Integrated Laboratory Systems, Inc., P.O. Box 13501, Research Triangle Park, NC 27709, USA.
U.S. Environmental Protection Agency, 109 T.W. Alexander Dr., Research Triangle Park, NC 27709, USA.
Toxicol In Vitro. 2018 Mar;47:213-227. doi: 10.1016/j.tiv.2017.11.016. Epub 2017 Dec 5.
In vitro chemical safety testing methods offer the potential for efficient and economical tools to provide relevant assessments of human health risk. To realize this potential, methods are needed to relate in vitro effects to in vivo responses, i.e., in vitro to in vivo extrapolation (IVIVE). Currently available IVIVE approaches need to be refined before they can be utilized for regulatory decision-making. To explore the capabilities and limitations of IVIVE within this context, the U.S. Environmental Protection Agency Office of Research and Development and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods co-organized a workshop and webinar series. Here, we integrate content from the webinars and workshop to discuss activities and resources that would promote inclusion of IVIVE in regulatory decision-making. We discuss properties of models that successfully generate predictions of in vivo doses from effective in vitro concentration, including the experimental systems that provide input parameters for these models, areas of success, and areas for improvement to reduce model uncertainty. Finally, we provide case studies on the uses of IVIVE in safety assessments, which highlight the respective differences, information requirements, and outcomes across various approaches when applied for decision-making.
体外化学安全测试方法提供了高效、经济的工具，可用于对人类健康风险进行相关评估。为了实现这一潜力，需要将体外效应与体内反应联系起来，即体外到体内外推（IVIVE）。在可用于监管决策之前，目前可用的 IVIVE 方法需要进行改进。为了在这种情况下探索 IVIVE 的能力和局限性，美国环境保护署研究与发展办公室和国家毒理学计划机构间替代毒理学方法评估中心共同组织了一次研讨会和网络研讨会系列。在这里，我们整合了网络研讨会和研讨会的内容，讨论了促进 IVIVE 纳入监管决策的活动和资源。我们讨论了成功从有效体外浓度生成体内剂量预测的模型的特性，包括为这些模型提供输入参数的实验系统、成功领域以及改进以降低模型不确定性的领域。最后，我们提供了 IVIVE 在安全评估中的应用案例研究，这些案例研究突出了在应用于决策时，各种方法之间的差异、信息要求和结果。
