Uncertainty and confidence in applying mathematical models and in vitro data in toxicological safety assessments

近年来，人们面临着越来越大的压力，要求在产品风险评估中结束对动物实验的过度依赖，并在做出有关人类安全的决定时考虑来自非动物替代品的信息。与此同时，在开发基于计算机的人类生物学模拟器方面也进行了大量的研究工作。未来的风险评估应能够将先进的生物学模拟器与相关的非动物实验结合起来，以帮助风险评估人员在不使用动物的情况下预测不利的健康影响。目前，毒理学家对这些基于计算机的风险评估远没有对传统的基于动物的评估那么有信心。这部分是由于大多数使用计算机模型的调查只关注风险问题的一个小方面。我们认为完整的风险评估过程可以为人类安全评估提供更科学相关的信息。在我们的研究中，我们建立了一个连贯的框架，可以利用非动物实验和模拟器来开发新的安全评估方法。这些方法可以更好地预测对人类的潜在影响，减少可靠风险评估的时间和金钱成本，并减少对动物的依赖。

Over recent years, there has been increasing pressure to end the overreliance on animal experiments within product risk assessments and to consider the information from non-animal alternatives when making decisions about human safety. At the same time, there has been substantial research effort into the development of computer-based simulators of human biology. Future risk assessments should be able to combine advanced biology simulators with relevant non-animal experiments to help risk assessors make predictions about adverse health effects without the use of animals.Currently, toxicologists are far from having the same confidence in these computer-based risk assessments as they do in traditional animal-based assessments. This is partially due to most investigations of the use of the computer models focussing on just a small aspect of the risk problem. We consider the complete risk assessment process to provide more scientifically relevant information for human safety assessment. In our research, we build a coherent framework with which the non-animal experiments and simulators can be harnessed to develop new approaches for safety assessment. These approaches could give a better prediction of potential effects in humans, reduce the time and monetary costs of reliable risk assessment, and reduce the reliance on animals.