Community-level exposomics: a population-centered approach to address public health concerns.

Environmental factors affecting health and vulnerability far outweigh genetics in accounting for disparities in health status and longevity in US communities. The concept of the exposome, the totality of exposure from conception onwards, provides a paradigm for researchers to investigate the complex role of the environment on the health of individuals. We propose a complementary framework, community-level exposomics, for population-level exposome assessment. The goal is to bring the exposome paradigm to research and practice on the health of populations, defined by various axes including geographic, social, and occupational. This framework includes the integration of community-level measures of the built, natural and social environments, environmental pollution-derived from conventional and community science approaches, internal markers of exposure that can be measured at the population-level and early responses associated with health status that can be tracked using population-based monitoring. Primary challenges to the implementation of the proposed framework include needed advancements in population-level measurement, lack of existing models with the capability to produce interpretable and actionable evidence and the ethical considerations of labeling geographically-bound populations by exposomic profiles. To address these challenges, we propose a set of recommendations that begin with greater engagement with and empowerment of affected communities and targeted investment in community-based solutions. Applications to urban settings and disaster epidemiology are discussed as examples for implementation.

Integrating Environment and Aging Research: Opportunities for Synergy and Acceleration.

Despite significant overlaps in mission, the fields of environmental health sciences and aging biology are just beginning to intersect. It is increasingly clear that genetics alone does not predict an individual's neurological aging and sensitivity to disease. Accordingly, aging neuroscience is a growing area of mutual interest within environmental health sciences. The impetus for this review came from a workshop hosted by the National Academies of Sciences, Engineering, and Medicine in June of 2020, which focused on integrating the science of aging and environmental health research. It is critical to bridge disciplines with multidisciplinary collaborations across toxicology, comparative biology, epidemiology to understand the impacts of environmental toxicant exposures and age-related outcomes. This scoping review aims to highlight overlaps and gaps in existing knowledge and identify essential research initiatives. It begins with an overview of aging biology and biomarkers, followed by examples of synergy with environmental health sciences. New areas for synergistic research and policy development are also discussed. Technological advances including next-generation sequencing and other-omics tools now offer new opportunities, including exposomic research, to integrate aging biomarkers into environmental health assessments and bridge disciplinary gaps. This is necessary to advance a more complete mechanistic understanding of how life-time exposures to toxicants and other physical and social stressors alter biological aging. New cumulative risk frameworks in environmental health sciences acknowledge that exposures and other external stressors can accumulate across the life course and the advancement of new biomarkers of exposure and response grounded in aging biology can support increased understanding of population vulnerability. Identifying the role of environmental stressors, broadly defined, on aging biology and neuroscience can similarly advance opportunities for intervention and translational research. Several areas of growing research interest include expanding exposomics and use of multi-omics, the microbiome as a mediator of environmental stressors, toxicant mixtures and neurobiology, and the role of structural and historical marginalization and racism in shaping persistent disparities in population aging and outcomes. Integrated foundational and translational aging biology research in environmental health sciences is needed to improve policy, reduce disparities, and enhance the quality of life for older individuals.

The Environmental Protection Agency's Community-Focused Exposure and Risk Screening Tool (C-FERST) and its potential use for environmental justice efforts.

OBJECTIVES: Our primary objective was to provide higher quality, more accessible science to address challenges of characterizing local-scale exposures and risks for enhanced community-based assessments and environmental decision-making. METHODS: After identifying community needs, priority environmental issues, and current tools, we designed and populated the Community-Focused Exposure and Risk Screening Tool (C-FERST) in collaboration with stakeholders, following a set of defined principles, and considered it in the context of environmental justice. RESULTS: C-FERST is a geographic information system and resource access Web tool under development for supporting multimedia community assessments. Community-level exposure and risk research is being conducted to address specific local issues through case studies. CONCLUSIONS: C-FERST can be applied to support environmental justice efforts. It incorporates research to develop community-level data and modeled estimates for priority environmental issues, and other relevant information identified by communities. Initial case studies are under way to refine and test the tool to expand its applicability and transferability. Opportunities exist for scientists to address the many research needs in characterizing local cumulative exposures and risks and for community partners to apply and refine C-FERST.

Adopting a "Compound" Exposome Approach in Environmental Aging Biomarker Research: A Call to Action for Advancing Racial Health Equity.

BACKGROUND: In June 2020, the National Academies of Sciences, Engineering, and Medicine hosted a virtual workshop focused on integrating the science of aging and environmental health research. The concurrent COVID-19 pandemic and national attention on racism exposed shortcomings in the environmental research field's conceptualization and methodological use of race, which have subsequently hindered the ability of research to address racial health disparities. By the workshop's conclusion, the authors deduced that the utility of environmental aging biomarkers-aging biomarkers shown to be specifically influenced by environmental exposures-would be greatly diminished if these biomarkers are developed absent of considerations of broader societal factors-like structural racism-that impinge on racial health equity. OBJECTIVES: The authors reached a post-workshop consensus recommendation: To advance racial health equity, a "compound" exposome approach should be widely adopted in environmental aging biomarker research. We present this recommendation here. DISCUSSION: The authors believe that without explicit considerations of racial health equity, people in most need of the benefits afforded by a better understanding of the relationships between exposures and aging will be the least likely to receive them because biomarkers may not encompass cumulative impacts from their unique social and environmental stressors. Employing an exposome approach that allows for more comprehensive exposure-disease pathway characterization across broad domains, including the social exposome and neighborhood factors, is the first step. Exposome-centered study designs must then be supported with efforts aimed at increasing the recruitment and retention of racially diverse study populations and researchers and further "compounded" with strategies directed at improving the use and interpretation of race throughout the publication and dissemination process. This compound exposome approach maximizes the ability of our science to identify environmental aging biomarkers that explicate racial disparities in health and best positions the environmental research community to contribute to the elimination of racial health disparities. https://doi.org/10.1289/EHP8392.

Long-term perchloroethylene exposure: a meta-analysis of neurobehavioral deficits in occupationally and residentially exposed groups.

The literature concerning the neurobehavioral and neurophysiological effects of long-term exposure to perchloroethylene (PERC) in humans was meta-analyzed to provide a quantitative review and synthesis in the form of dose-effect curves. The useable database from this literature comprised studies reporting effects of long-term exposure to PERC, effects that included slowed reaction times, cognitive deficits, impaired color vision, and reduced visual contrast sensitivity. For the meta-analyses, dose was defined as the product of the concentration inhaled PERC and the duration of exposure, expressed in unites of ppm-h/1000 (for numerical convenience). Dose-related results were highly variable across studies. Reports involving low exposure concentrations characteristic of nonoccupational exposures consistently produced effects of a magnitude that were comparable to those reported for higher concentration occupational studies. If this finding is reliable and general, studies of occupationally exposed persons may underestimate the magnitude of effects of PERC and other chemicals in the total population. Given the limited scope of the available data for PERC and its methodological and reporting problems (small sample sizes, testers were not blind to the subjects' exposure conditions, and the timing and location of testing were insufficiently documented), it seems important to test this conclusion with a well-documented study of two groups (occupational and nonoccupational exposure) in which subjects are evaluated in randomized order, using the same procedures and with the testers kept blind to the status of the subjects.

Electroretinographic features of the retinopathy, globe enlarged (rge) chick phenotype.

PURPOSE: The purpose of the study was to characterize the electroretinographic features of the autosomal recessive retinopathy, globe enlarged (rge) phenotype, in chickens (Gallus gallus). METHODS: Dark-adapted, light-adapted intensity series and light-adapted 30 Hz flicker responses were recorded from rge and age matched normal control chicks from one to 270 days of age. Retinal sections from rge and control retinas were examined in 7 and 270-day-old chicks. RESULTS: Electroretinogram (ERG) thresholds of rge birds were raised, the intensity response plots were shifted toward brighter intensities, and retinal sensitivity was reduced. The leading slope of the dark- and light-adapted a-waves was more shallow than normal, suggesting altered photoreceptor responses. The inner retinal components to the ERG were also abnormal; there was a marked lack of oscillatory potentials and an abnormally smooth and broad shape to the b-wave. Additionally, the b-wave was supernormal in response to brighter stimuli in the earlier stages of the disease. There was a progressive deterioration in ERG amplitudes with age that mirrored a slowly progressive thinning of the photoreceptor layer. CONCLUSIONS: The rge chicken has unusual ERG changes from an early age with altered waveforms and initially they develop a supernormal b-wave. This is followed by a progressive reduction of ERG amplitudes with age. The changes suggest that both photoreceptor and inner retinal responses are abnormal. Additional studies are needed to further elucidate the origin of the abnormal ERG components in the rge chick.

Integrating epidemiology and toxicology in neurotoxicity risk assessment.

Neurotoxicity risk assessments depend on the best available scientific information, including data from animal toxicity studies, human experimental studies and human epidemiology studies. There are several factors to consider when evaluating the comparability of data from studies. Regarding the epidemiology literature, issues include choice of study design, use of appropriate controls, methods of exposure assessment, subjective or objective evaluation of neurological status, and assessment and statistical control of potential confounding factors, including co-exposure to other agents. Animal experiments must be evaluated regarding factors such as dose level and duration, procedures used to assess neurological or behavioural status, and appropriateness of inference from the animal model to human neurotoxicity. Major factors that may explain apparent differences between animal and human studies include: animal neurological status may be evaluated with different procedures than those used in humans; animal studies may involve shorter exposure durations and higher dose levels; and most animal studies evaluate a single substance whereas humans typically are exposed to multiple agents. The comparability of measured outcomes in animals and humans may be improved by considering functional domains rather than individual test measures. The application of predictive models, weight of evidence considerations and meta-analysis can help evaluate the consistency of outcomes across studies. An appropriate blend of scientific information from toxicology and epidemiology studies is necessary to evaluate potential human risks of exposure to neurotoxic substances.

Induction of asthma and the environment: what we know and need to know.

The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop "Environmental Influences on the Induction and Incidence of Asthma" to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment.

Toluene inhalation exposure for 13 weeks causes persistent changes in electroretinograms of Long-Evans rats.

Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000ppm toluene by inhalation (6hr/d, 5d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m(2)) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000ppm toluene for 4 weeks were tested approximately 1year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensitive to organic solvent exposure than the rat visual cortex.

Aging and the environment: a research framework.

The rapid growth in the number of older Americans has many implications for public health, including the need to better understand the risks posed to older adults by environmental exposures. Biologic capacity declines with normal aging; this may be exacerbated in individuals with pre-existing health conditions. This decline can result in compromised pharmacokinetic and pharmacodynamic responses to environmental exposures encountered in daily activities. In recognition of this issue, the U.S. Environmental Protection Agency (EPA) is developing a research agenda on the environment and older adults. The U.S. EPA proposes to apply an environmental public health paradigm to better understand the relationships between external pollution sources --> human exposures --> internal dose --> early biologic effect --> adverse health effects for older adults. The initial challenge will be using information about aging-related changes in exposure, pharmacokinetic, and pharmacodynamic factors to identify susceptible subgroups within the diverse population of older adults. These changes may interact with specific diseases of aging or medications used to treat these conditions. Constructs such as "frailty" may help to capture some of the diversity in the older adult population. Data are needed regarding a) behavior/activity patterns and exposure to the pollutants in the microenvironments of older adults; b) changes in absorption, distribution, metabolism, and excretion with aging; c) alterations in reserve capacity that alter the body's ability to compensate for the effects of environmental exposures; and d) strategies for effective communication of risk and risk reduction methods to older individuals and communities. This article summarizes the U.S. EPA's development of a framework to address and prioritize the exposure, health effects, and risk communications concerns for the U.S. EPA's evolving research program on older adults as a susceptible subpopulation.

Human neurobehavioral effects of long-term exposure to styrene: a meta-analysis.

Many reports in the literature suggest that long-term exposure to styrene may exert a variety of effects on the nervous system, including increased choice reaction time and decreased performance of color discrimination and color arrangement tasks. Sufficient information exists to perform a meta-analysis of these observations quantifying the relationships between exposure (estimated from biomarkers) and effects on two measures of central nervous system function: reaction time and color vision. To perform the meta-analysis, we pooled data into a single database for each end point. End-point data were transformed to a common metric of effect magnitude (percentage of baseline). We estimated styrene concentration from biomarkers of exposure and fitted linear least-squares equations to the pooled data to produce dose-effect relationships. Statistically significant relationships were demonstrated between cumulative styrene exposure and increased choice reaction time as well as increased color confusion index. Eight work-years of exposure to 20 ppm styrene was estimated to produce a 6.5% increase in choice reaction time, which has been shown to significantly increase the probability of automobile accidents. The same exposure history was predicted to increase the color confusion index as much as 1.7 additional years of age in men.

Homology of assessment of visual function in human and animal models.

To connect animal models with human neurobehavioral evaluations, it is necessary to understand the level of homology present between tests administered across species. This paper identifies four different levels of homology of assessment based on identity of measurement, function, and underlying neural substrate. These are discussed using detailed examples from toxicology of the visual system, with additional examples from tests of motor and cognitive function. This should provide a framework for considering both animal to human extrapolation and human to animal extrapolation, that is, how to import human experimental epidemiology findings into the lab for further work investigating mechanisms of toxicity. Designing neurobehavioral or sensory evaluations that permit easier extrapolation between human and animal models is necessary if we are to develop testing strategies that take advantage of mechanistic information at whole animal, in vitro, proteonomic, or genomic levels.

Increased ERG a- and b-wave amplitudes in 7- to 10-year-old children resulting from prenatal lead exposure.

PURPOSE: To determine the dose-response relationship between blood lead concentration ([PbB]) and scotopic ERG amplitude in 7- to 10-year-old children with lifetime lead exposure. METHODS: Full-field flash scotopic ERGs were recorded over a 4-log-unit range in 45 dark-adapted children with normal visual acuity. [PbB] was measured throughout pregnancy and postnatal development, and the subjects' [PbB] levels were grouped at each age by tertiles. RESULTS: The median [PbB] during pregnancy was, from lowest to highest tertile, 2.5 to 5.0, 7.5 to 9.0, and 14.0 to 16.5 microg/dL, and after birth was 4.0 to 8.0, 6.0 to 14.5, and 7.5 to 21.0 microg/dL. Only maternal [PbB] at 12 weeks of pregnancy showed a significant dose-response relationship with the ERG measures, so that with increasing [PbB] there were significant increases in leading-edge a-wave amplitude, peak a-wave amplitude, and b-wave amplitude and sensitivity, with no changes in implicit times. Data analyses showed that children whose mothers had [PbB] of 10.5 microg/dL or more at 12 weeks of pregnancy had relatively increased a- and b-waves. CONCLUSIONS: Lead exposure during the first trimester of pregnancy produces dose-dependent increases in scotopic a- and b-wave amplitudes in 7- to 10-year-old children. The results suggest that the increases in a- and b-wave amplitudes originate from rods; however, the increased b-wave amplitude and sensitivity may also originate in the inner retina. These alterations occurred at maternal [PbB] at or below currently accepted safe levels. These novel findings reveal that the developing retina is a sensitive target for lead and suggest that lead-exposed children be examined for possible future visual system deficits.

Apartment residents' and day care workers' exposures to tetrachloroethylene and deficits in visual contrast sensitivity.

Tetrachloroethylene (also called perchloroethylene, or perc), a volatile organic compound, has been the predominant solvent used by the dry-cleaning industry for many years. The U.S. Environmental Protection Agency (EPA) classified perc as a hazardous air pollutant because of its potential adverse impact on human health. Several occupational studies have indicated that chronic, airborne perc exposure adversely affects neurobehavioral functions in workers, particularly visual color discrimination and tasks dependent on rapid visual-information processing. A 1995 study by Altmann and colleagues extended these findings, indicating that environmental perc exposure at a mean level of 4,980 microg/m(3) (median=1,360 microg/m(3)) alters neurobehavioral functions in residents living near dry-cleaning facilities. Although the U.S. EPA has not yet set a reference concentration guideline level for environmental exposure to airborne perc, the New York State Department of Health set an air quality guideline of 100 microg/m(3). In the current residential study, we investigated the potential for perc exposure and neurologic effects, using a battery of visual-system function tests, among healthy members of six families living in two apartment buildings in New York City that contained dry-cleaning facilities on the ground floors. In addition, a day care investigation assessed the potential for perc exposure and effects among workers at a day care center located in the same one-story building as a dry-cleaning facility. Results from the residential study showed a mean exposure level of 778 microg/m(3) perc in indoor air for a mean of 5.8 years, and that perc levels in breath, blood, and urine were 1-2 orders of magnitude in excess of background values. Group-mean visual contrast sensitivity (VCS), a measure of the ability to detect visual patterns, was significantly reduced in the 17 exposed study participants relative to unexposed matched-control participants. The groups did not differ in visual acuity, suggesting that the VCS deficit was of neurologic origin. Healthy workers in the day care investigation were chronically exposed to airborne perc at a mean of 2,150 microg/m(3) for a mean of 4.0 years. Again, group-mean VCS, measured 6 weeks after exposure cessation, was significantly reduced in the nine exposed workers relative to matched controls, and the groups did not differ significantly in visual acuity. These results suggested that chronic, environmental exposure to airborne perc adversely affects neurobehavioral function in healthy individuals. Further research is needed to assess the susceptibility of the young and elderly to perc-induced effects, to determine whether persistent solvent-induced VCS deficits are a risk factor for the development of neurologic disease, and to identify the no observable adverse effect level for chronic, environmental, perc exposure in humans.

Analysis of NHANES measured blood PCBs in the general US population and application of SHEDS model to identify key exposure factors.

Studies have shown that the US population continues to be exposed to polychlorinated biphenyls (PCBs), despite their ban more than three decades ago, but the reasons are not fully understood. The objectives of this paper are to characterize patterns of PCBs in blood by age, gender, and ethnicity, and identify major exposure factors. EPA's Stochastic Human Exposure and Dose Simulation (SHEDS)-dietary exposure model was applied, combining fish tissue PCB levels from a NYC Asian Market survey with National Health and Nutrition Examination Survey (NHANES) dietary consumption data, and then linked with blood biomarkers for the same NHANES study subjects. Results reveal that the mean concentration of total PCBs in blood was higher with increasing age; however, for the same age, gender, and ethnicity, the blood PCB concentrations measured in the later NHANES survey were significantly lower than those in the earlier one. The decrease within an age group between the two survey periods lessened with increasing age. Blood PCBs among different ethnicities ranked differently between the older and the younger age groups within each survey. Non-Hispanic Blacks had significantly higher blood PCBs for the >30 year age group. For the 12 to ≤30 year age group, the "Asian, Pacific Islander, Native American or multiracial" group had the highest values, with patterns fairly consistent with fish consumption and modeled PCB exposure patterns. We conclude that for younger people, patterns correspond to reduced environmental contamination over time, and are strongly associated with fish consumption and dietary exposures. Higher PCB concentrations in blood of the older population may partially reflect past exposures to higher environmental PCB concentrations, particularly before the ban.

GPS-based microenvironment tracker (MicroTrac) model to estimate time-location of individuals for air pollution exposure assessments: model evaluation in central North Carolina.

A critical aspect of air pollution exposure assessment is the estimation of the time spent by individuals in various microenvironments (ME). Accounting for the time spent in different ME with different pollutant concentrations can reduce exposure misclassifications, while failure to do so can add uncertainty and bias to risk estimates. In this study, a classification model, called MicroTrac, was developed to estimate time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from global positioning system (GPS) data and geocoded building boundaries. Based on a panel study, MicroTrac estimates were compared with 24-h diary data from nine participants, with corresponding GPS data and building boundaries of home, school, and work. MicroTrac correctly classified the ME for 99.5% of the daily time spent by the participants. The capability of MicroTrac could help to reduce the time-location uncertainty in air pollution exposure models and exposure metrics for individuals in health studies.