). We measured several types of DNA methylation including repetitive element methylation by pyrosequencing (Alu and LINE-1) and site=specific genome-wide methylation using the Illumina 450K BeadChip array. We also characterized the differences in multiple epigenetic marks by host factors like age and sex in children from birth to 12 years of age and assessed relationships of epigenetic modifications in children with hormone levels and pubertal onset.
Project C Specific Aims: 1. To analyze global DNA methylation in newborn children by three different assays. 2. To determine ontogenetic changes in global DNA methylation in blood of children between birth and 12 years. 3. To investigate the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global DNA methylation. 4. To determine whether global methylation is associated with onset of puberty and hormonal changes 5. To examine site-specific methylation in relation to age, sex, exposure to DDT/E and PBDEs and puberty onset. |
1. Developing data pipelines for analysis of 450K methylation. The Illumina 450K methylation BeadChip allows for assessment of methylation levels at >450,000 CpG sites in the epigenome. High dimensional datasets, such as those generated by the 450K BeadChip, require adequate quality control and normalization prior to analysis of biological outcomes. We determined that the normalization methodologies provided by Illumina’s Genome Studio software for 450K assay data were inadequate for reducing technical variability, potentially biasing results. We developed a normalization method called All Sample Mean Normalization (ASMN), to reduce the technical variability encountered in large epidemiologic studies (Yousefi et al 2013). The ASMN procedure performed consistently better than alternative methodologies at reducing batch effects and increasing repeatability among technical replicates. ASMN is now available as an open source Bioconductor software package.
Another important methodological question we addressed using the 450K data from the CHAMACOS cohort is potential confounding in methylation studies by blood composition since methylation levels can differ among white blood cell types. The Houseman adjustment implemented in the Bioconductor package minfi is the most commonly used method for estimation of cell composition in blood specimens assessed by the 450K BeadChip. However, the algorithm is based on the methylation profiles of 6 Swedish men. The immune profiles in young children, especially newborns, are vastly different than those of adults. We estimated white blood cell type percentages by two methods, (1) minfi and (2) direct differential cell count (DCC), at two time points in childhood (birth and 12 years of age). We found that while both minfi and DCC had similar trends in older children, minfi estimates did not correlate well with DCC in samples from newborns (ρ = -0.05 for granulocytes; ρ = -0.03 for lymphocytes), demonstrating that the minfi method may not provide suitable estimates of white blood cell composition for newborns or young children. A manuscript on the estimation of blood cell heterogeneity in children for epigenome-wide studies was published in Environmental and Molecular Mutagenesis (EMM) (Yousefi et al. 2015).
DNA methylation and host factors. We found significant associations of DNA methylation with host factors such as sex and age. Levels of repetitive element DNA methylation were lower in 9-year olds compared to newborns and were higher in boys compared to girls (Figure C1). 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. These findings were published in EMM (Huen et al. 2014). To identify CpG sites differentially methylated by age, we used 450K data assessed in newborns and 12 year olds who had differential cell counts (DCC) assessed. Using the DCC data to control for blood cell composition, we found 499 CpGs associated with aging from birth to 12 years of age (FDR P<0.05). These sites largely decrease in methylation as children aged (89.2%) and are predominantly located in gene bodies. Many of these sites were located in genes that have previously been associated with differences in methylation by age in other studies. We observed that ~3% of CpG sites interrogated by the 450K BeadChip in umbilical cord blood specimens were differentially methylated between girls and boys at birth (FDR P<0.05), after adjusting for cell composition (Figure 5). Of those CpGs, 3,031 were located on autosomes, and 82.9% of those were hypermethylated in girls compared to boys. Beyond individual CpGs, we found 3,604 sex-associated differentially methylated regions (DMRs) where the majority (75.8%) had higher methylation in girls. Using pathway analysis, we found that sex-associated autosomal CpGs were significantly enriched for gene ontology terms related to nervous system development and behavior. Among hits in our study, 35.9% had been previously reported as sex-associated CpG sites in other published studies. Further, for almost all replicated hits, the direction of the association with methylation was concordant with previous studies. Although there was a comprehensive meta-analysis of 76 studies using 27K site-specific methylation data at the time (2014/15), no such study had yet been published using the more comprehensive 450K assay. Ours was the first study to look at differential methylation over regions of CpG sites and adjusting for potential confounding by blood cell composition. These results were published in BMC Genomics (Yousefi et al. 2015).
3. DNA methylation and prenatal exposures to DDT/E and PBDE. We observed a consistent trend of lower Alu and LINE-1 methylation in fetal blood with higher prenatal DDT/E exposure, particularly after adjusting for cell type composition (Figure C2). There was a trend of lower levels of LINE-1 methylation with prenatal PBDE exposures but this relationship did not reach statistical significance. Since mothers were exposed to both PBDEs and DDT/E during pregnancy, we also examined the potential association of co-exposure to these chemicals with levels of Alu and LINE-1 methylation. When we included both classes of chemicals in the same model, we found a significant interaction between sum of PBDEs and o,p’-DDT and p,p’-DDE (p=0.12 and 0.06, respectively) on LINE-1 but not Alu methylation in fetal cord blood. Similar but non-significant interaction was seen for the sum of PBDE congeners with p,p’-DDT. These data suggest that the significant association of prenatal PBDE exposure with LINE-1 methylation in cord blood was only observed after considering exposure to both classes of compounds (PBDEs and DDT/E). Our data demonstrate that prenatal exposure to persistent organic pollutants (POPs) may be linked to hypomethylation in fetal blood and that accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies. These results, suggestive of interactions of different chemicals on epigenetic marks, were published in EMM (Huen et al. 2014).We also conducted analysis of 450K methylation in relation to prenatal PBDE and DDT/E exposure. We did not identify any differentially methylated positions (DMPs) with these exposures. Building upon the methodologies used for the analyses of prenatal DDT/E and PBDE exposure on cord blood DNA methylation, we also examined association of prenatal phthalate exposure with site-specific DNA methylation in cord blood. These data were recently published in EMM (Solomon et al. 2017).
Figure C2. 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
We also conducted analysis of 450K methylation in relation to prenatal PBDE and DDT/E exposure. We did not identify any differentially methylated positions (DMPs) with these exposures. Building upon the methodologies used for the analyses of prenatal DDT/E and PBDE exposure on cord blood DNA methylation, we also examined association of prenatal phthalate exposure with site-specific DNA methylation in cord blood. These data were recently published in EMM (Solomon et al. 2017).
Figure C3. Distribution of hormone levels in 12 year old CHAMACOS boys. Reference levels of LH range from 0.3-6.0 mIU/mL in prepubertal boys and 1.6-12 mIU/mL in adult males. FSH reference levels range from 0.5-10.5 mIU/mL in 14 year old boys. Reference levels of testosterone range from 7-800 ng/dL at age 12 and from 100-1200 at age 15-18 years.
DNA methylation and puberty and hormones. This Center grant includes the follow-up of boys only. However, we received an NIEHS grant (ES017054) to assess pubertal onset in the girls in the CHAMACOS cohort. Although we found no significant relationship between pubertal onset as determined by Tanner staging (testicular volume or pubic hair) and either LINE-1 or Alu measures in boys, we observed a non-significantly higher odds (β (95%CI) = 1.23 (0.88, 1.72)) of girls entering puberty by age 9 years (Tanner stage > B1) with higher LINE-1 methylation (but not Alu methylation) in cord blood. Similarly, we also found a suggestive trend (p=0.15) of an increased odds of having entered puberty by 9 years (Tanner stage > B1) in girls with higher Alu methylation in 9-year old blood.
We also measured concentrations of luteinizing hormone (LH), testosterone (T), and follicle stimulating hormone (FSH) in first-morning serum samples collected from the boys at 12 years (Figure C3) that demonstrate that hormone levels in CHAM1 boys were comparable to normal reference ranges. We found a significant positive relationship between Alu methylation in cord blood and levels of T in boys 12 years later (β (95%CI) = 0.80 (0.13, 1.49)) (see Figure C4). In addition, we observed a significant positive relationship between LINE-1 and ln LH (p=0.03). These data were published in Pediatric Research (Huen et al. 2016).
Figure C4. Cord blood Alu methylation and Testosterone levels in 12 y.o. boys
5. Site-specific methylation. We did not find significant associations between site-specific methylation (cord blood and 9 yrs.) 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 5 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.
Figure 5. Manhattan plot for association between child sex (females) and DNA methylation at all 450K CpGs, adjusting for batch and cell composition by differential cell count (DCC). Associations where methylation was higher for girls relative to boys are plotted above the x-axis, while those with decreased methylation are plotted below. CpGs meeting FDR multiple testing threshold of (P<0.05) shown in red
-
- Others findings. We recently collaborated with Elior Rahmani and Dr. Eran Halperin (UCLA) to show that population structure (ancestry information) can be inferred from genome-wide methylation data such as that provided by the 450K BeadChip platform. A manuscript describing these data and the EPISTRUCTURE method used to infer ancestry from 450K data have been published in Epigenetics and Chromatin (Rahmani et al. 2017).
Building upon our work developed for this project, we have also been active participants in the Pregnancy and Childhood Consortium (PACE), an international consortium of birth cohorts with 450K BeadChip data. It provides a unique opportunity to join forces with multiple cohorts to investigate the relationships of cord blood DNA methylation with various exposures using much larger sample sizes. Thus far, we have been active in several projects. We have published papers on 450K cord blood methylation with smoking and maternal BMI (Joubert et al. 2016, Sharp et al 2017) and have also published a PACE cohort concept paper (Felix et al 2017) as well. Currently, we are spearheading efforts to determine sex differences in DNA methylation among PACE cohorts and a manuscript will be submitted in 2018 (Solomon et al. ). We are also involved in several ongoing projects looking at cord blood DNA methylation in relation to birthweight (Küpers et al), gestational weight gain, and child BMI at various ages.
- The Biorepository Core
Over the past 18 years, we have collected over 330,000 environmental and biologic specimens. These specimens were collected and stored to maximize future utility. We developed standard operating procedures with quality controls for each specimen type, and developed tracking, processing and storage systems. We have improved multiple facets of the Biorepository, expanding the number of -80 freezers, migrating our databases to SQL servers, and upgrading our temperature monitoring system to ensure the safety of our samples and data. These samples have provided resources for additional grants and research, including an NIEHS R21 (R21ES021833) examining exposures and health effects of organophosphate flame retardants and current proposed analyses under consideration by the NIEHS-funded ECHO consortium, of which CERCH is a participating cohort
(https://www.niehs.nih.gov/research/programs/environmental/index.cfm).
- Community Outreach and Translation Core (COTC)
COTC Specific Aims: 1. To disseminate Center research findings to study participants, the Salinas Valley community, and other stakeholders. 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. 3. To build the capacity of Salinas Valley youth to promote healthy environmental policies in their community. 4. To educate policy makers at the local, state, and national levels about Center research findings and children’s environmental health priorities. |
The COTC Core enables Center scientists and community partners to communicate study findings in a culturally-appropriate manner, to raise awareness of children’s environmental health within and beyond the Salinas Valley, and to support policies that improve the health of low-income Latino residents locally in Monterey County and throughout the state and nation. Our center has increasingly prioritized training local residents to become researchers in their own community and building local capacity for continued efforts. We have achieved all major objectives of the Center and community outreach activities have attracted outside funding which continue to support community outreach and education and additional research projects.
1. Outreach to participants: Through the project period we hold regular participant forums to report results to CHAMACOS participants, our most recent forum took place in June 2017. These events are well attended, usually about 300 people, including parent and child participants and family members. At forum we provide refreshments, presentations on study findings, childcare, activities for children, and opportunities for Youth Community Council (see below) members to participate in the event.
2. Electronic Hard Copy Newsletter: We regularly email a CERCH Enewsletter to roughly 1000 Salinas Valley area residents. The newsletter described research findings, includes announcements for upcoming study activities, such as planned milestones such as the 16 year visit with CHAMACOS participants, new funding, such as our participation in the NIEHS Environmental Influences on Child Health Outcomes Program, and also media and other attention to the CHAMACOS study. For example, we were featured on an episode of Mark Bittman’s op-ed video in the New York Times, titled “A Watchful Eye on Farm Families’ Health”. This piece discussed the complexities of pesticide use, including potential negative health affects related to exposures during different life stages. We also mail a hardcopy newsletter before each community advisory board meeting (see below). The newsletter (https://apple.news/Axwel2jLrRV2tNcXt6J0o3g) is sent to all participants and community stakeholders and also describes research findings, includes announcements for upcoming study activities, and also includes public health messages addressing environmental health, parenting and related family issues, etc.
3. 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. Specifically:
4. Outreach to farmworkers: The greatest educational need we have identified in our community outreach work is accessible, quality training for farmworkers about the hazards of pesticide exposure and means to prevent exposure. To address this need, we have conducted hundreds of trainings addressing pesticide and other environmental exposures and exposure prevention, along with presenting results of the CHAMACOS studies. Please see the attached list of close to 500 presentations in the Salinas Valley addressing a wide range of environmental health topics. Additionally, we partnered with the Clinica de Salud del Valle de Salinas (our main community partner) and California Department of Education, Migrant Education Program worked to obtain an EPA Environmental Justice Small Grant. This grant, titled “Proyecto La Semilla: Pesticide Safety Leadership Training for Farmworker Parents”, allowed our team’s primary health educator to train parent leaders in eight agricultural counties throughout California on how to educate other parents on pesticide safety using strategies and teaching materials developed and tested through our Center (i.e. a train-the-trainer program). We were able to successfully meet the project goals, educating approximately close to 300 farmworkers on Worker Protection Standards (WPS), providing them with public speaking trainings and materials to lead their own subsequent trainings with other members of the community. Many participants have have in turn educated members of their community. Based on this pilot project, we have obtained follow-up funding (FY 2018) from the California Department of Education Migrant Education Program (MEP) to expand the train the trainer program to all regions served by MEP. We are currently conducting this project. In addition to the formal WPS training, we conduct extensive community outreach and education addressing environmental health and pesticide exposure-prevention and report findings of the CHAMACOS study to farmworker audiences statewide.
5. Outreach to social service organizations: Center staff have continued 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. Please see our extensive list of presentations and topics for more information.
6. Outreach to growers and the agricultural industry and regulators: We continue to maintain close ties with agriculture regulators and producers. We disseminate recent research findings to members of our CHAMACOS Community Advisory Board (CAB) and a second, smaller Agriculture Council. Members include farmworkers, the Monterey County Agricultural Commissioner, the California Department of Pesticide Regulation, Grower Shipper Association, California Strawberry Commission, Jacob’s Farms, Nunes Company, and the Monterey County Farm Bureau. We share all research findings with the CAB before publication for input and review, and brief local stakeholders on press and other coverage. Our objective is to ensure that all stakeholders have consistent and equal access to findings produce by the CHAMACOS partnership. Finally, Dr. Asa Bradman was appointed by Agriculture Secretary Tom Vilsack to the USDA National Organic Standards Board. In this capacity he has extensive contact with California organic and conventional farmers, including reporting of findings from the CHAMACOS study.
7. Outreach to childcare providers: We continue to provide education and outreach addressing environmental quality in child-care settings in the Salinas Valley and throughout California. Please see the attached list of presentations for events focused on child care. We also obtained several grants from the California Department of Pesticide Regulation (DPR) to develop training resources for child care providers on integrated pesticide management (IPM) and green cleaning and sanitizing (see https://cerch.berkeley.edu/resources/educational-materials). We also obtained funding to develop a training course for licensed pest management professionals serving child care facilities and schools in California. This course provides required continuing education units for pest management professionals and involved close collaboration with child care professionals, the UC Cooperative Extension IPM program, DPR, and the Pest Control Operators of California, the lead trade organization for pest management professionals. To date, about 1200 pest management professionals have completed the course. The on-line version will be operated permanently by the University of California (UC) IPM program and will become a long-term resource for California pest management professionals. Dr. Bradman also participates on the Science Advisory Board for the Children’s Environmental Health Network Eco Healthy Child Care (EHCC) program and has provided extensive review of their educational materials.
Over the project period, we held approximately 500 meetings with a wide range of groups, most of them in the Salinas Valley, to discuss recent Center findings and other environmental health issues. Center staff also attended many 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 approximately 27,000 community members, including roughly 6,300 children. See COTC tracking information attached. (Note, information on the number of participants attending roughly 65 events, mainly between 2010 and 2011 was lost due to a database error. Thus the total number of people reached was higher. If the average attendance from all other recorded events was added for these missing values, the total number of people reached by CHAMACOS outreach efforts would rise by almost 3,200 people, for a total of approximately 30,000).
-
- Dissemination to the scientific community: To date, approximately 150 scientific articles related to the CHAMACOS study have been published. See bibliography for a list of relevant publications and presentations to scientific and other audiences. As a result of knowledge gained from this Center, Drs. Eskenazi, Harley, Bradman, Holland, and Deardorff have also provided consultations across the world addressing methods to conduct birth cohort studies, pesticide research, and exposure prevention education, including Chile, Israel, Bangladesh, South Africa, Costa Rica, Spain, Ecuador, Vietnam, Nepal, and New Zealand. CHAMACOS senior investigators are also deeply involved in planning and workgroups for the NIEHS ECHO study.
9. Website: We developed an online resource center (ORC) where specific audience groups can access information on environmental health hazards with resources and tips on ways to 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. Our website was migrated to https://cerch.berkeley.edu/ to increase program security. In the last year, we had 10,470 unique users, 14,520 website visits, and 26,740 page views.
10. To build the capacity of Salinas Valley youth: The goal of the Youth Community Council (YCC) is to build youth capacity in environmental health and to engage youth in promoting healthy environmental policies in Salinas. Harnessing a youth participatory action research (YPAR) model also helps researchers understand and incorporate local needs, perspectives and experiential expertise into study processes, thereby improving the likelihood that research aligns with community priorities, is conducted in an appropriate and effective manner, and that findings are disseminated in a form most likely to reach, and be understood by, the most people possible. During the project period, we convened the YCC and implemented several local projects prioritized by the youth:
Photovoice Project: YCC youth were given camera’s and took pictures of environmental health concerns in their neighborhoods. Images from this photovoice project were exhibited at the Monterey County Health Department.
Walkability Project: The Monterey County Health Department funded a survey by CHAMACOS YCC youth to assess walkability (ease of walking, accessibility, safety, etc) of Salinas neighborhoods. Findings from the survey were presented to the health department.
The Healthy Retail Project, also funded by the Monterey County Department of Public Health: In 2014, the local health department selected the CHAMACOS YCC from among other local applicants to administer a Healthy Retail Project in Salinas in summer 2015 (currently underway). The Healthy Retail Project is a small intervention project intended to encourage local corner store owners to make healthy changes to their stores. The project consisted of enrolling owners of local corner stores, conducting a baseline interview with owners regarding their thoughts on the role of food stores in promoting public health, completing an observation checklist about the baseline health quality of the store (e.g. presence, quality, and variety of fresh produce and whole grain products; presence of tobacco and alcohol advertising, etc), and completing brief surveys with approximately 50 customers of each corner store regarding their current shopping habits, items they’d like to see at the store, and their support of potential healthy changes to the store. On the basis of baseline and customer information, we provided a fact sheet for each store with information on its customer base and store-specific suggestions for achievable, healthy changes that are likely to appeal to the customer base. For owners who were willing to attempt changes, we offered the voluntary assistance of YCC members in procuring health promotion materials from the health department, rearranging store displays to highlight healthier products, etc. YCC members will summarized all data collected in a final report to the Monterey County Department of Public Health detailing the baseline health quality of local corner stores and attitudes of owners towards health promotion, the degree to which local residents who shop at these stores feel they have access to healthy foods they need or want, and the willingness of store owners to make healthy changes, and/or the supports they required to make these changes.
Hermosa Study: These early YCC projects evolved in the Hermosa study funded by the California Breast Cancer Research Program. The HERMOSA project (Harley, PI, California Breast Cancer Research Program) was initiated in 2012 to study exposure of Latina youth to endocrine disrupting chemicals (EDC) used in cosmetics and personal care products. Over the summer of 2013, youth worked with researchers to conduct an intervention study to investigate whether using low-chemical cosmetics could lower EDCs in these girls. The study involved youth in each phase of the research project from study design, to data collection, to disseminating results. Findings indicated significant reductions in teen girl’s exposures to potentially EDCs. In addition, nearly 100% of HERMOSA youth researchers went on to enroll in college, a much greater portion than in Salina’s general high school population. Participating you interacted extensively with local media and state legislators and co-authored a widely-cited scientific publication (Harley et al. 2016). In 2015, we again received a 3 year grant (COSECHA study) from California Breast Cancer Research to execute a youth participatory action research of Latina teen’s exposures to potentially hormone disrupting or carcinogenic pesticides in the Salinas Valley.
11. Educate policy makers at the local, state, and national levels about Center research: As described earlier, we maintain an active Community Advisory Board (CAB) that includes local and state regulatory officials (Monterey County Health Officer and Agricultural Commissioner and a Toxicologist with the California Department of Pesticide Regulation). These officials receive all CHAMACOS research findings and publications and participate in CAB meetings.
Drs. Eskenazi and Bradman presented CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) findings to the California Department of Pesticide Regulation in early 2015, which subsequently classified chlorpyrifos as a restricted material on July 1, 2015, in part based on CHAMACOS study findings. CHAMACOS researchers also presented their findings to the California Senate Committee on Environmental Quality which is reviewed proposed state regulations governing pesticide use near schools and child care facilities (http://www.cdpr.ca.gov/docs/pressrls/2016/160929.htm), and is advising the Monterey County Agricultural Commissioner on a pilot program requiring notification of schools about nearby pesticide use. These proposals were finalized in a new California rule limiting pesticide use near schools and childcare (http://www.cdpr.ca.gov/docs/pressrls/2017/110717.htm). CHAMACOS studies were also cited by the U.S. EPA in their evaluation of chlorpyrifos and the impacts of other organophosphate pesticides.
Our pesticide research was shared at the national level when our Center provided 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 were adopted in 2015 to make the regulation more effective (https://www.epa.gov/pesticide-worker-safety/agricultural-worker-protection-standard-wps). We submitted comments to the 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.
Additionally, in 2014, the State of California adopted new furniture flammability rules that allowed non-chemical methods to achieve fire safety. This decision was in part based on CERCH findings of flame retardant exposure and health impacts on CHAMACOS participants.
In Spring 2015, three YCC representatives and research staff visited the capital to educate policymakers about the importance of environmental research and about the HERMOSA Project, how it was conducted, and what the study found. The group met with the staff of four state legislators and of the governor of California. The YCC representatives described our work at the Center and the HERMOSA Study and expressed their concern about chemicals in personal care products. Specifically, they met with Assemblymember Lorena Gonzalez as well as with staffers from the offices of Assembly members Tony Thurmond, David Chiu, Lorena Gonzalez and Senator Mark Leno. They also met with two staffers from the Governor's office (Martha Guzman-Aceves, Deputy Legislative Secretary, Environment and Donna Campbell, Deputy Legislative Secretary, Health and Human Services).
12. Significance
The COTC core of our Center has focused on communicating study findings in a culturally-appropriate manner, raising awareness of children’s environmental health within and beyond the Salinas Valley, and supporting policies to improve the health of low-income Latino residents locally in Monterey County and throughout the state and nation. These core foci are well-aligned with EPA’s commitment to mitigate health risks which are environmental in origin, many of which disproportionately affect poor and socially marginalized communities.
As CHAMACOS children have matured to teens over the course of the current Center funding cycle, our COTC has increasing focused on youth both as recipients of environmental education and as agents of environmental justice. The foremost achievement of our COTC under this phase of Center funding has been to establish a dynamic Youth Community Council (YCC) which we believe embodies EPA’s goal of empowering communities to better characterize environmental health problems and create solutions. Our initial focus on educating high-school age Salinas youth - many from immigrant farmworker families - to recognize and understand locally-relevant environmental health problems took on new form and new energy when we decided to train these youth in environmental epidemiology and empower them to investigate issues of concern and interest to them. The youth researcher model we have developed has proven a magnet for additional project funding. In the past year, supported by both Center/EPA and outside funding, YCC researchers have created teen-friendly resources to help local youth minimize exposure to endocrine-disrupting chemicals in personal care products (based on their successful implementation of an intervention study with this aim in 2013), have designed and begun to implement a Healthy Retail intervention project whose aim is to encourage owners of local corner stores to adopt healthy changes, and have helped attract funding to conduct an intensive teen pesticide exposure study in 2016 which will use silicone bracelets as a novel exposure marker. The opportunity to work hand-in-hand with Center scientists and research staff through each stage of various environmental health research studies has armed YCC youth with a set of applied research skills which few students gain even at college level, and has prompted many to consider or actually pursue science majors in college. Opportunities for community-wide environmental health education have also arisen organically from YCC work. These have included TV, radio, and newspaper coverage of YCC research activities, as well as chances for YCC youth to enhance science education and pique the interest of fellow students by presenting their work in high school and middle school science classes.
In short, through fruitful alliances and continual realignment of our work to the needs and interests of the community we serve, our COTC has allowed us to fulfill our initial commitment to give back more to the community that we take from it, and has helped us establish ourselves as a reliable source of environmental health information that is relevant and accessible to immigrant farmworker communities as well as the broader population.
Journal Articles on this Report : 15 Displayed | Download in RIS Format
Other subproject views: | All 77 publications | 38 publications in selected types | All 38 journal articles |
---|---|---|---|
Other center views: | All 694 publications | 167 publications in selected types | All 166 journal articles |
Type | Citation | ||
---|---|---|---|
|
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) R834513 (Final) R834513C001 (2012) R834513C002 (Final) R834513C003 (Final) |
Exit |
|
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) R834513 (2014) R834513 (Final) R834513C001 (2012) R834513C001 (2014) R834513C002 (Final) R834513C003 (Final) R826709 (2002) R831710 (Final) |
Exit Exit Exit |
|
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) R834513 (2014) R834513C001 (2012) R834513C001 (2014) R834513C002 (Final) R834513C003 (Final) R826709 (2002) |
Exit Exit Exit |
|
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) R834513 (2012) R834513 (2013) R834513 (2014) R834513 (Final) R834513C001 (2012) R834513C002 (2012) R834513C002 (2013) R834513C002 (Final) R834513C003 (Final) |
Exit Exit Exit |
|
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) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2014) R834513C001 (2015) R834513C001 (2016) R834513C002 (Final) R834513C003 (Final) |
Exit Exit |
|
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) R834513 (Final) R834513C002 (2013) R834513C002 (Final) R834513C003 (Final) |
Exit Exit Exit |
|
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) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R834513C003 (2010) R834513C003 (2011) R834513C003 (Final) R831710 (Final) R832734 (Final) |
Exit Exit Exit |
|
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) R834513 (2012) R834513 (2013) R834513 (Final) R834513C002 (2011) R834513C002 (2012) R834513C002 (2013) R834513C003 (Final) |
|
|
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) R834513C002 (2014) R834513C003 (Final) |
Exit Exit Exit |
|
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) R834513 (2016) R834513C002 (2014) R834513C002 (2015) R834513C002 (2016) R834513C003 (Final) |
|
|
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) R834513 (2011) R834513 (Final) R834513C002 (2010) R834513C002 (2011) R834513C003 (Final) R831710 (Final) |
|
|
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) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C001 (2012) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R834513C003 (2012) R834513C003 (Final) R831710 (Final) |
Exit Exit Exit |
|
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 (2016) R834513 (Final) R834513C001 (2016) R834513C003 (Final) |
Exit Exit Exit |
|
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) R834513C003 (Final) |
Exit Exit Exit |
|
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) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2014) R834513C002 (2014) R834513C002 (Final) R834513C003 (Final) |
|
Supplemental Keywords:
RFA, Scientific Discipline, Health, INTERNATIONAL COOPERATION, Health Risk Assessment, Biochemistry, Children's Health, Environmental Policy, Biology, farmworkers, pesticide exposure, flame retardants, PBDE, children's vulnerablity, neurochemical effects, harmful environmental agents, biological markers, agricultural communityProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834513 Center for Integrative Research on Childhood Leukemia and the Environment - 2015 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- 2016 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- 2010 Progress Report
- Original Abstract
38 journal articles for this subproject
Main Center: R834513
694 publications for this center
166 journal articles for this center