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首页> 外文期刊>Alternatives to laboratory animals: ATLA >Biokinetic and toxicodynamic modelling and its role in toxicological research and risk assessment.
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Biokinetic and toxicodynamic modelling and its role in toxicological research and risk assessment.

机译：生物动力学和毒物动力学建模及其在毒理学研究和风险评估中的作用。

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摘要

Toxicological risk assessment for chemicals is still mainly based on highly standardised protocols for animal experimentation and exposure assessment. However, developments in our knowledge of general physiology, in chemicobiological interactions and in (computer-supported) modelling, have resulted in a tremendous change in our understanding of the molecular mechanisms underlying the toxicity of chemicals. This permits the development of biologically based models, in which the biokinetics as well as the toxicodynamics of compounds can be described. In this paper, the possibilities are discussed of developing systems in which the systemic (acute and chronic) toxicities of chemicals can be quantified without the heavy reliance on animal experiments. By integrating data derived from different sources, predictions of toxicity can be made. Key elements in this integrated approach are the evaluation of chemical functionalities representing structural alerts for toxic actions, the construction of biokinetic models on the basis of non-animal data (for example, tissue-blood partition coefficients, in vitro biotransformation parameters), tests or batteries of tests for determining basal cytotoxicity, and more-specific tests for evaluating tissue or organ toxicity. It is concluded that this approach is a useful tool for various steps in toxicological hazard and risk assessment, especially for those forms of toxicity for which validated in vitro and other non-animal tests have already been developed.
机译：化学品的毒理学风险评估仍主要基于高度标准化的动物实验和暴露评估协议。但是，我们在一般生理学，化学生物学相互作用和（计算机支持的）建模方面的知识的发展，导致我们对化学物质毒性的分子机制的理解发生了巨大变化。这允许开发基于生物学的模型，其中可以描述化合物的生物动力学和毒性动力学。在本文中，讨论了开发系统的可能性，在这些系统中，可以在不严重依赖动物实验的情况下对化学药品的系统（急性和慢性）毒性进行定量。通过整合来自不同来源的数据，可以做出毒性预测。这种综合方法的关键要素是评估代表毒性作用的结构警报的化学功能，基于非动物数据（例如组织-血液分配系数，体外生物转化参数）的生物动力学模型的构建，测试或用于确定基础细胞毒性的一系列测试，以及用于评估组织或器官毒性的更具体的测试。结论是，该方法是毒理学危害和风险评估中各个步骤的有用工具，尤其是对于已经开发了体外和其他非动物试验的毒性形式。

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