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Advancing the adverse outcome pathway framework-An international horizon scanning approach.

ABSTRACT: Our ability to conduct whole-organism toxicity tests to understand chemical safety has been outpaced by the synthesis of new chemicals for a wide variety of commercial applications. As a result, scientists and risk assessors are turning to mechanistically based studies to increase efficiencies in chemical risk assessment and making greater use of in vitro and in silico methods to evaluate potential environmental and human health hazards. In this context, the adverse outcome pathway (AOP) framework has gained traction in regulatory science because it offers an efficient and effective means for capturing available knowledge describing the linkage between mechanistic data and the apical toxicity end points required for regulatory assessments. A number of international activities have focused on AOP development and various applications to regulatory decision-making. These initiatives have prompted dialogue between research scientists and regulatory communities to consider how best to use the AOP framework. Although expert-facilitated discussions and AOP development have been critical in moving the science of AOPs forward, it was recognized that a survey of the broader scientific and regulatory communities would aid in identifying current limitations while guiding future initiatives for the AOP framework. To that end, a global horizon scanning exercise was conducted to solicit questions concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision-making. The questions received fell into several broad topical areas: AOP networks, quantitative AOPs, collaboration on and communication of AOP knowledge, AOP discovery and development, chemical and cross-species extrapolation, exposure/toxicokinetics considerations, and AOP applications. Expert ranking was then used to prioritize questions for each category, where 4 broad themes emerged that could help inform and guide future AOP research and regulatory initiatives. In addition, frequently asked questions were identified and addressed by experts in the field. Answers to frequently asked questions will aid in addressing common misperceptions and will allow for clarification of AOP topics. The need for this type of clarification was highlighted with surprising frequency by our question submitters, indicating that improvements are needed in communicating the AOP framework among the scientific and regulatory communities. Overall, horizon scanning engaged the global scientific community to help identify key questions surrounding the AOP framework and guide the direction of future initiatives. Environ Toxicol Chem 2017;36:1411-1421. © 2017 SETAC.

SUBMITTER: LaLone CA

PROVIDER: S-EPMC6156781 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Advancing the adverse outcome pathway framework-An international horizon scanning approach.

LaLone Carlie A CA Ankley Gerald T GT Belanger Scott E SE Embry Michelle R MR Hodges Geoff G Knapen Dries D Munn Sharon S Perkins Edward J EJ Rudd Murray A MA Villeneuve Daniel L DL Whelan Maurice M Willett Catherine C Zhang Xiaowei X Hecker Markus M

Environmental toxicology and chemistry 20170601 6

Our ability to conduct whole-organism toxicity tests to understand chemical safety has been outpaced by the synthesis of new chemicals for a wide variety of commercial applications. As a result, scientists and risk assessors are turning to mechanistically based studies to increase efficiencies in chemical risk assessment and making greater use of in vitro and in silico methods to evaluate potential environmental and human health hazards. In this context, the adverse outcome pathway (AOP) framewo ...[more]

PMID: 28543973

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Project description:BackgroundDecades of research to understand the impacts of various types of environmental occupational and medical stressors on human health have produced a vast amount of data across many scientific disciplines. Organizing these data in a meaningful way to support risk assessment has been a significant challenge. To address this and other challenges in modernizing chemical health risk assessment, the Organisation for Economic Cooperation and Development (OECD) formalized the adverse outcome pathway (AOP) framework, an approach to consolidate knowledge into measurable key events (KEs) at various levels of biological organisation causally linked to disease based on the weight of scientific evidence (http://oe.cd/aops). Currently, AOPs have been considered predominantly in chemical safety but are relevant to radiation. In this context, the Nuclear Energy Agency's (NEA's) High-Level Group on Low Dose Research (HLG-LDR) is working to improve research co-ordination, including radiological research with chemical research, identify synergies between the fields and to avoid duplication of efforts and resource investments. To this end, a virtual workshop was held on 7 and 8 October 2020 with experts from the OECD AOP Programme together with the radiation and chemical research/regulation communities. The workshop was a coordinated effort of Health Canada, the Electric Power Research Institute (EPRI), and the Nuclear Energy Agency (NEA). The AOP approach was discussed including key issues to fully embrace its value and catalyze implementation in areas of radiation risk assessment.ConclusionsA joint chemical and radiological expert group was proposed as a means to encourage cooperation between risk assessors and an initial vision was discussed on a path forward. A global survey was suggested as a way to identify priority health outcomes of regulatory interest for AOP development. Multidisciplinary teams are needed to address the challenge of producing the appropriate data for risk assessments. Data management and machine learning tools were highlighted as a way to progress from weight of evidence to computational causal inference.

Project description:IntroductionThe CIAO project was launched in Spring 2020 to address the need to make sense of the numerous and disparate data available on COVID-19 pathogenesis. Based on a crowdsourcing model of large-scale collaboration, the project has exploited the Adverse Outcome Pathway (AOP) knowledge management framework built to support chemical risk assessment driven by mechanistic understanding of the biological perturbations at the different organizational levels. Hence the AOPs might have real potential to integrate data produced through different approaches and from different disciplines as experienced in the context of COVID-19. In this study, we aim to address the effectiveness of the AOP framework (i) in supporting an interdisciplinary collaboration for a viral disease and (ii) in working as the conceptual mediator of a crowdsourcing model of collaboration.MethodsWe used a survey disseminated among the CIAO participants, a workshop open to all interested CIAO contributors, a series of interviews with some participants and a self-reflection on the processes.ResultsThe project has supported genuine interdisciplinarity with exchange of knowledge. The framework provided a common reference point for discussion and collaboration. The diagram used in the AOPs assisted with making explicit what are the different perspectives brought to the knowledge about the pathways. The AOP-Wiki showed up many aspects about its usability for those not already in the world of AOPs. Meanwhile their use in CIAO highlighted needed adaptations. Introduction of new Wiki elements for modulating factors was potentially the most disruptive one. Regarding how well AOPs support a crowdsourcing model of large-scale collaboration, the CIAO project showed that this is successful when there is a strong central organizational impetus and when clarity about the terms of the collaboration is brought as early as possible.DiscussionExtrapolate the successful CIAO approach and related processes to other areas of science where the AOP could foster interdisciplinary and systematic organization of the knowledge is an exciting perspective.

Project description:BackgroundTo solve current issues using big data, solve current issues related to the semiconductor and electronics industry, I tried to establish the data for each toxicity mechanism for adverse outcome pathway (AOP) for the exposure.ObjectiveI planned to increase the efficiency of human hazard assessment by searching, analyzing, and linking test data on the relationship between key events occurred at each level, which are the biological targets of chemicals in semiconductor manufacturing.ResultsIt was found that 48 kinds of chemicals had 11 AOPs, while 103 chemicals had multiple AOPs, and 26 had case evidence. As a result of AOP analysis, it was found that a total of 320 chemicals had 42 AOPs, and 190 major chemicals corresponded to 11 AOPs. It was found necessary to develop a complex AOP and secure an (inhalation or dermal) exposure scenario for combined exposure at work. As a comparative search (41 out of 190 chemicals) of biomarkers specific to occupational diseases, 12 biomarkers were found to be related to breast cancer. The AOPs for 50 specific chemicals were presented, together with occupational disease-specific AOPs and key events relationship from 50 chemicals, and taxonomic classification for each AOP analysis could be found. With a comparative search, 41 out of 190 chemicals were associated with specific biomarkers for occupational diseases, and 12 mRNA or protein biomarkers were found to be related to breast cancer by cross-validation with the attached Table 24 of the Enforcement Regulations of the OSHAct and the CTD.ConclusionThe mechanism of occupational diseases caused by chemicals was presented, together with pathological preventions. I believe that a strategy is needed to expand the target organization for each chemical by linking with activities, such as work environment measurement, and cooperating with screening items and methods suitable for toxic chemicals, like AOP tools.Supplementary informationThe online version contains supplementary material available at 10.1007/s13273-021-00139-4.

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Advancing the adverse outcome pathway framework-An international horizon scanning approach.

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Advancing the adverse outcome pathway framework-An international horizon scanning approach.

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