Non-chemical Exposures Research Articles

Epigenetic Responses to Nonchemical Stressors: Potential Molecular Links to Perinatal Health Outcomes.

We summarize the recent literature investigating exposure to four nonchemical stressors (financial stress, racism, psychosocial stress, and trauma) and DNA methylation, miRNA expression, and mRNA expression. We also highlight the relationships between these epigenetic changes and six critical perinatal outcomes (preterm birth, low birth weight, preeclampsia, gestational diabetes, childhood allergic disease, and childhood neurocognition). Multiple studies have found financial stress, psychosocial stress, and trauma to be associated with DNA methylation and/or miRNA and mRNA expression. Fewer studies have investigated the effects of racism. The majority of studies assessed epigenetic or genomic changes in maternal blood, cord blood, or placenta. Several studies included multi-OMIC assessments in which DNA methylation and/or miRNA expression were associated with gene expression. There is strong evidence for the role of epigenetics in driving the health outcomes considered. A total of 22 biomarkers, including numerous HPA axis genes, were identified to be epigenetically altered by both stressors and outcomes. Epigenetic changes related to inflammation, the immune and endocrine systems, and cell growth and survival were highlighted across numerous studies. Maternal exposure to nonchemical stressors is associated with epigenetic and/or genomic changes in a tissue-specific manner among inflammatory, immune, endocrine, and cell growth-related pathways, which may act as mediating pathways to perinatal health outcomes. Future research can test the mediating role of the specific biomarkers identified as linked with both stressors and outcomes. Understanding underlying epigenetic mechanisms altered by nonchemical stressors can provide a better understanding of how chemical and nonchemical exposures interact.

Making the invisible visible: Using a qualitative system dynamics model to map disparities in cumulative environmental stressors and children's neurodevelopment

BackgroundThe combined effects of multiple environmental toxicants and social stressor exposures are widely recognized as important public health problems, likely contributing to health inequities. However, US policy makers at state and federal levels typically focus on one stressor exposure at a time and have failed to develop comprehensive strategies to reduce multiple co-occurring exposures, mitigate cumulative risks and prevent harm. This research aimed to move from considering disparate environmental stressors in isolation to mapping the links between environmental, economic, social and health outcomes as a dynamic complex system using children's exposure to neurodevelopmental toxicants as an illustrative example. Such a model can be used to support a broad range of child developmental and environmental health policy stakeholders in improving their understanding of cumulative effects of multiple chemical, physical, biological and social environmental stressors as a complex system through a collaborative learning process. MethodsWe used system dynamics (SD) group model building to develop a qualitative causal theory linking multiple interacting streams of social stressors and environmental neurotoxicants impacting children's neurodevelopment. A 2 1/2-day interactive system dynamics workshop involving experts across multiple disciplines was convened to develop the model followed by qualitative survey on system insights. ResultsThe SD causal map covered seven interconnected themes: environmental exposures, social environment, health status, education, employment, housing and advocacy. Potential high leverage intervention points for reducing disparities in children's cumulative neurotoxicant exposures and effects were identified. Workshop participants developed deeper level of understanding about the complexity of cumulative environmental health risks, increased their agreement about underlying causes, and enhanced their capabilities for integrating diverse forms of knowledge about the complex multi-level problem of cumulative chemical and non-chemical exposures. ConclusionGroup model building using SD can lead to important insights to into the sociological, policy, and institutional mechanisms through which disparities in cumulative impacts are transmitted, resisted, and understood.

Powering Research through Innovative Methods for Mixtures in Epidemiology (PRIME) Program: Novel and Expanded Statistical Methods.

Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health.

Influence of perceived stress on prenatal depression in Surinamese women enrolled in the CCREOH study

BackgroundPrenatal depression may have adverse health effects on mothers and their offspring. Perceived stress is an important risk factor for depression during pregnancy. Studies have shown that both perceived stress and depression may negatively influence birth outcomes. While 20% of pregnancies in Suriname, a middle-income Caribbean country located in northern South America, results in adverse birth outcomes, data on prenatal depression and its risk factors are lacking. This study aimed to assess the influence of perceived stress on depression during pregnancy in Surinamese women.MethodsSurvey data were used from 1143 pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health-MeKiTamara prospective cohort study that addresses the impact of chemical and non-chemical environmental exposures in mother/child dyads in Suriname. The Edinburgh Depression Scale and Cohen Perceived Stress Scale were used to screen for probable depression (cut-off ≥ 12) and high stress (cut-off ≥ 20), respectively. The association between perceived stress and depression was examined using bivariate and multiple logistic regression analyses, adjusted for social support (including resilience) and maternal demographics.ResultsThe prevalence of high perceived stress during the first two trimesters and the third trimester were 27.2% and 24.7% respectively. 22.4% of the participants had probable depression during first or second trimester and 17.6% during the third trimester. Women experiencing high stress levels during the first two trimesters had 1.92 increased odds (95% CI 1.18–3.11, p = 0.008) of having probable depression during the third trimester of pregnancy than those with low stress levels. Pregnant women with low individual resilience during early pregnancy (52.1%) had 1.65 (95% CI 1.03–2.63, p = 0.038) increased odds of having probable depression during later stages of pregnancy compared to those with high individual resilience. Low educational level (p = 0.004) and age of the mother (20–34 years) (p = 0.023) were significantly associated with probable depression during the third trimester.ConclusionsEarly detection and management of stress and depression during pregnancy are important. Health education programs, targeting the reduction of stress during pregnancy, may help to reduce depression and its potential adverse health effects on the mother and child.

Joint effects of prenatal exposure to per- and poly-fluoroalkyl substances and psychosocial stressors on corticotropin-releasing hormone during pregnancy

BackgroundPrenatal exposure to per- and poly-fluoroalkyl substances (PFAS) and psychosocial stressors has been associated with adverse pregnancy outcomes, including preterm birth. Previous studies have suggested that joint exposure to environmental chemical and social stressors may be contributing to disparities observed in preterm birth. Elevated corticotropin-releasing hormone (CRH) during mid-gestation may represent one biologic mechanism linking chemical and nonchemical stress exposures to preterm birth.MethodsUsing data from a prospective birth cohort (N = 497), we examined the cross-sectional associations between five individual PFAS (ng/mL; PFNA, PFOA, PFOS, PFHxS, and Me-PFOSA-AcOH) and CRH (pg/mL) using linear regression. PFAS and CRH were measured during the second trimester in serum and plasma, respectively. Coefficients were standardized to reflect change in CRH associated with an interquartile range (IQR) increase in natural log-transformed PFAS. We additionally examined if the relationship between PFAS and CRH was modified by psychosocial stress using stratified models. Self-reported depression, stressful life events, perceived stress, food insecurity, and financial strain were assessed using validated questionnaires during the second trimester and included as binary indicators of psychosocial stress.ResultsAn IQR increase in PFNA was associated with elevated CRH (β = 5.17, 95% confidence interval [CI] = 1.79, 8.55). Increased concentrations of PFOA were also moderately associated with CRH (β = 3.62, 95% CI = −0.42, 7.66). The relationship between PFNA and CRH was stronger among women who experienced stressful life events, depression, food insecurity, and financial strain compared to women who did not experience these stressors.ConclusionsThis cross-sectional study is the first to examine the relationship between PFAS exposure and CRH levels in mid-gestation. We found that these associations were stronger among women who experienced stress, which aligns with previous findings that chemical and nonchemical stressor exposures can have joint effects on health outcomes.

An exposomic approach with 138 chemical and non-chemical exposures to predict 32 biomarkers of male reproductive damages: A case study of college students in Chongqing, China

Male reproductive damage in the general population comprises different disorders in various biomarkers, which could be respectively caused by a number of exposure factors. However, researchers considering the environmental/behavioral/psychological exposures together to evaluate their contribution to male reproductive damage are still lacking. The present study investigated the comprehensive association between 138 environmental/behavioral/psychological exposures and 32 male reproductive biomarkers in 796 young Chinese men using graph-guided fused lasso (GFLASSO) and hierarchical clustering methods. All biomarkers were found to be associated with various exposures. A combination of these exposures not only predicted the levels of single biomarkers in another test dataset, but also identified the comprehensive reproductive features by clustering the men into five subgroups with distinct damages representing disrupted spermatogenesis with abnormal sperm morphology, low sperm motility with DNA fragmentation, chromatin immaturity, aberrant endocrine, or DNA strand breakage. The findings can be used to suggest a novel way to identify the males with a high risk of reproductive damage and develop personalized preventive strategies.

Persistent organic pollutants and couple fecundability: a systematic review.

Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research. We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants' prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP. Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.

Making the Invisible Visible: Intervening on cumulative environmental neurodevelopmental risks using a system dynamics approach

Background: The combined effects of multiple environmental toxicants and social stressor exposures are widely recognized as important public health problems, likely contributing to health inequities. However cumulative environmental health risk and impacts have received little attention by US policy makers at state and federal levels to develop comprehensive strategies to reduce these exposures, mitigate cumulative risks and prevent harm. An area for which the inherent limitations of current approaches to cumulative environmental health risk are well illustrated is children’s neurodevelopment which exhibits dynamic complexity, intergenerational effects and interdependent and causally linked nature of multiple factors. Systems science methods enable investigators to examine the dynamic relationships of variables at multiple levels of analysis simultaneously, while also studying the impact of the non-linear behavior of the system as a whole over time. Thus we contend that a systems approach, specifically system dynamics, may be better suited for devising policy solutions to address cumulative effects of multiple chemical, physical, biological and social environmental stressors. Methods: We convened a 2 1/2-day system dynamics workshop involving experts across multiple disciplines to formally describe the multiple interacting streams of social stressors and environmental neurotoxicants impacting children’s neurodevelopment through the use of qualitative system maps and formal system dynamics simulation models. Results: An initial system dynamics causal map was developed, incorporating feedback mechanisms relevant to diverse disciplines. Potential high leverage intervention points for reducing disparities in children’s cumulative neurotoxicant exposures and effects were identified. Workshop participants developed deeper level of understanding about the complexity of cumulative environmental health risks, increased their agreement about underlying causes, and enhanced their capabilities for integrating diverse forms of knowledge about the complex multi-level problem of cumulative chemical and nonchemical exposures. Conclusion: We conclude that this approach successfully enabled a multidisciplinary group to explore relationships in a complex dynamic system.

A Cumulative Risk Perspective for Occupational Health and Safety (OHS) Professionals.

Cumulative risk assessment (CRA) addresses the combined risk associated with chemical and non-chemical exposures. Although CRA approaches are utilized in environmental and ecological contexts, they are rarely applied in workplaces. In this perspectives article, we strive to raise awareness among occupational health and safety (OHS) professionals and foster the greater adoption of a CRA perspective in practice. Specifically, we provide an overview of CRA literature as well as preliminary guidance on when to consider a CRA approach in occupational settings and how to establish reasonable boundaries. Examples of possible workplace co-exposures and voluntary risk management actions are discussed. We also highlight important implications for workplace CRA research and practice. In particular, future needs include simple tools for identifying combinations of chemical and non-chemical exposures, uniform risk management guidelines, and risk communication materials. Further development of practical CRA methods and tools are essential to meet the needs of complex and changing work environments.

Environmental mixtures and children's health: identifying appropriate statistical approaches.

Biomonitoring studies have shown that children are constantly exposed to complex patterns of chemical and nonchemical exposures. Here, we briefly summarize the rationale for studying multiple exposures, also called mixture, in relation to child health and key statistical approaches that can be used. We discuss advantages over traditional methods, limitations and appropriateness of the context. New approaches allow pediatric researchers to answer increasingly complex questions related to environmental mixtures. We present methods to identify the most relevant exposures among a high-multitude of variables, via shrinkage and variable selection techniques, and identify the overall mixture effect, via Weighted Quantile Sum and Bayesian Kernel Machine regressions. We then describe novel extensions that handle high-dimensional exposure data and allow identification of critical exposure windows. Recent advances in statistics and machine learning enable researchers to identify important mixture components, estimate joint mixture effects and pinpoint critical windows of exposure. Despite many advantages over single chemical approaches, measurement error and biases may be amplified in mixtures research, requiring careful study planning and design. Future research requires increased collaboration between epidemiologists, statisticians and data scientists, and further integration with causal inference methods.

Joint impact of phthalate exposure and stressful life events in pregnancy on preterm birth

BackgroundUrinary phthalate metabolites and psychosocial stress in pregnancy have each been associated with preterm birth (PTB), but no study has examined the joint impact of these two environmental exposures. We hypothesized that there would be stronger associations between phthalate exposure and PTB in mothers with higher stress in pregnancy compared to mothers with lower stress. MethodsWe addressed this question using data from The Infant Development and the Environment Study (TIDES), a prospective birth cohort conducted at four US sites (N = 783). We examined urinary phthalate metabolite concentrations measured in samples collected from up to three trimesters of pregnancy. Mothers reported their exposure to stressful life events (SLE) in each trimester in a questionnaire administered in the third trimester. PTB was defined as delivery before 37 weeks completed gestation (n = 71, 9.1%). We examined associations between urinary phthalate metabolite concentrations (individual time points and on average) and PTB using logistic regression models adjusted for maternal race, age, pre-pregnancy body mass index, education, specific gravity, and gestational age at sample collection. In addition, we created models stratified by whether or not mothers were exposed to any or no SLE in pregnancy. ResultsSummed di-2-ethylhexyl phthalate (ΣDEHP) metabolites measured in urine samples from the third trimester, but not the first trimester, were associated with an increased odds ratio (OR) of PTB (OR = 1.44, 95% confidence interval [CI] = 1.06, 1.95). In models stratified by SLE, associations between third trimester ΣDEHP concentrations and PTB were significant only for women experiencing one or more SLE during pregnancy (OR for ΣDEHP: 2.09, 95% CI: 1.29, 3.37) but not for women with no SLE during pregnancy (OR for ΣDEHP: 1.04, 95% CI: 0.66, 1.63) (p for interaction = 0.07). ConclusionsWe observed an association between urinary ΣDEHP levels and PTB that was modified by whether a mother was exposed to one or more psychosocial stressors during pregnancy. Additional research to understand the joint impacts of chemical and non-chemical exposures, with an emphasis on timing of exposure, is needed in order to advance the state of the science on how the environment influences pregnancy.

Phthalate exposure and stressful life events in pregnancy have a joint effect on preterm birth

TPS 632: Health effects of flame retardants and plasticizers, Johan Friso Foyer, Floor 1, August 27, 2019, 3:00 PM - 4:30 PM Background: Urinary phthalate metabolites and psychological stress in pregnancy have been individually associated with preterm birth (PTB), but no study has examined the joint effect of these two environmental exposures. We hypothesized that there would be stronger associations between phthalate exposure and PTB in mothers with higher stress in pregnancy compared to mothers with lower stress. Methods: We addressed this question using data from The Infant Development and the Environment Study (TIDES), a prospective birth cohort conducted at four US sites (N=785). Urinary phthalate metabolite concentrations were measured in samples collected in the first and third trimesters of pregnancy. Stressful life events (SLE) during gestation were assessed by a questionnaire administered in the third trimester. PTB was defined as delivery before 37 weeks completed gestation (n=71). We examined associations between urinary phthalate metabolite concentrations at each visit in association with PTB using logistic regression models adjusted for maternal race, age, pre-pregnancy body mass index, specific gravity, and gestational age at sample collection. Results: Summed di-2-ethylhexyl phthalate (ΣDEHP) metabolites measured in urine samples from the third trimester, but not the first trimester, were associated with an increased odds ratio (OR) of PTB (OR=1.38, 95% confidence interval [CI] =1.01, 1.89). In models stratified by SLE, associations between third trimester ΣDEHP concentrations and PTB were significant only for women experiencing 1 or more SLE during pregnancy (OR: 2.05, 95% CI: 1.28, 3.29) but not for women with no SLE during pregnancy (OR: 0.99, 95% CI: 0.63, 1.55); the interaction was marginally significant (p=0.05). Conclusions: We observed an association between urinary ΣDEHP levels and PTB that was modified by psychological stress in pregnancy. Additional research to understand the joint effects of chemical as well as non-chemical exposures is necessary in order to advance the state of the science on how the environment impacts pregnancy.

The Cumulative Risk of Chemical and Nonchemical Exposures on Birth Outcomes in Healthy Women: The Fetal Growth Study.

Metals, stress, and sociodemographics are commonly studied separately for their effects on birth outcomes, yet often jointly contribute to adverse outcomes. This study analyzes two methods for measuring cumulative risk to understand how maternal chemical and nonchemical stressors may contribute to small for gestational age (SGA). SGA was calculated using sex-specific fetal growth curves for infants of pregnant mothers (n = 2562) enrolled in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. The exposures (maternal lead, mercury, cadmium, Cohen’s perceived stress, Edinburgh depression scores, race/ethnicity, income, and education) were grouped into three domains: metals, psychosocial stress, and sociodemographics. In Method 1 we created cumulative risk scores using tertiles. Method 2 employed weighted quantile sum (WQS) regression. For each method, logistic models were built with three exposure domains individually and race/ethnicity, adjusting for age, parity, pregnancy weight gain, and marital status. The adjusted effect of overall cumulative risk with three domains, was also modeled using each method. Sociodemographics was the only exposure associated with SGA in unadjusted models ((odds ratio) OR: 1.35, 95% (confidence interval) CI: 1.08, 1.68). The three cumulative variables in adjusted models were not significant individually, but the overall index was associated with SGA (OR: 1.17, 95% CI: 1.02, 1.35). In the WQS model, only the sociodemographics domain was significantly associated with SGA. Sociodemographics tended to be the strongest risk factor for SGA in both risk score and WQS models.

Epidemiologically-informed cumulative risk hypertension models simulating the impact of changes in metal, organochlorine, and non-chemical exposures in an environmental justice community

Blood pressure is a leading risk factor for cardiovascular disease, influenced by chemical and non-chemical stressors. Exposure reduction strategies can potentially improve public health, but there are analytical challenges in developing quantitative models of health benefits, including the need for detailed multi-stressor exposure models, corresponding health evidence, and methods to simulate changes in exposure and resultant health benefits. These challenges are pronounced in low-income urban communities, where residents are often simultaneously exposed to numerous chemical and non-chemical stressors. For New Bedford (Massachusetts, USA), a low-income community near a Superfund site, we simulated geographically-resolved individual data, and applied previously published structural equation models developed from National Health and Nutrition Examination Survey (NHANES) data. These models simultaneously predict exposures to multiple chemicals (e.g., lead (Pb), cadmium (Cd), and polychlorinated biphenyls (PCBs)) and non-chemical factors (e.g., socioeconomic status), and determine their combined effects on blood pressure. We then modeled counterfactual scenarios reducing exposures and estimated the resulting changes in blood pressure distribution in the community. Results indicated small shifts in mean blood pressure and percentage of normotensive individuals with a reduction of Pb and/or PCB exposure. For example, a reduction in PCB to the lowest 10th percentile exposure in the NHANES resulted in a 2.4 mm Hg shift in systolic blood pressure (SBP), corresponding with 3% fewer individuals with SBP in the Stage 2 hypertension category [SBP ≥140]. Our model also emphasized the importance of the multi-stressor framework by simulating benefits of reductions in smoking rates, given positive associations with Pb and Cd but inverse associations with body mass index and blood pressure. This research demonstrates the ability to jointly consider chemical and non-chemical exposures and their impact on cardiovascular health, using approaches generalizable to other cumulative risk assessment applications.

Methods for Evaluating the Combined Effects of Chemical and Nonchemical Exposures for Cumulative Environmental Health Risk Assessment.

Cumulative risk assessment (CRA) has been proposed as a means of evaluating possible additive and synergistic effects of multiple chemical, physical and social stressors on human health, with the goal of informing policy and decision-making, and protecting public health. Routine application of CRA to environmental regulatory and policy decision making, however, has been limited due to a perceived lack of appropriate quantitative approaches for assessing combined effects of chemical and nonchemical exposures. Seven research projects, which represented a variety of disciplines, including population health science, laboratory science, social sciences, geography, statistics and mathematics, were funded by the US Environmental Protection Agency (EPA) to help address this knowledge gap. We synthesize key insights from these unique studies to determine the implications for CRA practice and priorities for further research. Our analyses of these seven projects demonstrate that the necessary analytical methods to support CRA are available but are ultimately context-dependent. These projects collectively provided advancements for CRA in the areas of community engagement, characterization of exposures to nonchemical stressors, and assessment of health effects associated with joint exposures to chemical and psychosocial stressors.

Applying an Exposome-Wide (ExWAS) Approach to Cancer Research.

Traditional research approaches, including genome-wide association studies (GWAS), epigenome-wide association studies (EWAS) and Gene × Environment (G × E) studies are limited in their ability to handle the multiplicity of chemical and non-chemical toxicants to which people are exposed in the real world, over their life course, their impact on epigenomics and other biological systems, and their relationship to cancer onset, progression, and outcomes. Exposome-wide association study (ExWAS) provides a new approach for conceptualizing the roles and relationships of multiple chemical and non-chemical exposures in the etiology and progression of cancer at key developmental periods, over the life course, and across generations. ExWAS challenges us to consider the influence of both internal and external environment, chemical and non-chemical stressors, risk and protective factors, and spatial and temporal dimensions of exposures in our models of cancer incidence, outcomes, and disparities. Applying an ExWAS approach to cancer and cancer disparities research supports robust computational models and methods that will allow for analysis of the dynamic and complex interactions between genetics, epigenetics, and exposomics factors. In the coming months, we will spatially and temporally align environmental exposures with SCCS participant data from time of enrollment forward to move us closer to identifying complete exposure pathways that lead to cancer. In the future, we hope to link external sources of exposure to biomarkers of exposure, biomarkers of disease, disease phenotypes, and population level disparities.

Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment

BackgroundLead and psychosocial stress disrupt similar but not completely overlapping mechanisms. Exposure during the prenatal period to each of these insults singularly has been found to alter normal neurodevelopment; however, longitudinal associations with stress modifying the effect of lead have not been sufficiently analyzed in epidemiologic studies. ObjectiveTo evaluate prenatal stress as an effect modifier of gestational lead neurotoxicity. MethodsWe used a structural equations modeling approach with a trivariate response to evaluate cognitive, language and motor scores of the Bayley Scales of Infant Development-III in 24month-old children (n=360). Maternal blood lead levels were measured at the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed using a negative life events (NLE) scale derived from the CRYSIS questionnaire. Results3rd trimester lead (mean 3.9±3.0 SDμg/dL) and stress (median=3 NLE) were negatively associated with Bayley III scores. Using the model's results we generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10μg/dL) and observed a dose–response for the developmental scores when lead levels were below 2μg/dL. Each NLE curve had a different shape across increasing lead levels. Higher stress (NLE=6) resulted in lower cognitive scores for both sexes, in lower language scores in girls but not boys. In the absence of stress we saw a negative association with lead for all scores, however for language and motor scores, higher stress seemed to mask this association. ConclusionsOur work examined and confirmed prenatal stress exposure as a modifier of the well-known neurotoxic effects of prenatal lead. It adds to the existing evidence pointing at the importance of studying the co-exposure of chemical and non-chemical exposures, specifically of considering the emotional environment of children at early developmental stages of life.

Epigenome: A Biomarker or Screening Tool to Evaluate Health Impact of Cumulative Exposure to Chemical and Non-Chemical Stressors

Current risk assessment practices and toxicity information are hard to utilize for assessing the health impact of combined or cumulative exposure to multiple chemical and non-chemical stressors encountered in the “real world” environment. Non-chemical stressors such as heat, radiation, noise, humidity, bacterial and viral agents, and social factors, like stress related to violence and socioeconomic position generally cannot be currently incorporated into the risk assessment paradigm. The Science and Decisions report released by the National Research Council (NRC) in 2009 emphasized the need to characterize the effects of multiple stressors, both chemical and non-chemical exposures. One impediment to developing information relating such non-chemical stressors to health effects and incorporating them into cumulative assessment has been the lack of analytical tools to easily and quantitatively monitor the cumulative exposure to combined effects of stressors over the life course.

The Long Term Impact between Chemical and Non-Chemical Stressors and Musculoskeletal Disorders on Iraqi Residents during the Gulf War

Background: Gulf War (GW) yielded high rates of diseases and disorders to all who participated and those near these active warzones. Certain stressors play a direct role in the prevalence of musculoskeletal disorders. Objective: To determine the effects chemical (Ch) and non-chemical (NCh) stressors have on musculoskeletal disorders of those in and near active warzones and to inform primary care physicians about these adverse effects. Methods: A volunteer, validated, self-reporting survey was given to those who accompanied patients of clinics available to all in the Basrah and Messan provinces of Iraq. In order to examine the severity Ch and NCh stressors have on musculoskeletal disorders three zones were partitioned according to their distance from war zone. Also participants answered questions related to environmental exposure and self-rated health assessment. Results: We found a significant (P<0.001) difference between Ch and NCh exposure across the three zones. Specifically, 49% of those in zone 1 displayed one or more musculoskeletal disorders and those in zone 1 also selfreported having the highest prevalence of fair to poor health. There were also significant predictors to three Ch and two NCh exposures on musculoskeletal disorders. In addition, the likelihood the participants will have one or more musculoskeletal disorder doubles with each exposure which expands the description of. Conclusion: The study showed that the Ch and NCh stressors has a significantly impact on the prevalence of musculoskeletal disorder. In addition, this study found significant, previously unreported links between some of these Ch and NCh exposures and musculoskeletal disorders. This study reports the impact of Ch and NCh exposure on musculoskeletal disorders among non-military persons in active warzones.

Engaging Communities in Research on Cumulative Risk and Social Stress-Environment Interactions: Lessons Learned from EPA's STAR Program.

Studies have documented cumulative health effects of chemical and nonchemical exposures, particularly chronic environmental and social stressors. Environmental justice groups have advocated for community participation in research that assesses how these interactions contribute to health disparities experienced by low-income and communities of color. In 2009, the U.S. Environmental Protection Agency issued a request for research applications (RFA), “Understanding the Role of Nonchemical Stressors and Developing Analytic Methods for Cumulative Risk Assessments.” Seven research projects were funded to help address this knowledge gap. Each engaged with communities in different ways. We describe the community engagement approaches of the seven research projects, which ranged from outreach through shared leadership/participatory. We then assess the experiences of these programs with respect to the community engagement goals of the RFA. We present insights from these community engagement efforts, including how the grants helped to build or enhance the capacity of community organizations in addition to contributing to the research projects. Our analysis of project proposals, annual grantee reports, and participant observation of these seven projects suggests guidelines for the development of future funding mechanisms and for conducting community-engaged research on cumulative risk involving environmental and social stressors including: 1) providing for flexibility in the mode of community engagement; 2) addressing conflict between research timing and engagement needs, 3) developing approaches for communicating about the uniquely sensitive issues of nonchemical stressors and social risks; and 4) encouraging the evaluation of community engagement efforts.