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未来毒理学II:预测毒理学的体外数据和计算机模拟模型

FutureTox II: in vitro data and in silico models for predictive toxicology.

作者信息

Knudsen Thomas B, Keller Douglas A, Sander Miriam, Carney Edward W, Doerrer Nancy G, Eaton David L, Fitzpatrick Suzanne Compton, Hastings Kenneth L, Mendrick Donna L, Tice Raymond R, Watkins Paul B, Whelan Maurice

机构信息

United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, Sanofi, Bridgewater, New Jersey 08807, Page One Editorial Services, Boulder, Colorado 80304, Dow Chemical Company, Midland, Michigan 48674, Health and Environmental Sciences Institute, Washington, District of Columbia 20005, University of Washington, Seattle, Washington 98105, United States Food and Drug Administration, Silver Spring, Maryland 20993, Sanofi, Bethesda, Maryland 20814, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, University of North Carolina, Chapel Hill, North Carolina 27599, The Hamner Institutes, Research Triangle Park, North Carolina 27709, and European Commission Joint Research Centre, I-21027 Ispra, Italy.

United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, Sanofi, Bridgewater, New Jersey 08807, Page One Editorial Services, Boulder, Colorado 80304, Dow Chemical Company, Midland, Michigan 48674, Health and Environmental Sciences Institute, Washington, District of Columbia 20005, University of Washington, Seattle, Washington 98105, United States Food and Drug Administration, Silver Spring, Maryland 20993, Sanofi, Bethesda, Maryland 20814, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, University of North Carolina, Chapel Hill, North Carolina 27599, The Hamner Institutes, Research Triangle Park, North Carolina 27709, and European Commission Joint Research Centre, I-21027 Ispra, Italy

出版信息

Toxicol Sci. 2015 Feb;143(2):256-67. doi: 10.1093/toxsci/kfu234.

Abstract

FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology.

摘要

“未来毒理学II”是毒理学学会举办的一次毒理学当代概念研讨会,于2014年1月召开。会议目标是在落实美国国家研究委员会21世纪关于根据体外和计算机模拟数据预测体内反应愿景的背景下,回顾和讨论毒理学的科学现状,并确定未来目标。会上就代谢预测与建模、细胞生长与分化、对敏感亚群的影响以及将数据整合到风险评估中等优先关注问题进行了报告和讨论。还讨论了诸如干细胞衍生的人类细胞、3D器官型培养模型、细胞过程和形态发生的数学建模、不良结局途径开发以及体内系统的高内涵成像等技术的新趋势。尽管朝着基于体外/计算机模拟的风险评估范式取得进展是显而易见的,但也确定了这些领域的知识差距和技术局限性。针对肝毒性、癌症预测、发育毒性和监管毒理学等领域的未来方向和研究需求提出了具体建议。

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