In this report, the committee has evaluated the status of exposure science and how the field is poised to play a more critical role in addressing the important human health and ecologic challenges of the future. The committee’s analyses established that exposure science is essential for protecting human and ecosystem health by informing decisions about prevention and mitigation of adverse exposures and by enabling sustainable innovations. The committee expanded the vision of exposure science to the eco-exposome. Adoption of this concept will lead to the development of a universal exposure-tracking framework that allows for the creation of an exposure narrative and the prediction of virtually all biologically-relevant human and ecologic exposures, leading to improved exposure information for making informed decisions to protect human and ecosystem health.
With better exposure information, the field has the ability to address multiple and complex scientific, societal, commercial, and policy demands. To provide the level and quality of exposure information on the scale required by those demands, the collection of relevant information—with both traditional established methods, such as pollution-monitoring networks, and emerging methods, such as those in exposure biology and in application of cellular-telephone networks—needs to be improved. In addition, it will become important to take advantage of advances in related fields of science, including biology, informatics, and microsensor technologies.
The increasingly complex global-scale interactions among the built and natural environments call for better, faster, and less-expensive exposure information. Such information is essential for managing health and environmental risks, protecting vulnerable populations, and developing innovative and sustainable solutions to prevent exposures to adverse stressors and to promote exposures to beneficial ones.
Embedded in the committee’s vision is the recognition of the integrative nature of human and environmental systems. There are no boundaries between organisms (including humans) and their environment or between the internal environment of the human body and the external environment. Historically, exposure research has focused on discrete exposures—in either external or internal environments, concentrating on effects from sources on biologic systems, either human or ecologic—one stressor at a time. As a result, tools and methods evolved, and resources were channeled to address specific measures.
To fulfill its vision, the committee has identified the following overarching research needs in exposure science:
• Characterizing exposures quickly and cost-effectively at multiple levels of integration—including time, space, and biologic scales—and for multiple and cumulative stressors.
• Scaling up methods and techniques to detect exposure in large human and ecologic populations of concern.
The broader availability and ease of use of technologies, including sensor, analytic, bioinformatic, and computational technologies, have given rise to a substantial profusion of data and an overall democratization of the collection and availability of exposure information. The Centers for Disease Control and Prevention (CDC) National Human and Nutrition Examination Survey (NHANES) provides one of the most revealing snapshots of human exposures to over 200 environmental chemicals through the use of biomonitoring (CDC 2011). The collaboration between CDC and national and international organizations quickly expanded the breadth and depth of data available throughout populations and subpopulations (NRC 2006). That rapid progress was predicated on the availability of better analytic methods and a national commitment to generate such “baseline” data.
With the availability of the emerging measurement and informatics technologies, the committee sees both the demand and the opportunity for conducting strategic data-gathering efforts to answer a multitude of environmental-exposure questions. Such efforts could involve deploying large numbers of environmental sensors and networking technologies and collecting biomonitoring samples in statistically representative populations. The resulting data could be integrated with informatics capabilities for collection, storing, and analyzing the information gathered and used to test environmental-health-related hypotheses or to develop exposure-reduction strategies.
The committee recognizes that realizing its vision requires an iterative approach that will initially develop and implement innovative tools to meet the urgent demands for exposure information today while establishing the infrastructure, including educational opportunities and study sections devoted to research, needed to transform the science fully over the next 20 years. This chapter describes a pragmatic approach to realizing the vision for exposure science in the 21st century whereby resources are deployed to generate and analyze the
maximum amount of exposure information and to develop effective and relevant applications of such information. One important objective should be to describe, reconstruct, and forecast real-world exposures more accurately and more efficiently. To be effective, exposure science needs to adopt a systems-based approach that, to the extent possible, considers exposures from source to dose and from dose to source and considers multiple levels of integration, including time, space, and biologic scales in connection with multiple stressors in human and ecosystem populations.
In the near term, exposure science needs to develop strategies to expand exposure information rapidly to improve understanding of where, when, and how exposures occur and their health significance. Data generated and collected would be used to evaluate and improve models of exposure for use in generating hypotheses and developing policies. New exposure infrastructure (for example, sensor networks, environmental monitoring, activity tracking, and data storage and distribution systems) will help to refine or replace existing measurement and monitoring strategies. This process will help to identify the largest knowledge gaps and reveal where gathering of more exposure information would contribute the most to reducing uncertainty.
In the field of environmental health, substantial investment and progress have been made in recent years to collect and improve access to genomic, toxicology, and health data (for example, Davis et al. 2011; CTD 2012) and to provide information on chemical toxicity and inform and guide research. However, those data have historically lacked the extensive and reliable exposure information required for examining environmental contributions to diseases and assessing health risks. The Environmental Protection Agency (EPA) ExpoCast program, initiated to address that research gap, is intended to advance the characterization of exposures to support toxicity testing (Cohen Hubal et al. 2010a) and in the long term to link exposures to health outcomes. There is still a growing demand to collect more exposure data to populate emerging exposure databases (for example, Gangwal 2011) and to facilitate linkages with toxicity and environmental-fate data and with manufacturers’ production and use data.
An Exposure Infostructure
Exposure data are often scattered among such widely dispersed sources that it is difficult to relate them (Egeghy et al. 2012). Several initiatives in the United States and abroad aim at developing tools to integrate those data sources
1“Data landscape” is a term used in informatic and computational analyses. The term implies stepping back and looking at the data available, identifying data rich and data poor areas, and seeing what the data “landscape” looks like.
(for example, Mattingly et al. 2012), but more efforts are needed. The tools will help in the systematic mining of databases and scientific literature that contain millions of observations and are intended to bridge the gap between exposure science and other environmental-health disciplines, including toxicology, epidemiology, disease surveillance, and epigenetics.
Efforts to develop and enhance exposure information can contribute to the development of an exposure infostructure and data-sharing approaches that in turn can influence the design of exposure and environmental-health studies. In such fields as genomics, computational toxicology, environmental toxicology, and cancer research, creation of infostructures has resulted in groundbreaking and transformative innovations in research methods and approaches. A strategic approach to populating the exposure knowledge base effectively will motivate research that informs our understanding of exposures at biologic scales, time durations, and locations. Consideration of the uncertainty and variability of measurements and models is critical because data will be gathered from disparate sources and will influence our understanding of health and ecosystem effects.
Developing and Empowering Computational Approaches
Environmental fate and transport models are used to estimate and predict environmental concentrations. However, the models are hampered by the absence of data that can be used to evaluate some of the model parameters and ultimately estimate the relevance and robustness of their predictions (MacLeod et al. 2010). Data in the exposure infostructure can be used to cross-validate the models against one another and bridge knowledge gaps. The models can then be developed further to predict exposures to a large number of chemicals or other stressors individually or in combination and among microenvironments. For example, Aylward and Hays (2011) used data from the NHANES biomonitoring program and pharmacokinetic studies, integrated with in vitro toxicity data from specific chemical case studies, to examine the physiologic relevance of tested in vitro concentrations and thereby helped to inform dosimetry in evaluating ToxCast data. Efforts to determine how exposure models could be adapted to advance high-throughput chemical priority-setting and risk assessment have been hindered in part by absence of or lack of access to high-quality exposure data (Cohen Hubal et al. 2010a; Egeghy et al. 2012).
Integrating Surveillance Systems
Responding to the demand for exposure data requires creative and parsimonious approaches for data generation and collection. The opportunities provided by existing and emerging surveillance networks and technologies to gather direct exposure information or information on relevant surrogates can improve our assessment of exposures, for example, by combining food samples and soil
samples and linking ecologic surveys with food-web analysis to evaluate exposure models for complex food-pathway exposures. In the near term, an important research goal will be to identify the diversity of existing surveillance systems to improve our knowledge of data on environmental contaminants. Specifically, researchers will need to address the following questions: How can these surveillance systems be used to provide baseline information on exposure? How can resources be marshaled to obtain such data? What efforts can be made to develop surveillance systems, in particular ones that will integrate ecologic surveillance data with human health data. One large-scale example is the CDC National Environmental Public Health Tracking Network (National EPHT Network), which collects information relevant for assessing environmental exposures and associated health outcomes and develops the infrastructure needed for analyzing and integrating such information for public-health protection. That effort faces many challenges—the network includes 23 states—but the National EPHT Network constitutes the largest effort to track environmental exposures that are likely to contribute to disease.
When hot spots or places of highest potential impact to vulnerable and susceptible populations are identified, targeted studies need to be designed for more detailed measurements. That will expand applications of exposure science to specific studies that can lead to exposure reduction or source mitigation. It can also include the development of new tools.
In essence, advances in technologies and bioinformatics provide a plethora of opportunities to link existing surveillance systems and data infrastructures and to enrich them with targeted exposure-measurement studies that will promote the development of an exposure infostructure that increases our understanding of health and ecologic impacts of environmental exposures.
A Predictive Exposure Network
The combination of surveillance programs and targeted exposure-measurement programs is integral to the strategy for building a predictive exposure network that can address environmental-health questions. Information from the network could be used to develop exposure metrics that will provide the information needed for evaluating the overall health and resilience of humans and ecosystems, identifying vulnerable populations, assessing the impact of cumulative exposures, and addressing exposure disparities. It could also be used to assess environmental improvements and to provide early warnings of emerging problems. More data on exposures will allow us to forecast, prevent, and mitigate the impacts of such major societal challenges as climate change, security threats, and urbanization.
Given the explosion of technologies and knowledge systems, this incremental, iterative, and adaptive approach to developing a network is feasible even in a resource-constrained environment. It will require modest resources and a commitment from the community of exposure scientists.
A major demand for exposure information comes from efforts to modernize chemical-management policies in the United States and abroad, including the European Commission’s Registration, Evaluation, and Authorization of Chemicals (REACH) regulation, the Green Chemistry Initiative in California, the sustainability program in EPA, and efforts to revise the Toxic Substances Control Act. Those efforts have highlighted the need for tools for assessing and measuring exposures to a large number of chemicals currently on the market and others that are emerging and likely to become ubiquitous, such as nanomaterials. In addition, there is a need for improved understanding of multiple exposures and tools for assessing biologically relevant exposures, particularly during critical life stages. The confluence of interests with recent advances in biology, toxicology, and computational tools provides opportunities to advance exposure assessment.
Setting Priorities among Exposures
There is a need to characterize potential risk to human and ecosystem health that arises from the manufacture and use of tens of thousands of chemicals (Cohen Hubal 2010b). EPA’s ToxCast program is applying new technologies to screen and set priorities among chemicals for toxicity. EPA has developed methods for using high-throughput screening and toxicogenomic technologies to predict potential toxicity and to set priorities for the use of testing resources (Cohen Hubal 2008). In a parallel effort, ExpoCast is aiming to develop the required exposure-science data and tools for addressing immediate needs for rapid characterization of exposure potential for priority-setting and chemical-risk management. Through ExpoCast, EPA’s Office of Research and Development aims to develop novel approaches and metrics for chemical screening and evaluation based on biologically relevant human exposures (Little et al. 2011).
EPA’s National Center for Computational Toxicology has proposed a Toxicological Priority Index (ToxPi) designed to integrate multiple domains of knowledge to inform chemical priority-setting (EPA 2011). The ToxPi framework is flexible, can incorporate new data from diverse sources, and provides an opportunity to enrich priority-setting related to potential hazards with exposure information (Reif et al. 2010; Little et al. 2011).
Combining exposure priority-setting information with hazard information, such as that derived from ToxCast, will help in establishing priorities among chemicals for evaluation on the basis of their potential for harming human health. With that information, it will be possible to develop exposure assessments that can identify the appropriate type of information and the level of detail needed to address the risk-assessment and risk-management questions at hand.
Assessing and Quantifying Multiple Exposures
To assess the outcomes of multiple exposures (that is, both exogenous and endogenous stressors), there is a need to understand the joint behavior of these stressors, the interactions among them, and their contributions to health outcomes. This includes research to address interactions among chemical, physical, and biologic stressors, along with social stressors. Understanding the sources of these stressors can allow for intervention to prevent exposures or to mitigate their effects.
Although it is possible to test the toxicity of mixtures of chemicals (and perhaps other stressors), the tests tend to be based on ad hoc combinations typically of two chemicals and are often not very representative of real-world exposures. In a recent analysis, researchers in EPA investigated methods from the field of community ecology originally developed to study avian species co-occurrence patterns and adapted them to examine chemical co-occurrence (Tornero-Velez et al. 2012). Their findings showed that chemical co-occurrence was not random but was highly structured and usually resulted in specific combinations that were predictable with models. Novel application of tools and approaches from a variety of research disciplines can be used to address the complexity of mixtures, advance our understanding of exposures to them, and promote the design of relevant experiments and models to assess their health risks.
Characterizing or Quantifying Biologically Relevant Exposures
Systems approaches to understanding human biology together with knowledge of systems-level perturbations caused by human—environment interactions are critical for understanding biologically relevant exposures (Farland 2010). Understanding how early perturbations of biologic pathways can lead to disease requires information gathered over a lifetime. In addition, applying such concepts as the exposome effectively demands exposure information that is predictive of disease. The connection between exposure information for understanding early perturbations of biologic pathways and for predicting disease carries enormous promise for better ways of linking exposure and disease and ultimately for informing design of relevant studies. The development of advanced technologies to measure key exposure metrics that include biomarkers for assessing internal exposures and sensors to measure personal exposure needs to be supported to achieve a better understanding of exposure—response relationships (Cohen Hubal 2009). Integrated application of the technologies in specific situations will help to elucidate the exposures that are relevant to biologic effects of environmental hazards. Such applications will allow us to assess the effects of aggregate and cumulative exposures on health.
Such efforts are currently funded under the National Institute of Environmental Health Sciences (NIEHS) Exposure Biology Program2 (NIEHS 2009), and related efforts are funded by EPA and other federal agencies. These novel biomarker technologies are still in their infancy and require resources for developing them, scaling them, and validating them for population studies. An incremental and iterative approach to creating opportunities for transdisciplinary research, cross-study sharing, and validation of tools and data will help to advance their progress.
Exposure information is needed to advance environmental-health research. Because of the relative scarcity of exposure data and the high cost of collecting them, environmental-health analyses and decisions have often been based on narrowly limited or low-quality data. However, as discussed earlier (see Chapter 1), the absence of such data has had unintended consequences (for example, Graham 2011). The demand for exposure information, coupled with the development of tools and approaches for collecting and analyzing such data, has created an opportunity to transform exposure science to advance human and ecosystem health.
The transformation will require an investment of resources and a substantial shift in how exposure science research is deployed and implemented.
To implement its vision, the committee identified research needs that call for new methods and approaches, validation of methods and their enhancement for application on different scales and in broader circumstances, and improved linkages to research in other sectors of the environmental-health sciences. The research needs are organized into several broad categories: providing effective responses to immediate or short-term threats to health and the environment; supporting research on health and ecologic effects to understand past, current, and emerging outcomes; and addressing demands for exposure information from communities, government, and industry. The research needs are organized by priority within each category on the basis of the time that will be required for their development and implementation: short term denotes less than 5 years, intermediate term 5–10 years, and long term 10–20 years.
2The exposure biology program is investing in new technologies to assess how environmental exposures, including diet, physical activity, stress, and drug use, contribute to human disease. This includes sensors for chemicals in the environment, new ways to characterize dietary intake, levels of physical activity, responses to psychosocial stress, and measures of the biologic response to these factors at the physiologic and molecular levels (NIEHS 2009).
Providing effective responses to immediate or short-term public-health or ecologic risks requires research on observational methods, data management, and models:
• Identify, improve, and test instruments that can provide real-time tracking of biologic, chemical, and physical stressors to monitor community and occupational exposures to multiple stressors during natural, accidental, or terrorist events or during combat and acts of war.
• Explore, evaluate, and promote the types of targeted population-based exposure studies that can provide information needed to infer the time course of internal and external exposures to high-priority chemicals.
• Develop informatics technologies (software and hardware) that can transform exposure and environmental databases that address different levels of integration (time scales, geographic scales, and population types) into formats that can be easily and routinely linked with population-wide outcome databases (for humans and ecosystems) and linked to source-to-dose modeling platforms to facilitate rapid discovery of new hazards and to enhance preparedness and timely response.
• Identify, test, and deploy extant remote sensing, high-volume personal monitoring techniques, and source-to-dose model-integration tools that can quantify multiple routes of exposure (inhalation, ingestion, and dermal uptake) and obtain results that can, for example, be integrated with emerging methods (such as —omics technologies) for tracking internal exposures.
• Enhance tracking of human exposures to pathogens on the basis of a holistic ecosystem perspective from source through receptor.
Supporting research on health and ecologic effects that addresses past, current, and emerging outcomes:
• Coordinate research with human-health and ecologic-health scientists to identify, collect, and evaluate data that capture internal and external markers of exposure in a format that improves the analysis and modeling of exposure-response relationships and links to high throughput toxicity testing.
• Explore options for using data obtained on individuals and populations through market-based and product-use research to improve exposure information used in epidemiologic studies and in risk assessments.
• Develop methods for addressing data and model uncertainty and evaluate model performance to achieve parsimony in describing and predicting the complex pathways that link sources and stressors to outcomes.
• Improve integration of information on human behavior and activities for predicting, mitigating, and preventing adverse exposures.
• Adapt hybrid designs for field studies to combine individual-level and group-level measurements for single and multiple routes of exposure to provide exposure data of greater resolution in space and time.
Addressing demands for exposure information among communities, governments, and industries with research that is focused, solution-based, and responsive to a broad array of audiences:
• Develop methods to test consumer products and chemicals in premarketing controlled studies to identify stressors that have a high potential for exposure (intake fraction) combined with a potential for toxicity to humans or ecologic receptors.
• Develop and evaluate cost-effective, standardized, non-targeted, and ubiquitous methods for obtaining exposure information to assess trends, disparities among populations (human and ecologic), geographic hot spots, cumulative exposures, and predictors of vulnerability.
• Apply adaptive environmental-management approaches to understand the linkages between adverse exposures in humans and ecosystems better.
• Implement strategies to engage communities, particularly vulnerable or hot-spot communities, in a collaborative process to identify, evaluate, and mitigate exposures.
• Expand research in ways to use exposure science to more effectively regulate environmental risks in natural and human systems, including the built environment.
Exposure science is relevant to the work and mission of many federal agencies. A transagency collaboration for exposure science in the 21st century would accelerate progress in and transform the field.
Tox21 is a collaboration among EPA, the National Institutes of Health (NIH), and recently the Food and Drug Administration (Collins et al. 2008; Schmidt 2009). The collaboration has been extended to include research partners in Europe and Asia. It resulted from the National Research Council recommendations (NRC 2007) that called for a long-range vision for transforming toxicology to meet the demands of the 21st century—not unlike the vision offered in the present report. The primary objective of the Tox21 collaboration was to leverage resources and expertise. It included sharing databases and analytic tools, cataloging critical toxicologic data for key target organs, sponsoring workshops to broaden scientific input into strategy and direction, engaging the international community, and promoting scientific training and outreach. The budget for Tox21 was developed gradually on the basis of the success of the initial research, and the momentum created by this effort influenced research planning and budgetary directions for other organizations, including industry, nongovernmental organizations, and other federal agencies, to bring resources and expand on this collaboration.
The present committee considers that the model used in establishing Tox21 should be extended to exposure science. This would create Exposure21. In addition to the engagement of those stakeholders involved in Tox21, engagement of other federal agencies—such as the US Geological Survey, CDC, the National Oceanic and Atmospheric Administration, the National Science Foundation (NSF), and the National Aeronautics and Space Administration—would promote access to and sharing of data and resources on a broader scale. Including them would provide access to resources for transformative technology innovations, for example, in nanosensors.
The research needs discussed in the report extend to the activities and the mandates of individual agencies, including EPA and NIEHS. The programmatic
activities of these agencies will be improved by embracing new basic and applied exposure-science research. Over time, the results of this research will provide opportunities to demonstrate its value to aligned agencies and will lead to the formation of new partnerships in exposure science. Such collaborative transformations will improve the ability of decision-makers to use the results in risk-management and in risk-prevention programs. Thus, the committee recommends that intramural and extramural programs at the EPA, NIEHS, Department of Defense, and other agencies that advance exposure-science research be supported, as the value of the research and the need for exposure information become more apparent.
Much of the human-based research in environmental-health sciences is funded by NIH. However, none of the existing study sections that review grant applications has substantial expertise in exposure science and most study sections are organized around disease processes. As part of stakeholder engagement in its 2011 strategic review process, NIEHS identified exposure science as a subject of high research priority (NIEHS 2011a). In light of this new emphasis and the role that an understanding of environmental exposures can play in disease prevention, a rethinking of how NIH study sections are organized that incorporates a greater focus on exposure science would allow a core group of experts to foster the objectives of exposure-science research. In addition, research collaborations between agencies could leverage resources for expanded exposure-science research; for example, collaborations among EPA, NIEHS, and NSF could support integrative research between ecosystem and human-health approaches in exposure science. However, many other agencies engaged in exposure science research could be included in the collaborations.
An additional concern is the need to educate the next generation of exposure scientists or to provide opportunities for members of other fields to cross-train in the techniques and models used to analyze and collect exposure data. The effective implementation of the committee’s vision will depend on development and cultivation of scientists, engineers, and technical experts. For years, academic institutions have mostly trained exposure scientists on the periphery of other programs, such as industrial hygiene and epidemiology. To implement the vision, a new crop of transdisciplinary scientists will need to be trained with integrated expertise in many fields of science, technology, and environmental health, with a focus on problem formulation and solution-based approaches. Exposure scientists will need the skills to collaborate closely with other fields of expertise, including engineers, epidemiologists, molecular and systems biologists, clinicians, statisticians, and social scientists. To achieve that, the committee considers that the following is needed
• An increase in the number of academic predoctoral and postdoctoral training programs in exposure science throughout the United States supported by training grants. NIEHS currently funds one training grant in exposure science; additional training grants are needed (NIEHS 2011b).
• Short-term training and certification programs in exposure science for midcareer scientists in related fields.
• Development, by federal agencies that support human and environmental exposure science, of educational programs to improve public understanding of exposure-assessment research. The programs would need to engage members of the general public, specialists in research oversight, and specific communities that are disproportionately burdened by known environmental stressors.
Participatory and Community-Based Research Programs
Responsiveness as articulated in the committee’s vision involves engaging broader audiences, including the public, in ways that contribute to problem formulation, monitoring and collection of data, ensuring access to data, development of decision-making tools, and ultimately empowerment of communities to participate in reducing and preventing exposures and addressing environmental disparities. The development of more user-friendly and less expensive monitoring equipment can allow trained people in communities to collect and upload their own data in partnership with researchers and thereby improve the value of the data collected and make more data available for purposes of priority-setting and to inform policy. One approach would be to develop pilot programs in which the communities in two large American cities are engaged in implementing a system of embedded and participatory sensors based on ubiquitous and pervasive technologies. The pilot programs would evaluate the feasibility of such systems to develop community-based exposure data that are reliable and the ability of communities to use the data to understand and improve their environmental health. Potential issues of privacy would need to be considered. Examples of such efforts are described in Chapter 5.
The field of exposure science in environmental health began to grow from its roots in occupational health during the early 1990s with the publication of the first National Research Council report on exposure, the formation of a professional society and a journal devoted primarily to exposure science, and the publication of a number of manuscripts on the field’s pivotal role in the environmental-health sciences. The committee has illustrated numerous successes in addressing environmental-health problems and shown the evolution of new tools to address current problems. The critical nature of the field illustrated in Figure 1-2 shows the centrality of efforts to mitigate the effects of sources and to intervene or prevent disease. However, as shown in the committee’s vision (Chapter 2), there is still much work to do to mitigate the potential and actual effects of stressors on humans and ecosystems (for example, nanoparticles, energy sys-
tems and sources, and consumer products). Tools are evolving to determine internal and external exposures, to examine the behaviors that lead to contact, and to characterize stressors before adverse effects occur. With focus, good science, and sustained support for research and development, exposure science will have a bright future.
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