دورية أكاديمية
أعرض في EDS

Systems Modeling of Developmental Vascular Toxicity.

التفاصيل البيبلوغرافية
العنوان: Systems Modeling of Developmental Vascular Toxicity.
المؤلفون: Saili KS; National Center for Computational Toxicology (NCCT), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA) Research Triangle Park NC 27711., Franzosa JA; National Center for Computational Toxicology (NCCT), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA) Research Triangle Park NC 27711., Baker NC; National Center for Computational Toxicology (NCCT), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA) Research Triangle Park NC 27711.; Leidos, Research Triangle Park NC 27711., Ellis-Hutchings RG; Toxicology and Environmental Research and Consulting The Dow Chemical Company, Midland, MI 48674., Settivari RS; Toxicology and Environmental Research and Consulting The Dow Chemical Company, Midland, MI 48674., Carney EW; Toxicology and Environmental Research and Consulting The Dow Chemical Company, Midland, MI 48674., Spencer R; ARA, Research Triangle Park NC 27711., Zurlinden TJ; National Center for Computational Toxicology (NCCT), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA) Research Triangle Park NC 27711., Kleinstreuer NC; National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS) Research Triangle Park, NC 27711., Li S; National Center for Advancing Translational Sciences (NCATS) National Institutes of Health, Bethesda, MD 20892., Xia M; National Center for Advancing Translational Sciences (NCATS) National Institutes of Health, Bethesda, MD 20892., Knudsen TB; National Center for Computational Toxicology (NCCT), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA) Research Triangle Park NC 27711.
المصدر: Current opinion in toxicology [Curr Opin Toxicol] 2019 Jun 01; Vol. 15 (1), pp. 55-63.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101697847 Publication Model: Print Cited Medium: Print ISSN: 2468-2934 (Print) Linking ISSN: 24682020 NLM ISO Abbreviation: Curr Opin Toxicol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : Elsevier B.V., [2016]-
مستخلص: The more than 80,000 chemicals in commerce present a challenge for hazard assessments that toxicity testing in the 21 st century strives to address through high-throughput screening (HTS) assays. Assessing chemical effects on human development adds an additional layer of complexity to the screening, with a need to capture complex and dynamic events essential for proper embryo-fetal development. HTS data from ToxCast/Tox21 informs systems toxicology models, which incorporate molecular targets and biological pathways into mechanistic models describing the effects of chemicals on human cells, 3D organotypic culture models, and small model organisms. Adverse Outcome Pathways (AOPs) provide a useful framework for integrating the evidence derived from these in silico and in vitro systems to inform chemical hazard characterization. To illustrate this formulation, we have built an AOP for developmental toxicity through a mode of action linked to embryonic vascular disruption (Aop43). Here, we review the model for quantitative prediction of developmental vascular toxicity from ToxCast HTS data and compare the HTS results to functional vascular development assays in complex cell systems, virtual tissues, and small model organisms. ToxCast HTS predictions from several published and unpublished assays covering different aspects of the angiogenic cycle were generated for a test set of 38 chemicals representing a range of putative vascular disrupting compounds (pVDCs). Results boost confidence in the capacity to predict adverse developmental outcomes from HTS in vitro data and model computational dynamics for in silico reconstruction of developmental systems biology. Finally, we demonstrate the integration of the AOP and developmental systems toxicology to investigate the unique modes of action of two angiogenesis inhibitors.
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معلومات مُعتمدة: EPA999999 United States ImEPA Intramural EPA
فهرسة مساهمة: Keywords: 5HPP-33; Adverse outcome pathway; TNP-470; Tox21; ToxCast; angiogenesis
تواريخ الأحداث: Date Created: 20200208 Latest Revision: 20210110
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7004230
DOI: 10.1016/j.cotox.2019.04.004
PMID: 32030360
قاعدة البيانات: MEDLINE
الوصف
تدمد:2468-2934
DOI:10.1016/j.cotox.2019.04.004