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      An Overview of Literature Topics Related to Current Concepts, Methods, Tools, and Applications for Cumulative Risk Assessment (2007–2016)

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          Abstract

          Cumulative risk assessments (CRAs) address combined risks from exposures to multiple chemical and nonchemical stressors and may focus on vulnerable communities or populations. Significant contributions have been made to the development of concepts, methods, and applications for CRA over the past decade. Work in both human health and ecological cumulative risk has advanced in two different contexts. The first context is the effects of chemical mixtures that share common modes of action, or that cause common adverse outcomes. In this context two primary models are used for predicting mixture effects, dose addition or response addition. The second context is evaluating the combined effects of chemical and nonchemical (e.g., radiation, biological, nutritional, economic, psychological, habitat alteration, land-use change, global climate change, and natural disasters) stressors. CRA can be adapted to address risk in many contexts, and this adaptability is reflected in the range in disciplinary perspectives in the published literature. This article presents the results of a literature search and discusses a range of selected work with the intention to give a broad overview of relevant topics and provide a starting point for researchers interested in CRA applications.

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          Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment.

          Gerald Ankley, Richard S. Bennett, Russell Erickson … (2010)
          Ecological risk assessors face increasing demands to assess more chemicals, with greater speed and accuracy, and to do so using fewer resources and experimental animals. New approaches in biological and computational sciences may be able to generate mechanistic information that could help in meeting these challenges. However, to use mechanistic data to support chemical assessments, there is a need for effective translation of this information into endpoints meaningful to ecological risk-effects on survival, development, and reproduction in individual organisms and, by extension, impacts on populations. Here we discuss a framework designed for this purpose, the adverse outcome pathway (AOP). An AOP is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome at a biological level of organization relevant to risk assessment. The practical utility of AOPs for ecological risk assessment of chemicals is illustrated using five case examples. The examples demonstrate how the AOP concept can focus toxicity testing in terms of species and endpoint selection, enhance across-chemical extrapolation, and support prediction of mixture effects. The examples also show how AOPs facilitate use of molecular or biochemical endpoints (sometimes referred to as biomarkers) for forecasting chemical impacts on individuals and populations. In the concluding sections of the paper, we discuss how AOPs can help to guide research that supports chemical risk assessments and advocate for the incorporation of this approach into a broader systems biology framework.
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            Adverse outcome pathway (AOP) development I: strategies and principles.

            Daniel Villeneuve, Doug Crump, Natàlia Garcia-Reyero … (2014)
            An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components-notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development.
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              Interactions between effects of environmental chemicals and natural stressors: a review.

              Martin Holmstrup, Anne-Mette Bindesbøl, Gertie Janneke Oostingh … (2010)
              Ecotoxicological effect studies often expose test organisms under optimal environmental conditions. However, organisms in their natural settings rarely experience optimal conditions. On the contrary, during most of their lifetime they are forced to cope with sub-optimal conditions and occasionally with severe environmental stress. Interactions between the effects of a natural stressor and a toxicant can sometimes result in greater effects than expected from either of the stress types alone. The aim of the present review is to provide a synthesis of existing knowledge on the interactions between effects of "natural" and chemical (anthropogenic) stressors. More than 150 studies were evaluated covering stressors including heat, cold, desiccation, oxygen depletion, pathogens and immunomodulatory factors combined with a variety of environmental pollutants. This evaluation revealed that synergistic interactions between the effects of various natural stressors and toxicants are not uncommon phenomena. Thus, synergistic interactions were reported in more than 50% of the available studies on these interactions. Antagonistic interactions were also detected, but in fewer cases. Interestingly, about 70% of the tested chemicals were found to compromise the immune system of humans as judged from studies on human cell lines. The challenge for future studies will therefore be to include aspects of combined stressors in effect and risk assessment of chemicals in the environment. Copyright 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Paul B. Tchounwou: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Int J Environ Res Public Health
                Journal ID (iso-abbrev): Int J Environ Res Public Health
                Journal ID (publisher-id): ijerph
                Title: International Journal of Environmental Research and Public Health
                Publisher: MDPI
                ISSN (Print): 1661-7827
                ISSN (Electronic): 1660-4601
                Publication date (Electronic): 07 April 2017
                Publication date (Print): April 2017
                Volume: 14
                Issue: 4
                Electronic Location Identifier: 389
                Affiliations
                [1 ]Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; mfox9@ 123456jhu.edu
                [2 ]Office of the Science Advisor, U.S. Environmental Protection Agency, Oak Ridge Institute for Science and Education (ORISE), Washington, DC 20004, USA; brewer.beth@ 123456epa.gov
                [3 ]Office of the Science Advisor, U.S. Environmental Protection Agency, Washington, DC 20004, USA
                Author notes
                [* ]Correspondence: martin.lawrence@ 123456epa.gov ; Tel.: +1-202-564-6497
                Article
                Publisher ID: ijerph-14-00389
                DOI: 10.3390/ijerph14040389
                PMC ID: 5409590
                PubMed ID: 28387705
                SO-VID: af2d850a-39bc-4925-8bbf-1493900385aa
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 05 December 2016
                Date accepted : 21 March 2017
                Categories
                Subject: Review

                ScienceOpen disciplines: Public health
                Keywords: cumulative risk assessment,nonchemical stressor,chemical mixture,vulnerable populations,community health,environmental justice,ecological health
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: cumulative risk assessment, nonchemical stressor, chemical mixture, vulnerable populations, community health, environmental justice, ecological health

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