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Exposure to polychlorinated biphenyls (PCBs) can occur through multiple routes and sources, including dietary intake, inhalation, dermal contact, and ingestion of dust and soils. Dietary exposure to PCBs is often considered the primary exposure route for the general population; however, recent studies suggest an increasing contribution from indoor inhalation exposure. Here, we aim to estimate the relative contribution of different PCB exposure pathways for the general population, as well as for select age groups. We conducted a targeted literature review of PCB concentrations in environmental media, including indoor and outdoor air, indoor dust, and soils, as well as of total dietary intake. Using the average concentrations from the studies identified, we estimated PCB exposure through different routes for the general population. In addition, we assessed exposure via environmental media for select age groups. We identified a total of 70 studies, 64 that provided background PCB concentrations for one or more of the environmental media of interest and 6 studies that provided estimates of dietary intake. Using estimates from studies conducted worldwide, for the general population, dietary intake of PCBs was the major exposure pathway. In general, our review identifies important limitations in the data available to assess population exposures, highlighting the need for more current and population-based estimates of PCB exposure, particularly for indoor air and dietary intake.
Chelsea A. Weitekamp; Linda J. Phillips; Laura M. Carlson; Nicole M. DeLuca; Elaine A. Cohen Hubal; Geniece M. Lehmann. A state-of-the-science review of polychlorinated biphenyl exposures at background levels: Relative contributions of exposure routes. Science of The Total Environment 2021, 776, 145912 .
AMA StyleChelsea A. Weitekamp, Linda J. Phillips, Laura M. Carlson, Nicole M. DeLuca, Elaine A. Cohen Hubal, Geniece M. Lehmann. A state-of-the-science review of polychlorinated biphenyl exposures at background levels: Relative contributions of exposure routes. Science of The Total Environment. 2021; 776 ():145912.
Chicago/Turabian StyleChelsea A. Weitekamp; Linda J. Phillips; Laura M. Carlson; Nicole M. DeLuca; Elaine A. Cohen Hubal; Geniece M. Lehmann. 2021. "A state-of-the-science review of polychlorinated biphenyl exposures at background levels: Relative contributions of exposure routes." Science of The Total Environment 776, no. : 145912.
Increasing numbers of chemicals are on the market and present in consumer products. Emerging evidence on the relationship between environmental contributions and prevalent diseases suggests associations between early-life exposure to manufactured chemicals and a wide range of children’s health outcomes. Using current assessment methodologies, public health and chemical management decisionmakers face challenges in evaluating and anticipating the potential impacts of exposure to chemicals on children’s health in the broader context of their physical (built and natural) and social environments. Here, we consider a systems approach to address the complexity of children’s environmental health and the role of exposure to chemicals during early life, in the context of nonchemical stressors, on health outcomes. By advancing the tools for integrating this more complex information, the scope of considerations that support chemical management decisions can be extended to include holistic impacts on children’s health.
Elaine A. Cohen Hubal; David M. Reif; Rachel Slover; Ashley Mullikin; John C. Little. Children’s Environmental Health: A Systems Approach for Anticipating Impacts from Chemicals. International Journal of Environmental Research and Public Health 2020, 17, 8337 .
AMA StyleElaine A. Cohen Hubal, David M. Reif, Rachel Slover, Ashley Mullikin, John C. Little. Children’s Environmental Health: A Systems Approach for Anticipating Impacts from Chemicals. International Journal of Environmental Research and Public Health. 2020; 17 (22):8337.
Chicago/Turabian StyleElaine A. Cohen Hubal; David M. Reif; Rachel Slover; Ashley Mullikin; John C. Little. 2020. "Children’s Environmental Health: A Systems Approach for Anticipating Impacts from Chemicals." International Journal of Environmental Research and Public Health 17, no. 22: 8337.
Systematic review (SR) is a rigorous methodology applied to synthesize and evaluate a body of scientific evidence to answer a research or policy question. Effective use of systematic-review methodology enables use of research evidence by decision makers. In addition, as reliance on systematic reviews increases, the required standards for quality of evidence enhances the policy relevance of research. Authoritative guidance has been developed for use of SR to evaluate evidence in the fields of medicine, social science, environmental epidemiology, toxicology, as well as ecology and evolutionary biology. In these fields, SR is typically used to evaluate a cause–effect relationship, such as the effect of an intervention, procedure, therapy, or exposure on an outcome. However, SR is emerging to be a useful methodology to transparently review and integrate evidence for a wider range of scientifically informed decisions and actions across disciplines. As SR is being used more broadly, there is growing consensus for developing resources, guidelines, ontologies, and technology to make SR more efficient and transparent, especially for handling large amounts of diverse data being generated across multiple scientific disciplines. In this article, we advocate for advancing SR methodology as a best practice in the field of exposure science to synthesize exposure evidence and enhance the value of exposure studies. We discuss available standards and tools that can be applied and extended by exposure scientists and highlight early examples of SRs being developed to address exposure research questions. Finally, we invite the exposure science community to engage in further development of standards and guidance to grow application of SR in this field and expand the opportunities for exposure science to inform environment and public health decision making.
Elaine A. Cohen Hubal; Jessica J. Frank; Rebecca Nachman; Michelle Angrish; Nicole C. DeZiel; Meridith Fry; Rogelio Tornero-Velez; Andrew Kraft; Emma Lavoie. Advancing systematic-review methodology in exposure science for environmental health decision making. Journal of Exposure Science & Environmental Epidemiology 2020, 30, 906 -916.
AMA StyleElaine A. Cohen Hubal, Jessica J. Frank, Rebecca Nachman, Michelle Angrish, Nicole C. DeZiel, Meridith Fry, Rogelio Tornero-Velez, Andrew Kraft, Emma Lavoie. Advancing systematic-review methodology in exposure science for environmental health decision making. Journal of Exposure Science & Environmental Epidemiology. 2020; 30 (6):906-916.
Chicago/Turabian StyleElaine A. Cohen Hubal; Jessica J. Frank; Rebecca Nachman; Michelle Angrish; Nicole C. DeZiel; Meridith Fry; Rogelio Tornero-Velez; Andrew Kraft; Emma Lavoie. 2020. "Advancing systematic-review methodology in exposure science for environmental health decision making." Journal of Exposure Science & Environmental Epidemiology 30, no. 6: 906-916.
Scientifically sound, risk-informed evaluation of chemicals is essential to protecting public health. Systematically leveraging information from exposure, toxicology, and epidemiology studies can provide a holistic understanding of how real-world exposure to chemicals may impact the health of populations, including sensitive and vulnerable individuals and life-stages. Increasingly, public health policy makers are employing toxicokinetic (TK) modeling tools to integrate these data streams and predict potential human health impact. Development of a suite of tools for predicting internal exposure, including physiologically-based toxicokinetic (PBTK) models, is being driven by needs to address large numbers of data-poor chemicals efficiently, translate bioactivity, and mechanistic information from new in vitro test systems, and integrate multiple lines of evidence to enable scientifically sound, risk-informed decisions. New modeling approaches are being designed “fit for purpose” to inform specific decision contexts, with applications ranging from rapid screening of hundreds of chemicals, to improved prediction of risks during sensitive stages of development. New data are being generated experimentally and computationally to support these models. Progress to meet the demand for internal exposure and PBTK modeling tools will require transparent publication of models and data to build credibility in results, as well as opportunities to partner with decision makers to evaluate and build confidence in use of these for improved decisions that promote safe use of chemicals.
Elaine A. Cohen Hubal; Barbara A. Wetmore; John Wambaugh; Hisham El-Masri; Jon Sobus; Tina Bahadori. Advancing internal exposure and physiologically-based toxicokinetic modeling for 21st-century risk assessments. Journal of Exposure Science & Environmental Epidemiology 2018, 29, 11 -20.
AMA StyleElaine A. Cohen Hubal, Barbara A. Wetmore, John Wambaugh, Hisham El-Masri, Jon Sobus, Tina Bahadori. Advancing internal exposure and physiologically-based toxicokinetic modeling for 21st-century risk assessments. Journal of Exposure Science & Environmental Epidemiology. 2018; 29 (1):11-20.
Chicago/Turabian StyleElaine A. Cohen Hubal; Barbara A. Wetmore; John Wambaugh; Hisham El-Masri; Jon Sobus; Tina Bahadori. 2018. "Advancing internal exposure and physiologically-based toxicokinetic modeling for 21st-century risk assessments." Journal of Exposure Science & Environmental Epidemiology 29, no. 1: 11-20.
Engineered nanomaterials (ENM) are a growing aspect of the global economy, and their safe and sustainable development, use, and eventual disposal requires the capability to forecast and avoid potential problems. This review provides a framework to evaluate the health and safety implications of ENM releases into the environment, including purposeful releases such as for antimicrobial sprays or nano-enabled pesticides, and inadvertent releases as a consequence of other intended applications. Considerations encompass product life cycles, environmental media, exposed populations, and possible adverse outcomes. This framework is presented as a series of compartmental flow diagrams that serve as a basis to help derive future quantitative predictive models, guide research, and support development of tools for making risk-based decisions. After use, ENM are not expected to remain in their original form due to reactivity and/or propensity for hetero-agglomeration in environmental media. Therefore, emphasis is placed on characterizing ENM as they occur in environmental or biological matrices. In addition, predicting the activity of ENM in the environment is difficult due to the multiple dynamic interactions between the physical/chemical aspects of ENM and similarly complex environmental conditions. Others have proposed the use of simple predictive functional assays as an intermediate step to address the challenge of using physical/chemical properties to predict environmental fate and behavior of ENM. The nodes and interactions of the framework presented here reflect phase transitions that could be targets for development of such assays to estimate kinetic reaction rates and simplify model predictions. Application, refinement, and demonstration of this framework, along with an associated knowledgebase that includes targeted functional assay data, will allow better de novo predictions of potential exposures and adverse outcomes.
William K. Boyes; Brittany Lila Thornton; Souhail R. Al-Abed; Christian P. Andersen; Dermont C. Bouchard; Robert M. Burgess; Elaine A. Cohen Hubal; Kay T. Ho; Michael F. Hughes; Kirk Kitchin; Jay R. Reichman; Kim R. Rogers; Jeffrey A. Ross; Paul T. Rygiewicz; Kirk G. Scheckel; Sheau-Fung Thai; Richard G. Zepp; Robert M. Zucker. A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials. Critical Reviews in Toxicology 2017, 47, 771 -814.
AMA StyleWilliam K. Boyes, Brittany Lila Thornton, Souhail R. Al-Abed, Christian P. Andersen, Dermont C. Bouchard, Robert M. Burgess, Elaine A. Cohen Hubal, Kay T. Ho, Michael F. Hughes, Kirk Kitchin, Jay R. Reichman, Kim R. Rogers, Jeffrey A. Ross, Paul T. Rygiewicz, Kirk G. Scheckel, Sheau-Fung Thai, Richard G. Zepp, Robert M. Zucker. A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials. Critical Reviews in Toxicology. 2017; 47 (9):771-814.
Chicago/Turabian StyleWilliam K. Boyes; Brittany Lila Thornton; Souhail R. Al-Abed; Christian P. Andersen; Dermont C. Bouchard; Robert M. Burgess; Elaine A. Cohen Hubal; Kay T. Ho; Michael F. Hughes; Kirk Kitchin; Jay R. Reichman; Kim R. Rogers; Jeffrey A. Ross; Paul T. Rygiewicz; Kirk G. Scheckel; Sheau-Fung Thai; Richard G. Zepp; Robert M. Zucker. 2017. "A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials." Critical Reviews in Toxicology 47, no. 9: 771-814.
Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations—where observing outcomes is difficult—versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test endpoints, duration, and study conditions—including ENM test concentrations—that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.
Patricia A. Holden; Jorge L. Gardea-Torresdey; Fred Klaessig; Ronald F. Turco; Monika Mortimer; Kerstin Hund-Rinke; Elaine A. Cohen Hubal; David Avery; Damià Barceló; Renata Behra; Yoram Cohen; Laurence Deydier-Stephan; Patrick Lee Ferguson; Teresa F. Fernandes; Barbara Herr Harthorn; William Matthew Henderson; Robert A. Hoke; Danail Hristozov; John M. Johnston; Agnes B. Kane; Larry Kapustka; Arturo A. Keller; Hunter S. Lenihan; Wess Lovell; Catherine J. Murphy; Roger M. Nisbet; Elijah J. Petersen; Edward R. Salinas; Martin Scheringer; Monita Sharma; David E. Speed; Yasir Sultan; Paul Westerhoff; Jason C. White; Mark R. Wiesner; Eva M. Wong; Baoshan Xing; Meghan Steele Horan; Hilary A. Godwin; André E. Nel. Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials. Environmental Science & Technology 2016, 50, 6124 -6145.
AMA StylePatricia A. Holden, Jorge L. Gardea-Torresdey, Fred Klaessig, Ronald F. Turco, Monika Mortimer, Kerstin Hund-Rinke, Elaine A. Cohen Hubal, David Avery, Damià Barceló, Renata Behra, Yoram Cohen, Laurence Deydier-Stephan, Patrick Lee Ferguson, Teresa F. Fernandes, Barbara Herr Harthorn, William Matthew Henderson, Robert A. Hoke, Danail Hristozov, John M. Johnston, Agnes B. Kane, Larry Kapustka, Arturo A. Keller, Hunter S. Lenihan, Wess Lovell, Catherine J. Murphy, Roger M. Nisbet, Elijah J. Petersen, Edward R. Salinas, Martin Scheringer, Monita Sharma, David E. Speed, Yasir Sultan, Paul Westerhoff, Jason C. White, Mark R. Wiesner, Eva M. Wong, Baoshan Xing, Meghan Steele Horan, Hilary A. Godwin, André E. Nel. Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials. Environmental Science & Technology. 2016; 50 (12):6124-6145.
Chicago/Turabian StylePatricia A. Holden; Jorge L. Gardea-Torresdey; Fred Klaessig; Ronald F. Turco; Monika Mortimer; Kerstin Hund-Rinke; Elaine A. Cohen Hubal; David Avery; Damià Barceló; Renata Behra; Yoram Cohen; Laurence Deydier-Stephan; Patrick Lee Ferguson; Teresa F. Fernandes; Barbara Herr Harthorn; William Matthew Henderson; Robert A. Hoke; Danail Hristozov; John M. Johnston; Agnes B. Kane; Larry Kapustka; Arturo A. Keller; Hunter S. Lenihan; Wess Lovell; Catherine J. Murphy; Roger M. Nisbet; Elijah J. Petersen; Edward R. Salinas; Martin Scheringer; Monita Sharma; David E. Speed; Yasir Sultan; Paul Westerhoff; Jason C. White; Mark R. Wiesner; Eva M. Wong; Baoshan Xing; Meghan Steele Horan; Hilary A. Godwin; André E. Nel. 2016. "Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials." Environmental Science & Technology 50, no. 12: 6124-6145.
While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA's need to develop novel approaches and tools for rapidly prioritizing chemicals, a “Challenge” was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA's effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches.
Jade Mitchell; Jon A. Arnot; Olivier Jolliet; Panos G. Georgopoulos; Sastry Isukapalli; Surajit Dasgupta; Muhilan Pandian; John Wambaugh; Peter Egeghy; Elaine A. Cohen Hubal; Daniel A. Vallero. Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential. Science of The Total Environment 2013, 458-460, 555 -567.
AMA StyleJade Mitchell, Jon A. Arnot, Olivier Jolliet, Panos G. Georgopoulos, Sastry Isukapalli, Surajit Dasgupta, Muhilan Pandian, John Wambaugh, Peter Egeghy, Elaine A. Cohen Hubal, Daniel A. Vallero. Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential. Science of The Total Environment. 2013; 458-460 ():555-567.
Chicago/Turabian StyleJade Mitchell; Jon A. Arnot; Olivier Jolliet; Panos G. Georgopoulos; Sastry Isukapalli; Surajit Dasgupta; Muhilan Pandian; John Wambaugh; Peter Egeghy; Elaine A. Cohen Hubal; Daniel A. Vallero. 2013. "Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential." Science of The Total Environment 458-460, no. : 555-567.
Waste and materials management, land use planning, transportation and infrastructure including water and energy can have indirect or direct beneficial impacts on the environment and public health. The potential for impact, however, is rarely viewed in an integrated fashion. To facilitate such an integrated view in support of community-based policy decision making, we catalogued and evaluated associations between common, publically available, Environmental (e), Health (h), and Sustainability (s) metrics and sociodemographic measurements (n = 10) for 50 populous U.S. cities. E, H, S indices combined from two sources were derived from component (e) (h) (s) metrics for each city. A composite EHS Index was derived to reflect the integration across the E, H, and S indices. Rank order of high performing cities was highly dependent on the E, H and S indices considered. When viewed together with sociodemographic measurements, our analyses further the understanding of the interplay between these broad categories and reveal significant sociodemographic disparities (e.g., race, education, income) associated with low performing cities. Our analyses demonstrate how publically available environmental, health, sustainability and socioeconomic data sets can be used to better understand interconnections between these diverse domains for more holistic community assessments.
Jane E. Gallagher; Elaine Cohen Hubal; Laura Jackson; Jefferson Inmon; Edward Hudgens; Ann H. Williams; Danelle Lobdell; John Rogers; Timothy Wade. Sustainability, Health and Environmental Metrics: Impact on Ranking and Associations with Socioeconomic Measures for 50 U.S. Cities. Sustainability 2013, 5, 789 -804.
AMA StyleJane E. Gallagher, Elaine Cohen Hubal, Laura Jackson, Jefferson Inmon, Edward Hudgens, Ann H. Williams, Danelle Lobdell, John Rogers, Timothy Wade. Sustainability, Health and Environmental Metrics: Impact on Ranking and Associations with Socioeconomic Measures for 50 U.S. Cities. Sustainability. 2013; 5 (2):789-804.
Chicago/Turabian StyleJane E. Gallagher; Elaine Cohen Hubal; Laura Jackson; Jefferson Inmon; Edward Hudgens; Ann H. Williams; Danelle Lobdell; John Rogers; Timothy Wade. 2013. "Sustainability, Health and Environmental Metrics: Impact on Ranking and Associations with Socioeconomic Measures for 50 U.S. Cities." Sustainability 5, no. 2: 789-804.
Complex diseases are often difficult to diagnose, treat and study due to the multi-factorial nature of the underlying etiology. Large data sets are now widely available that can be used to define novel, mechanistically distinct disease subtypes (endotypes) in a completely data-driven manner. However, significant challenges exist with regard to how to segregate individuals into suitable subtypes of the disease and understand the distinct biological mechanisms of each when the goal is to maximize the discovery potential of these data sets.
ClarLynda R Williams-DeVane; David M Reif; Elaine Cohen Hubal; Pierre R Bushel; Edward E Hudgens; Jane E Gallagher; Stephen W Edwards. Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes. BMC Systems Biology 2013, 7, 119 -119.
AMA StyleClarLynda R Williams-DeVane, David M Reif, Elaine Cohen Hubal, Pierre R Bushel, Edward E Hudgens, Jane E Gallagher, Stephen W Edwards. Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes. BMC Systems Biology. 2013; 7 (1):119-119.
Chicago/Turabian StyleClarLynda R Williams-DeVane; David M Reif; Elaine Cohen Hubal; Pierre R Bushel; Edward E Hudgens; Jane E Gallagher; Stephen W Edwards. 2013. "Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes." BMC Systems Biology 7, no. 1: 119-119.
The Toxicological Prioritization Index (ToxPi) decision support framework was previously developed to facilitate incorporation of diverse data to prioritize chemicals based on potential hazard. This ToxPi index was demonstrated by considering results of bioprofiling related to potential for endocrine disruption. However, exposure information is required along with hazard information to prioritize chemicals for further testing. The goal of this analysis is to demonstrate the utility of the ToxPi framework for incorporating exposure information to rank chemicals and improve understanding of key exposure surrogates. The ToxPi tool was applied to common exposure surrogates (i.e., fate parameters, manufacturing volume, and occurrence measurements) and the relationship between resulting rankings and higher-tiered exposure estimates was investigated. As information more directly relevant to human exposure potential is incorporated, relative rank of chemicals changes. Binned ToxPi results are shown to be consistent with chemical priorities based on crude measures of population-level exposure for a limited set of chemicals. However, these bins are not predictive of higher tiered estimates of exposure such as those developed for pesticide registration. Although rankings based on exposure surrogates are used in a variety of contexts, analysis of the relevance of these tools is challenging. The ToxPi framework can be used to gain insight into the factors driving these rankings and aid identification of key exposure metrics. Additional exposure data is required to build confidence in exposure-based chemical prioritization.
Sumit Gangwal; David M. Reif; Shad Mosher; Peter P. Egeghy; John F. Wambaugh; Richard S. Judson; Elaine A. Cohen Hubal. Incorporating exposure information into the toxicological prioritization index decision support framework. Science of The Total Environment 2012, 435-436, 316 -325.
AMA StyleSumit Gangwal, David M. Reif, Shad Mosher, Peter P. Egeghy, John F. Wambaugh, Richard S. Judson, Elaine A. Cohen Hubal. Incorporating exposure information into the toxicological prioritization index decision support framework. Science of The Total Environment. 2012; 435-436 ():316-325.
Chicago/Turabian StyleSumit Gangwal; David M. Reif; Shad Mosher; Peter P. Egeghy; John F. Wambaugh; Richard S. Judson; Elaine A. Cohen Hubal. 2012. "Incorporating exposure information into the toxicological prioritization index decision support framework." Science of The Total Environment 435-436, no. : 316-325.
Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.
Richard S. Judson; Matthew T. Martin; Peter Egeghy; Sumit Gangwal; David M. Reif; Parth Kothiya; Maritja Wolf; Tommy Cathey; Thomas Transue; Doris Smith; James Vail; Alicia Frame; Shad Mosher; Elaine A. Cohen Hubal; Ann M. Richard. Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System. International Journal of Molecular Sciences 2012, 13, 1805 -1831.
AMA StyleRichard S. Judson, Matthew T. Martin, Peter Egeghy, Sumit Gangwal, David M. Reif, Parth Kothiya, Maritja Wolf, Tommy Cathey, Thomas Transue, Doris Smith, James Vail, Alicia Frame, Shad Mosher, Elaine A. Cohen Hubal, Ann M. Richard. Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System. International Journal of Molecular Sciences. 2012; 13 (2):1805-1831.
Chicago/Turabian StyleRichard S. Judson; Matthew T. Martin; Peter Egeghy; Sumit Gangwal; David M. Reif; Parth Kothiya; Maritja Wolf; Tommy Cathey; Thomas Transue; Doris Smith; James Vail; Alicia Frame; Shad Mosher; Elaine A. Cohen Hubal; Ann M. Richard. 2012. "Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System." International Journal of Molecular Sciences 13, no. 2: 1805-1831.
The U.S. Environmental Protection Agency is developing chemical screening and prioritization programs to evaluate environmental chemicals for potential risk to human health in a rapid and efficient manner. As part of these efforts, it is important to catalog available information on chemical toxicity and exposure from widely dispersed sources. The main objective of this analysis is to define important aspects of the exposure space and to catalog the available exposure information for chemicals being considered for analysis as part of the U.S. EPA ToxCast™ screening and prioritization program. Publicly available exposure data have been extracted into ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from >600 public sources. We use data from ACToR to assess the exposure data landscape for environmental chemicals. Of the roughly 100,000 chemicals that have at least limited toxicity information available, less than one-fifth also have exposure information - and for most of these the information is of limited utility (e.g., production volume). Readily accessible data on concentrations in exposure-related media are only available for a much smaller fraction. Among these, the largest number of chemicals is measured in water with over 1150 unique compounds, followed by 788 substances measured in soil, and 670 in air. These small numbers clearly reflect a focus of resources on those substances previously identified as possibly posing a hazard to human health. Exposure to a much broader number of chemicals will need to be measured in order to fully realize the envisioned goal of using exposure information to guide toxicity testing.
Peter P. Egeghy; Richard Judson; Sumit Gangwal; Shad Mosher; Doris Smith; James Vail; Elaine A. Cohen Hubal. The exposure data landscape for manufactured chemicals. Science of The Total Environment 2012, 414, 159 -166.
AMA StylePeter P. Egeghy, Richard Judson, Sumit Gangwal, Shad Mosher, Doris Smith, James Vail, Elaine A. Cohen Hubal. The exposure data landscape for manufactured chemicals. Science of The Total Environment. 2012; 414 ():159-166.
Chicago/Turabian StylePeter P. Egeghy; Richard Judson; Sumit Gangwal; Shad Mosher; Doris Smith; James Vail; Elaine A. Cohen Hubal. 2012. "The exposure data landscape for manufactured chemicals." Science of The Total Environment 414, no. : 159-166.
Health, socioeconomic, education, and environmental (e.g. air and water quality) indicators are often correlated and may serve as markers for other underlying community issues. These diverse measurements are usually not fully integrated and rarely evaluated in the context of sustainability metrics. We derived an integrated community health index (ICHI) for 50 of the most populous cities in the US using extant environmental, health and sustainability metrics and assessed relationships with sociodemographic measures. To derive the ICHI we used data from two sources: 1) SustainLane\'s (www.sustainlane.com) 2008 report card on urban sustainability which includes metrics such as energy and climate change policy, metro street congestion, metro transit ridership, and natural disaster risk, and 2) Earth Day Network\'s (www.eathday.net) Urban environmental report including a health metric which incorporates asthma, cardiovascular disease, diabetes, and obesity rates; and three environmental variables a) toxics and waste b) air quality c) drinking and surface water quality. Using these metrics we developed three separate indicators for health, sustainability and environment for each city. The ICHI was created by averaging across these three indicators. We used data from the 2010 Census (median family income, % of persons below the poverty level, % with a high school degree, % with college degree, and racial diversity (% White, nonwhite Black, Asian, and Hispanic) to assess relationships between the ICHI and sociodemographic characteristics. We compare mean values for various demographic measures for those cities with the "best" integrated community health index (highest 25th percentile) with those cities in the lower 25th percentile using t-tests. Cities with the better ICHI demonstrated 1) a higher % of persons with health insurance (20.1 vs 13.4 %; pth percentile) with those cities in the lowest 25thpercentile demonstrated 1) a lower score for toxic and waste (2.85 vs. 3.48; p
Jane Gallagher; Timothy Wade; Laura Jackson; Danelle Lobdell; Jyotsna Jagai; Jefferson Inmon; Elaine Cohen-Hubal. Correlates of Health, Sustainability and Environmental Metrics for 50 of the Most Populous U.S. Cities. Proceedings of The 1st World Sustainability Forum 2011, 1 .
AMA StyleJane Gallagher, Timothy Wade, Laura Jackson, Danelle Lobdell, Jyotsna Jagai, Jefferson Inmon, Elaine Cohen-Hubal. Correlates of Health, Sustainability and Environmental Metrics for 50 of the Most Populous U.S. Cities. Proceedings of The 1st World Sustainability Forum. 2011; ():1.
Chicago/Turabian StyleJane Gallagher; Timothy Wade; Laura Jackson; Danelle Lobdell; Jyotsna Jagai; Jefferson Inmon; Elaine Cohen-Hubal. 2011. "Correlates of Health, Sustainability and Environmental Metrics for 50 of the Most Populous U.S. Cities." Proceedings of The 1st World Sustainability Forum , no. : 1.
A challenge with multiple chemical risk assessment is the need to consider the joint behavior of chemicals in mixtures. To address this need, pharmacologists and toxicologists have developed methods over the years to evaluate and test chemical interaction. In practice, however, testing of chemical interaction more often comprises ad hoc binary combinations and rarely examines higher order combinations. One explanation for this practice is the belief that there are simply too many possible combinations of chemicals to consider. Indeed, under stochastic conditions the possible number of chemical combinations scales geometrically as the pool of chemicals increases. However, the occurrence of chemicals in the environment is determined by factors, economic in part, which favor some chemicals over others. We investigate methods from the field of biogeography, originally developed to study avian species co-occurrence patterns, and adapt these approaches to examine chemical co-occurrence. These methods were applied to a national survey of pesticide residues in 168 child care centers from across the country. Our findings show that pesticide co-occurrence in the child care center was not random but highly structured, leading to the co-occurrence of specific pesticide combinations. Thus, ecological studies of species co-occurrence parallel the issue of chemical co-occurrence at specific locations. Both are driven by processes that introduce structure in the pattern of co-occurrence. We conclude that the biogeographical tools used to determine when this structure occurs in ecological studies are relevant to evaluations of pesticide mixtures for exposure and risk assessment.
Rogelio Tornero‐Velez; Peter P. Egeghy; Elaine A. Cohen Hubal. Biogeographical Analysis of Chemical Co-Occurrence Data to Identify Priorities for Mixtures Research. Risk Analysis 2011, 32, 224 -236.
AMA StyleRogelio Tornero‐Velez, Peter P. Egeghy, Elaine A. Cohen Hubal. Biogeographical Analysis of Chemical Co-Occurrence Data to Identify Priorities for Mixtures Research. Risk Analysis. 2011; 32 (2):224-236.
Chicago/Turabian StyleRogelio Tornero‐Velez; Peter P. Egeghy; Elaine A. Cohen Hubal. 2011. "Biogeographical Analysis of Chemical Co-Occurrence Data to Identify Priorities for Mixtures Research." Risk Analysis 32, no. 2: 224-236.
Children are exposed to a wide variety of pesticides originating from both outdoor and indoor sources. Several studies were conducted or funded by the EPA over the past decade to investigate children’s exposure to organophosphate and pyrethroid pesticides and the factors that impact their exposures. Urinary metabolite concentration measurements from these studies are consolidated here to identify trends, spatial and temporal patterns, and areas where further research is required. Namely, concentrations of the metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol or TCPy), diazinon (2-isopropyl-6-methyl-4-pyrimidinol or IMP), and permethrin (3-phenoxybenzoic acid or 3-PBA) are presented. Information on the kinetic parameters describing absorption and elimination in humans is also presented to aid in interpretation. Metabolite concentrations varied more dramatically across studies for 3-PBA and IMP than for TCPy, with TCPy concentrations about an order of magnitude higher than the 3-PBA concentrations. Temporal variability was high for all metabolites with urinary 3-PBA concentrations slightly more consistent over time than the TCPy concentrations. Urinary biomarker levels provided only limited evidence of applications. The observed relationships between urinary metabolite levels and estimates of pesticide intake may be affected by differences in the contribution of each exposure route to total intake, which may vary with exposure intensity and across individuals.
Peter P. Egeghy; Elaine A. Cohen Hubal; Nicolle S. Tulve; Lisa J. Melnyk; Marsha K. Morgan; Roy C. Fortmann; Linda S. Sheldon. Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies. International Journal of Environmental Research and Public Health 2011, 8, 1727 -1754.
AMA StylePeter P. Egeghy, Elaine A. Cohen Hubal, Nicolle S. Tulve, Lisa J. Melnyk, Marsha K. Morgan, Roy C. Fortmann, Linda S. Sheldon. Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies. International Journal of Environmental Research and Public Health. 2011; 8 (5):1727-1754.
Chicago/Turabian StylePeter P. Egeghy; Elaine A. Cohen Hubal; Nicolle S. Tulve; Lisa J. Melnyk; Marsha K. Morgan; Roy C. Fortmann; Linda S. Sheldon. 2011. "Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies." International Journal of Environmental Research and Public Health 8, no. 5: 1727-1754.
Asthma is a common complex disease responsible for considerable morbidity and mortality, particularly in urban minority populations. The Mechanistic Indicators of Childhood Asthma study was designed to pilot an integrative approach in children's health research. The study incorporates exposure metrics, internal dose measures, and clinical indicators to decipher the biological complexity inherent in diseases such as asthma and cardiovascular disease with etiology related to gene-environment interactions.
Jane Gallagher; Edward Hudgens; Ann Williams; Jefferson Inmon; Scott Rhoney; Gina Andrews; David Reif; Brooke Heidenfelder; Lucas Neas; Ronald Williams; Markey Johnson; Haluk Özkaynak; Stephen Edwards; Elaine Cohen Hubal. Mechanistic Indicators of Childhood Asthma (MICA) Study: piloting an integrative design for evaluating environmental health. BMC Public Health 2011, 11, 344 -344.
AMA StyleJane Gallagher, Edward Hudgens, Ann Williams, Jefferson Inmon, Scott Rhoney, Gina Andrews, David Reif, Brooke Heidenfelder, Lucas Neas, Ronald Williams, Markey Johnson, Haluk Özkaynak, Stephen Edwards, Elaine Cohen Hubal. Mechanistic Indicators of Childhood Asthma (MICA) Study: piloting an integrative design for evaluating environmental health. BMC Public Health. 2011; 11 (1):344-344.
Chicago/Turabian StyleJane Gallagher; Edward Hudgens; Ann Williams; Jefferson Inmon; Scott Rhoney; Gina Andrews; David Reif; Brooke Heidenfelder; Lucas Neas; Ronald Williams; Markey Johnson; Haluk Özkaynak; Stephen Edwards; Elaine Cohen Hubal. 2011. "Mechanistic Indicators of Childhood Asthma (MICA) Study: piloting an integrative design for evaluating environmental health." BMC Public Health 11, no. 1: 344-344.
Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted.
Bonnie R Joubert; David M Reif; Stephen W Edwards; Kevin A Leiner; Edward E Hudgens; Peter Egeghy; Jane E Gallagher; Elaine Cohen Hubal. Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population. BMC Medical Genetics 2011, 12, 25 -11.
AMA StyleBonnie R Joubert, David M Reif, Stephen W Edwards, Kevin A Leiner, Edward E Hudgens, Peter Egeghy, Jane E Gallagher, Elaine Cohen Hubal. Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population. BMC Medical Genetics. 2011; 12 (1):25-11.
Chicago/Turabian StyleBonnie R Joubert; David M Reif; Stephen W Edwards; Kevin A Leiner; Edward E Hudgens; Peter Egeghy; Jane E Gallagher; Elaine Cohen Hubal. 2011. "Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population." BMC Medical Genetics 12, no. 1: 25-11.
Exposure science is the bedrock for protection of public health. It fundamentally informs decisions that relate to smart and sustainable design, prevention and mitigation of adverse exposures, and ultimately health protection.
Elaine A Cohen Hubal; Dana B Barr; Holger Martin Koch; Tina Bahadori. The Promise of Exposure Science. Journal of Exposure Science & Environmental Epidemiology 2011, 21, 121 -122.
AMA StyleElaine A Cohen Hubal, Dana B Barr, Holger Martin Koch, Tina Bahadori. The Promise of Exposure Science. Journal of Exposure Science & Environmental Epidemiology. 2011; 21 (2):121-122.
Chicago/Turabian StyleElaine A Cohen Hubal; Dana B Barr; Holger Martin Koch; Tina Bahadori. 2011. "The Promise of Exposure Science." Journal of Exposure Science & Environmental Epidemiology 21, no. 2: 121-122.
A new generation of scientific tools has emerged to rapidly measure signals from cells, tissues, and organisms following exposure to chemicals. High-visibility efforts to apply these tools for efficient toxicity testing raise important research questions in exposure science. As vast quantities of data from high-throughput screening (HTS) in vitro toxicity assays become available, this new toxicity information must be translated to assess potential risks to human health from environmental exposures. Exposure information is required to link information on potential toxicity of environmental contaminants to real-world health outcomes. In the immediate term, tools are required to characterize and classify thousands of environmental chemicals in a rapid and efficient manner to prioritize testing and assess potential for risk to human health. Rapid risk assessment requires prioritization based on both hazard and exposure dimensions of the problem. To address these immediate needs within the context of longer term objectives for chemical evaluation and risk management, a translation framework is presented for incorporating toxicity and exposure information to inform public health decisions at both the individual and population levels. Examples of required exposure science contributions are presented with a focus on early advances in tools for modeling important links across the source-to-outcome paradigm. ExpoCast, a new U.S. Environmental Protection Agency (EPA) program aimed at developing novel approaches and metrics to screen and evaluate chemicals based on the potential for biologically relevant human exposures is introduced. The goal of ExpoCast is to advance characterization of exposure required to translate findings in computational toxicology to information that can be directly used to support exposure and risk assessment for decision making and improved public health.
Elaine A. Cohen Hubal; Ann Richard; Lesa Aylward; Stephen Edwards; Jane Gallagher; Michael-Rock Goldsmith; Sastry Isukapalli; Rogelio Tornero-Velez; Eric Weber; Robert Kavlock. Advancing Exposure Characterization for Chemical Evaluation and Risk Assessment. Journal of Toxicology and Environmental Health, Part B 2010, 13, 299 -313.
AMA StyleElaine A. Cohen Hubal, Ann Richard, Lesa Aylward, Stephen Edwards, Jane Gallagher, Michael-Rock Goldsmith, Sastry Isukapalli, Rogelio Tornero-Velez, Eric Weber, Robert Kavlock. Advancing Exposure Characterization for Chemical Evaluation and Risk Assessment. Journal of Toxicology and Environmental Health, Part B. 2010; 13 (2-4):299-313.
Chicago/Turabian StyleElaine A. Cohen Hubal; Ann Richard; Lesa Aylward; Stephen Edwards; Jane Gallagher; Michael-Rock Goldsmith; Sastry Isukapalli; Rogelio Tornero-Velez; Eric Weber; Robert Kavlock. 2010. "Advancing Exposure Characterization for Chemical Evaluation and Risk Assessment." Journal of Toxicology and Environmental Health, Part B 13, no. 2-4: 299-313.
High visibility efforts in toxicity testing and computational toxicology including the recent National Research Council of the National Academies (NRC) report, Toxicity Testing in the 21st Century: A Vision and Strategy (NRC, 2007a), raise important research questions and opportunities for the field of exposure science. The authors of the National Academies report (NRC, 2007a) emphasize that population-based data and human exposure information are required at each step of their vision for toxicity testing and that these data will continue to play a critical role in both guiding development and use of the toxicity information. In fact, state-of-the-art exposure science is essential for translation of toxicity data to assess potential for risk to individuals and populations and to inform public health decisions. As we move forward to implement the NRC vision, a transformational change in exposure science is required. Application of a fresh perspective and novel techniques to capture critical determinants at biologically motivated resolution for translation from controlled in vitro systems to the open multifactorial system of real-world human-environment interaction will be critical. Development of an exposure ontology and knowledgebase will facilitate extension of network analysis to the individual and population for translating toxicity information and assessing health risk. Such a sea change in exposure science is required to incorporate consideration of lifestage, genetic susceptibility, and interaction of nonchemical stressors for holistic assessment of risk factors associated with complex environmental disease. A new generation of scientific tools has emerged to rapidly measure signals from cells, tissues, and organisms following exposure to chemicals. Investment in 21st century exposure science is now required to fully realize the potential of the NRC vision for toxicity testing.
Elaine A. Cohen Hubal. Biologically Relevant Exposure Science for 21st Century Toxicity Testing. Toxicological Sciences 2009, 111, 226 -232.
AMA StyleElaine A. Cohen Hubal. Biologically Relevant Exposure Science for 21st Century Toxicity Testing. Toxicological Sciences. 2009; 111 (2):226-232.
Chicago/Turabian StyleElaine A. Cohen Hubal. 2009. "Biologically Relevant Exposure Science for 21st Century Toxicity Testing." Toxicological Sciences 111, no. 2: 226-232.