Non-chemical Stressors Research Articles

Synergistic interaction between a toxicant and food stress is further exacerbated by temperature

Global biodiversity is declining at an unprecedented rate in response to multiple environmental stressors. Effective biodiversity management requires deeper understanding of the relevant mechanisms behind such ecological impacts. A key challenge is understanding synergistic interactions between multiple stressors and predicting their combined effects. Here we used Daphnia magna to investigate the interaction between a pyrethroid insecticide esfenvalerate and two non-chemical environmental stressors: elevated temperature and food limitation. We hypothesized that the stressors with different modes of action can act synergistically. Our findings showed additive effects of food limitation and elevated temperature (25 °C, null model effect addition (EA)) with model deviation ratio (MDR) ranging from 0.7 to 0.9. In contrast, we observed strong synergistic interactions between esfenvalerate and food limitation at 20 °C, considerably further amplified at 25 °C. Additionally, for all stress combinations, the synergism intensified over time indicating the latent effects of the pesticide. Consequently, multiple stress substantially reduced the lethal concentration of esfenvalerate by a factor of 19 for the LC50 (0.45–0.024 μg/L) and 130 for the LC10 (0.096–0.00074 μg/L). The stress addition model (SAM) predicted increasing synergistic interactions among stressors with increasing total stress.

Assessment of adverse childhood experiences in adolescents from a rural agricultural community: Associations with depressive symptoms and psychosocial problems

The main goal of this study was to determine the prevalence of adverse childhood experiences (ACEs) among Latino adolescents from an agricultural community and to examine how it may impact their neuropsychiatric functioning. This research particularly assessed the association between ACEs and depression, as well as ACEs and psychosocial problems. The study sample consisted of 852 adolescents treated at a rural primary care clinic with a comprehensive ACE screening protocol that assesses for ACEs, depressed mood, and psychosocial functioning during every annual Well-Child Visit. Study results showed that ACEs were relatively common among participants with 64 % endorsing having experienced at least one ACE. Approximately 23 % of participants screened positive for depressed mood and 11 % for psychosocial problems. ACEs were found to have significant associations with both depression symptoms and with psychosocial problems. Males were found to have less depression symptoms than females among subjects with exposure to most ACE types, and older age was associated with lower psychosocial impairment. Study participants live in an agricultural community and are likely exposed to both chemical and non-chemical stressors. The exposure to ACEs and chemical environmental stressors may interact with pathological synergy to alter their biobehavioral development. Further research is needed to understand the “rules” for which stressors at what dose and at what stage of development place youth at greatest risk.

Chemical and non-chemical stressors in a postpartum cohort through wristband and self report data: Links between increased chemical burden, economic, and racial stress

Multiple external stressors are known to have adverse impacts on health and development. Certain groups are more vulnerable and/or more likely to be exposed toenvironmental, psychological, and social stressors simultaneously. Yet, few studies have examined combined exposure to environmental toxicants and psychosocial stress. Here, we integrated environmental chemical exposure data collected using silicone wristbands and self-report social stressor data within the Brain and Early Experience (BEE) perinatal cohort to understand co-exposure to environmental chemicals and social stress. Silicone wristbands were worn for one week by mothers throughout central North Carolina who were 6 months postpartum (n = 97). Exposure to 110 environmental chemicals across eight chemical classes was quantified on silicone wristbands using gas chromatography mass spectrometry. Social stress was evaluated using eight established self-report questionnaires (e.g., Brief Symptom Inventory, Perceived Stress Scale), quantifying experiences such as race-related stress, economic strain, and relationship conflict. Hair cortisol levels were measured as an additional metric of stress. The chemical exposure landscape and associations among chemical exposure, demographic characteristics, and social stress were characterized through individual variable analyses, cluster and data reduction, and compiled scoring approaches to comprehensively evaluate chemical and social stress burdens. We found that chemicals contain co-occurring patterns largely based on chemical class, with phthalates representing the chemical class with highest exposure and polychlorinated biphenyls the lowest. Chemicals showed differential exposure across racial groups, with diethyl phthalate, triphenyl phosphate, and tris(3,5-dimethyl phenyl) phosphate at higher levels in Black participants compared with White participants. Integrating social stressor profiling with chemical exposure data identified one particularly vulnerable subset of participants in which high chemical exposure burden coincided with high experiences of racism and economic stress. These findings demonstrate co-occurring chemical and social stress, warranting further investigation to better understand how these combined stressors may contribute to disparities in maternal and child health.

Depleted Housing Elicits Cardiopulmonary Dysfunction After a Single Flaming Eucalyptus Wildfire Smoke Exposure in a Sex-Specific Manner in ApoE Knockout Mice

Although it is well established that wildfire smoke exposure can increase cardiovascular morbidity and mortality, the combined effects of non-chemical stressors and wildfire smoke remains understudied. Housing is a non-chemical stressor that is a major determinant of cardiovascular health, however, disparities in neighborhood and social status have exacerbated the cardiovascular health gaps within the United States. Further, pre-existing cardiovascular morbidities, such as atherosclerosis, can worsen the response to wildfire smoke exposures. This represents a potentially hazardous interaction between inadequate housing and stress, cardiovascular morbidities, and worsened responses to wildfire smoke exposures. The purpose of this study was to examine the effects of enriched (EH) versus depleted (DH) housing on pulmonary and cardiovascular responses to a single flaming eucalyptus wildfire smoke (WS) exposure in male and female apolipoprotein E (ApoE) knockout mice, which develop an atherosclerosis-like phenotype. The results of this study show that cardiopulmonary responses to WS exposure occur in a sex-specific manner. EH blunts adverse WS-induced ventilatory responses, specifically an increase in tidal volume (TV), expiratory time (Te), and relaxation time (RT) after a WS exposure, but only in females. EH also blunted an increase in isovolumic relaxation time (IVRT) and the myocardial performance index (MPI) 1-week after exposures, also only in females. Our results suggest that housing alters the cardiovascular response to a single WS exposure, and that DH might cause increased susceptibility to environmental exposures that manifest in altered ventilation patterns and diastolic dysfunction in a sex-specific manner.

Combined effects of heat waves and pesticide pollution on zooplankton communities: Does the timing of stressor matter?

Most studies assessing the combined effects of chemical and non-chemical stressors on aquatic ecosystems have been based on synchronous stressor applications. However, asynchronous exposure scenarios may be more common in nature, particularly for pulsed stressors such as heatwaves and pesticide concentration peaks. In this study, we investigated the single and combined effects of the insecticide chlorpyrifos (CPF) and a heatwave (HW) on a zooplankton community representative of a Mediterranean coastal wetland using synchronous (CPF+HW) and asynchronous (HW→CPF and CPF→HW) exposure scenarios. CPF was applied at a concentration of 0.8 µg/L (single pulse), and the HW was simulated by a temperature increase of 8°C above the control temperature (20°C) for 7 days in freshwater microcosms. The interaction between stressors in synchrony resulted in synergistic effects at the population level (Daphnia magna) and additive at the community level. The partial reduction of sensitive species resulted in an abundance increase of competing species that were more tolerant to the evaluated stressors (e.g. Moina sp.). The asynchronous exposure scenarios resulted in a similar abundance decline of sensitive populations as compared to the synchronous one; however, the timing of stressor resulted in different responses in the long term. In the HW→CPF treatment, the D. magna population recovered at least one month faster than in the CPF+HW treatment, probably due to survival selection and cross-tolerance mechanisms. In the CPF→HW treatment, the effects lasted longer than in the CPF+HW, and the population did not recover within the experimental period, most likely due to the energetic costs of detoxification and effects on internal damage recovery. The different timing and magnitude of indirect effects among the tested asynchronous scenarios resulted in more severe effects on the structure of the zooplankton community in the CPF→HW treatment. Our study highlights the relevance of considering the order of stressors to predict the long-term effects of chemicals and heatwaves both at the population and community levels.

Combined Exposures and Mixtures Research: An Enduring NIEHS Priority.

The National Institute of Environmental Health Sciences (NIEHS) continues to prioritize research to better understand the health effects resulting from exposure to mixtures of chemical and nonchemical stressors. Mixtures research activities over the last decade were informed by expert input during the development and deliberations of the 2011 NIEHS Workshop "Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects." NIEHS mixtures research efforts since then have focused on key themes including a) prioritizing mixtures for study, b) translating mixtures data from in vitro and invivo studies, c) developing cross-disciplinary collaborations, d) informing component-based and whole-mixture assessment approaches, e) developing sufficient similarity methods to compare across complex mixtures, f) using systems-based approaches to evaluate mixtures, and g) focusing on management and integration of mixtures-related data. We aimed to describe NIEHS driven research on mixtures and combined exposures over the last decade and present areas for future attention. Intramural and extramural mixtures research projects have incorporated a diverse array of chemicals (e.g., polycyclic aromatic hydrocarbons, botanicals, personal care products, wildfire emissions) and nonchemical stressors (e.g., socioeconomic factors, social adversity) and have focused on many diseases (e.g., breast cancer, atherosclerosis, immune disruption). We have made significant progress in certain areas, such as developing statistical methods for evaluating multiple chemical associations in epidemiology and building translational mixtures projects that include both in vitro and invivo models. Moving forward, additional work is needed to improve mixtures data integration, elucidate interactions between chemical and nonchemical stressors, and resolve the geospatial and temporal nature of mixture exposures. Continued mixtures research will be critical to informing cumulative impact assessments and addressing complex challenges, such as environmental justice and climate change. https://doi.org/10.1289/EHP14340.

Under pressure: assessment of chemical stress on restored river sections using effect‐based methods

Aquatic ecosystems are affected by multiple stressors, including hydrological and morphological degradation, high nutrient loading, and chemical pollution. To improve freshwater habitats, hydromorphological restorations have been increasingly implemented. However, follow‐up assessments often show little to no improvement in ecological status, even years after restoration measures have been implemented. The success of restoration projects can be compromised by other stressors, such as insufficient water and sediment quality, which often receive less attention compared to nonchemical stressors. In this study, the impact of chemical stress on the outcome of five river restorations was evaluated ecologically, chemically, and ecotoxicologically. Overall, the habitat structure was considerably improved through the restoration measures, whereas the species communities did not show a consistent trend toward an improved ecological status. Effect‐based methods were used for an integrative assessment of the exposure to chemical mixtures in water and sediment samples of restored stream sections. Differences in toxicity between restored and non‐restored sections were found but did not show a consistent trend among the applied assays. In contrast, the chemical analysis showed that the sections of the same stream were similar in their chemical composition, and differences within a stream were primarily due to sediment contamination. The results of this study suggest that chemical pollution is a relevant factor preventing the success of restoration measures and, ultimately, the improvement of the ecological status of rivers. They also demonstrate the applicability of EBMs in water quality monitoring to detect mixture toxicity in streams and link chemical and ecological assessment.

Projection of Interspecific Competition (PIC) Matrices: A Conceptual Framework for Inclusion in Population Risk Assessments.

Accounting for intraspecific and interspecific competition when assessing the effects of chemical and nonchemical stressors is an important uncertainty in ecological risk assessments. We developed novel projection of interspecific competition (PIC) matrices that allow for analysis of population dynamics of two or more species exposed to a given stressor(s) that compete for shared resources within a landscape. We demonstrate the application of PIC matrices to investigate the population dynamics of two hypothetical fish species that compete with one another and have differences in net reproductive rate and intrinsic rate of population increase. Population status predictions were made under scenarios that included exposure to a chemical stressor that reduced fecundity for one or both species. The results of our simulations demonstrated that measures obtained from the life table and Leslie matrix of an organism, including net reproductive rate and intrinsic rate of increase, can result in erroneous conclusions of population status and viability in the absence of a consideration of resource limitation and interspecific competition. This modeling approach can be used in conjunction with field monitoring efforts and/or laboratory testing to link effects due to stressors to possible outcomes within an ecosystem. In addition, PIC matrices could be combined with adverse outcome pathways to allow for ecosystem projection based on taxonomic conservation of molecular targets of chemicals to predict the likelihood of relative cross-species susceptibility. Overall, the present study shows how PIC matrices can integrate effects across the life cycles of multiple species, provide a linkage between endpoints observed in individual and population-level responses, and project outcomes at the community level for multiple generations for multiple species that compete for limited resources. Environ Toxicol Chem 2024;43:1406-1422. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

The Maternal and Infant Environmental Health Riskscape study of perinatal disparities in greater Houston: rationale, study design and participant profiles.

The Maternal and Infant Environmental Health Riskscape (MIEHR) Center was established to address the interplay among chemical and non-chemical stressors in the biological, physical, social, and built environments that disproportionately impact perinatal health among Black pregnant people in a large and diverse urban area with documented disparities in the U.S. The MIEHR cohort is recruiting non-Hispanic Black and non-Hispanic white pregnant people who deliver their infants at major obstetric hospitals in Houston, Texas. At enrollment, all participants are asked to provide urine samples for chemical [metals, cotinine, and polycyclic aromatic hydrocarbons (PAHs)] analyses and blood samples. A subset of the cohort is asked to provide oral and vaginal swabs, and fecal samples. Questionnaire and electronic health record data gather information about residential address history during pregnancy, pregnancy history and prenatal care, sociodemographic and lifestyle factors, experiences of discrimination and stress, and sources of social support. Using information on where a participant lived during their pregnancy, features of their neighborhood environment are characterized. We provide summaries of key individual- and neighborhood-level features of the entire cohort, as well as for Black and white participants separately. Between April 2021 and February 2023, 1,244 pregnant people were recruited. Nearly all participants provided urine samples and slightly less than half provided blood samples. PAH exposure patterns as assessed on 47% of participants thus far showed varying levels depending on metabolite as compared to previous studies. Additionally, analyses suggest differences between Black and white pregnant people in experiences of discrimination, stress, and levels of social support, as well as in neighborhood characteristics. Our findings to date highlight racial differences in experiences of discrimination, stress, and levels of support, as well as neighborhood characteristics. Recruitment of the cohort is ongoing and additional neighborhood metrics are being constructed. Biospecimens will be analyzed for metals and PAH metabolites (urine samples), miRNAs (plasma samples) and the microbiome (oral swabs). Once enrollment ends, formal assessments are planned to elucidate individual- and neighborhood-level features in the environmental riskscape that contribute to Black-White disparities in perinatal health.

Assessing susceptibility for polycyclic aromatic hydrocarbon toxicity in an in vitro 3D respiratory model for asthma.

There is increased emphasis on understanding cumulative risk from the combined effects of chemical and non-chemical stressors as it relates to public health. Recent animal studies have identified pulmonary inflammation as a possible modifier and risk factor for chemical toxicity in the lung after exposure to inhaled pollutants; however, little is known about specific interactions and potential mechanisms of action. In this study, primary human bronchial epithelial cells (HBEC) cultured in 3D at the air-liquid interface (ALI) are utilized as a physiologically relevant model to evaluate the effects of inflammation on toxicity of polycyclic aromatic hydrocarbons (PAHs), a class of contaminants generated from incomplete combustion of fossil fuels. Normal HBEC were differentiated in the presence of IL-13 for 14 days to induce a profibrotic phenotype similar to asthma. Fully differentiated normal and IL-13 phenotype HBEC were treated with benzo[a]pyrene (BAP; 1-40μg/mL) or 1% DMSO/PBS vehicle at the ALI for 48h. Cells were evaluated for cytotoxicity, barrier integrity, and transcriptional biomarkers of chemical metabolism and inflammation by quantitative PCR. Cells with the IL-13 phenotype treated with BAP result in significantly (p < 0.05) decreased barrier integrity, less than 50% compared to normal cells. The effect of BAP in the IL-13 phenotype was more apparent when evaluating transcriptional biomarkers of barrier integrity in addition to markers of mucus production, goblet cell hyperplasia, type 2 asthmatic inflammation and chemical metabolism, which all resulted in dose-dependent changes (p < 0.05) in the presence of BAP. Additionally, RNA sequencing data showed that the HBEC with the IL-13 phenotype may have increased potential for uncontrolled proliferation and decreased capacity for immune response after BAP exposure compared to normal phenotype HBEC. These data are the first to evaluate the role of combined environmental factors associated with inflammation from pre-existing disease and PAH exposure on pulmonary toxicity in a physiologically relevant human in vitro model.

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.

Women's Health Disparities: Spotlight on Nonchemical Stressors, Research Inequities.

Participants in an NIEHS workshop call on researchers, clinicians, publishers, and funders to address racism, environmental disparities, and other factors affecting women's health.

Individual and joint effects of prenatal PM2.5 and maternal stress on child temperament

Prenatal fine particulate matter (PM2.5) and maternal psychological functioning have been associated with child cognitive outcomes, though their independent and joint impacts on earlier behavioral outcomes remains less studied. We used data from 382 mother-child pairs from a prospective birth cohort in Mexico City. Temperament was measured at 24 months using the Carey Toddler Temperament Scale (TTS). Exploratory factor analysis (EFA) was used to update the factor structure of the TTS. During pregnancy, mothers completed the Crisis in Family Systems-Revised, Edinburgh Depression Scale, pregnancy-specific anxiety scale, and the Perceived Stress Scale. Pregnancy PM2.5 was assessed using estimates from a satellite-based exposure model. We assessed the association between prenatal maternal stress and PM2.5 on temperament, in both independent and joint models. Quantile g-computation was used to estimate the joint associations. Models were adjusted for maternal age, SES, education, child sex, and child age. In EFA, we identified three temperament factors related to effortful control, extraversion, and negative affect. Our main results showed that higher levels of PM2.5 and several of the maternal psychological functioning measures were related to both effortful control and negative affect in the child, both individually and as a mixture. For instance, a one quartile increase in the prenatal mixture was associated with higher negative affect scores in the child (0.34, 95% CI: 0.16, 0.53). We observed modification of these associations by maternal SES, with associations seen only among lower SES participants for both effortful control (−0.45, 95% CI: -0.70, −0.20) and negative affect outcomes (0.60, 95% CI: 0.35, 0.85). Prenatal PM2.5 and maternal psychological functioning measures were associated with toddler temperament outcomes, providing evidence for impacts of chemical and non-chemical stressors on early child health.

Broadening the Environmental Lens to Include Social and Structural Determinants of Women's Health Disparities.

Due to the physical, metabolic, and hormonal changes before, during, and after pregnancy, women-defined here as people assigned female at birth-are particularly susceptible to environmental insults. Racism, a driving force of social determinants of health, exacerbates this susceptibility by affecting exposure to both chemical and nonchemical stressors to create women's health disparities. To better understand and address social and structural determinants of women's health disparities, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop focused on the environmental impacts on women's health disparities and reproductive health in April 2022. This commentary summarizes foundational research and unique insights shared by workshop participants, who emphasized the need to broaden the definition of the environment to include upstream social and structural determinants of health. We also summarize current challenges and recommendations, as discussed by workshop participants, to address women's environmental and reproductive health disparities. The challenges related to women's health equity, as identified by workshop attendees, included developing research approaches to better capture the social and structural environment in both human and animal studies, integrating environmental health principles into clinical care, and implementing more inclusive publishing and funding approaches. Workshop participants discussed recommendations in each of these areas that encourage interdisciplinary collaboration among researchers, clinicians, funders, publishers, and community members. https://doi.org/10.1289/EHP12996.

The final ecosystem goods and services Voltron: the power of tools together.

Environmental decision-making benefits from considering ecosystem services to ensure that aspects of the environment that people rely upon are fully evaluated. By focusing consideration of ecosystem services on final ecosystem goods and services (FEGS), the aspects of the environment directly enjoyed, used, or consumed by humans, these analyses can be more streamlined and effective. The U.S. Environmental Protection Agency has developed a set of tools to facilitate this consideration. The central feature of FEGS is that ecosystems are viewed through the diverse ways people directly benefit from them. The National Ecosystem Services Classification System (NESCS) Plus provides a framework for describing and identifying FEGS consistently. The standardization made available by NESCS Plus allows other tools and databases to interact using the NESCS Plus architecture and taxonomy, providing diverse insights for decision makers. Here, we examine the synergy of using the following four tools together: (1) the FEGS Scoping Tool; (2) the FEGS Metrics Report; (3) the EnviroAtlas; and (4) the EcoService Models Library. The FEGS Scoping Tool helps users determine what ecosystem services are relevant to a decision by harnessing FEGS understanding to enable communities to identify the relative importance of beneficiaries relevant to a decision and biophysical aspects of the environment of direct relevance to those beneficiaries. The FEGS Metrics Report can guide which metrics to monitor or model to represent those priority services. The EnviroAtlas, a powerful tool containing geospatial data and other resources related to ecosystem services, chemical and non-chemical stressors, and human health, and the EcoService Models Library, a database of ecosystem models, are two tools that support users in mapping and modeling endpoints relevant to priority services. While each of these tools is valuable on its own, together, they provide a powerful approach to easily incorporate and operationalize ecosystem services efforts into different parts of decision-making processes across different types of decisions. We illustrate how these integrated tools can be used together with a hypothetical example of a complex environmental management case study and the combined benefit of using the FEGS tools together.

Seminar: Scalable Preprocessing Tools for Exposomic Data Analysis.

The exposome serves as a popular framework in which to study exposures from chemical and nonchemical stressors across the life course and the differing roles that these exposures can play in human health. As a result, data relevant to the exposome have been used as a resource in the quest to untangle complicated health trajectories and help connect the dots from exposures to adverse outcome pathways. The primary aim of this methods seminar is to clarify and review preprocessing techniques critical for accurate and effective external exposomic data analysis. Scalability is emphasized through an application of highly innovative combinatorial techniques coupled with more traditional statistical strategies. The Public Health Exposome is used as an archetypical model. The novelty and innovation of this seminar's focus stem from its methodical, comprehensive treatment of preprocessing and its demonstration of the positive effects preprocessing can have on downstream analytics. State-of-the-art technologies are described for data harmonization and to mitigate noise, which can stymie downstream interpretation, and to select key exposomic features, without which analytics may lose focus. A main task is the reduction of multicollinearity, a particularly formidable problem that frequently arises from repeated measurements of similar events taken at various times and from multiple sources. Empirical results highlight the effectiveness of a carefully planned preprocessing workflow as demonstrated in the context of more highly concentrated variable lists, improved correlational distributions, and enhanced downstream analytics for latent relationship discovery. The nascent field of exposome science can be characterized by the need to analyze and interpret a complex confluence of highly inhomogeneous spatial and temporal data, which may present formidable challenges to even the most powerful analytical tools. A systematic approach to preprocessing can therefore provide an essential first step in the application of modern computer and data science methods. https://doi.org/10.1289/EHP12901.

Social-environmental phenotypes of rapid cystic fibrosis lung disease progression in adolescents and young adults living in the United States

BackgroundCystic fibrosis (CF) is a genetic disease but is greatly impacted by non-genetic (social/environmental and stochastic) influences. Some people with CF experience rapid decline, a precipitous drop in lung function relative to patient- and/or center-level norms. Those who experience rapid decline in early adulthood, compared to adolescence, typically exhibit less severe clinical disease but greater loss of lung function. The extent to which timing and degree of rapid decline are informed by social and environmental determinants of health (geomarkers) is unknown. MethodsA longitudinal cohort study was performed (24,228 patients, aged 6–21 years) using the U.S. CF Foundation Patient Registry. Geomarkers at the ZIP Code Tabulation Area level measured air pollution/respiratory hazards, greenspace, crime, and socioeconomic deprivation. A composite score quantifying social-environmental adversity was created and used in covariate-adjusted functional principal component analysis, which was applied to cluster longitudinal lung function trajectories. ResultsSocial-environmental phenotyping yielded three primary phenotypes that corresponded to early, middle, and late timing of peak decline in lung function over age. Geographic differences were related to distinct cultural and socioeconomic regions. Extent of peak decline, estimated as forced expiratory volume in 1 s of % predicted/year, ranged from 2.8 to 4.1 % predicted/year depending on social-environmental adversity. Middle decliners with increased social-environmental adversity experienced rapid decline 14.2 months earlier than their counterparts with lower social-environmental adversity, while timing was similar within other phenotypes. Early and middle decliners experienced mortality peaks during early adolescence and adulthood, respectively. ConclusionWhile early decliners had the most severe CF lung disease, middle and late decliners lost more lung function. Higher social-environmental adversity associated with increased risk of rapid decline and mortality during young adulthood among middle decliners. This sub-phenotype may benefit from enhanced lung-function monitoring and personalized secondary environmental health interventions to mitigate chemical and non-chemical stressors.

Symposium 15: Impact of Environmental Contaminants on Child Neurodevelopment

Summary Abstract:Children are exposed to toxic chemicals throughout development and the long-term consequences of this exposure can be profound. Despite decades of research documenting the vulnerability of the developing brain to environmental contaminants, there has been little progress in protecting against developmental neurotoxicity. This symposium will discuss recent research in developmental neurotoxicology using a "developmental origins of health and disease" (DOHaD) framework that examines the context in which environmental contaminants exert their effects. We will examine the timescale for developmental toxicity, windows of vulnerability, and the bases of individual differences in vulnerability, including sex-specific effects of chemical exposures. This symposium will feature new pregnancy and birth cohort studies that have implicated fluoride as a developmental neurotoxin and endocrine disruptor. In addition, we will discuss emerging issues in epidemiology, including how environmental contaminants may interact with non-chemical stressors and have lifelong impacts on cognition and behaviours. This symposium will be capped with a discussion of the public's knowledge, attitudes, and behaviours related to developmental toxicity and strategies to reduce exposure. All speakers will be asked to draw conclusions on research priorities, and discuss how to balance regulators' need for "ideal evidence" with a public health strategy that aims to protect the public from critical environmental hazards. The symposium will consist of the following five presentations, each 12 minutes in length, followed by a 15 minute discussion.1. John Krzeckowski, PhD, York University, Toronto, Canada.TITLE: Applying a Dimensional Framework to the Study of Developmental Neurotoxicity2. Carly Goodman, PhD candidate, York University, Toronto, CanadaTITLE: Sex difference of Developmental Neurotoxicants on Intellectual abilities: A systematic review and meta-analysis3. Meaghan Hall, PhD candidate, York University, Toronto, Canada.TITLE: Fluoride Exposure and Hypothyroidism in Pregnant Women: A Potential Mechanism of Fluoride Neurotoxicity4. Ashley Malin, PhD, University of Florida,Florida, USA.TITLE: Urinary Fluoride Levels and Metal Co-Exposures among Pregnant Women in Los Angeles, California5. Rivka Green, PhD, The Hospital for Sick Children, Toronto, Canada.TITLE: Translating developmental neurotoxicity for the public: A large, multi-country, randomized-control trial investigating children's environmental health literacy

Multiple stressor effects of insecticide exposure and increased fine sediment deposition on the gene expression profiles of two freshwater invertebrate species

BackgroundFreshwater ecosystem degradation and biodiversity decline are strongly associated with intensive agricultural practices. Simultaneously occurring agricultural stressors can interact in complex ways, preventing an accurate prediction of their combined effects on aquatic biota. Here, we address the limited mechanistic understanding of multiple stressor effects of two globally important stressors, an insecticide (chlorantraniliprole), and increased fine sediment load and assessed their impact on the transcriptomic profile of two stream macroinvertebrates: the amphipod Gammarus pulex and the caddisfly Lepidostoma basale.ResultsWe identified mainly antagonistic stressor interactions at the transcriptional level, presumably because the insecticide adsorbed to fine sediment particles. L. basale, which is phylogenetically more closely related to the insecticide’s target taxon Lepidoptera, exhibited strong transcriptional changes when the insecticide stressor was applied, whereas no clear response patterns were observed in the amphipod G. pulex. These differences in species vulnerability can presumably be attributed to molecular mechanisms determining the cellular affinity toward a stressor as well as differential exposure patterns resulting from varying ecological requirements between L. basale and G. pulex. Interestingly, the transcriptional response induced by insecticide exposure in L. basale was not associated with a disruption of the calcium homeostasis, which is the described mode of action for chlorantraniliprole. Instead, immune responses and alterations of the developmental program appear to play a more significant role.ConclusionsOur study shows how transcriptomic data can be used to identify multiple stressor effects and to explore the molecular mechanisms underlying stressor-induced physiological responses. As such, stressor effects assessed at the molecular level can inform about modes of action of chemicals and their interplay with non-chemical stressors. We demonstrated that stressor effects vary between different organismic groups and that insecticide effects are not necessarily covered by their described mode of action, which has important implications for environmental risk assessment of insecticides in non-target organisms.

Preliminary Analysis of Chemical and Non-Chemical Stressors Collected from Mother-Child Pairs in the National Children’s Study

Preliminary Analysis of Chemical and Non-Chemical Stressors Collected from Mother-Child Pairs in the National Children’s Study