We recently published a next generation framework for assessing the risk of genomic damage via exposure to chemical substances. The framework entails a systematic approach with the aim to quantify risk levels for substances that induce genomic damage contributing to human adverse health outcomes. Here, we evaluated the utility of the framework for assessing the risk for industrial chemicals, using the case of benzene. Benzene is a well-studied substance that is generally considered a genotoxic carcinogen and is known to cause leukemia. The case study limits its focus on occupational and general population health as it relates to benzene exposure. Using the framework as guidance, available data on benzene considered relevant for assessment of genetic damage were collected. Based on these data, we were able to conduct quantitative analyses for relevant data sets to estimate acceptable exposure levels and to characterize the risk of genetic damage. Key observations include the need for robust exposure assessments, the importance of information on toxicokinetic properties, and the benefits of cheminformatics. The framework points to the need for further improvement on understanding of the mechanism(s) of action involved, which would also provide support for the use of targeted tests rather than a prescribed set of assays. Overall, this case study demonstrates the utility of the next generation framework to quantitatively model human risk on the basis of genetic damage, thereby enabling a new, innovative risk assessment concept. Environ. Mol. Mutagen. 61:94-113, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

中文翻译：

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下一代基因组损伤评估框架的实用性：使用工业化学品苯的案例研究。

我们最近发布了下一代框架，用于评估因接触化学物质而造成基因组损伤的风险。该框架需要采用系统方法，旨在量化导致基因组损伤、导致人类不良健康结果的物质的风险水平。在这里，我们以苯为例，评估了工业化学品风险评估框架的实用性。苯是一种经过充分研究的物质，通常被认为是一种遗传毒性致癌物，并已知会导致白血病。该案例研究限制了对职业和一般人群健康的关注，因为它与苯暴露有关。以该框架为指导，收集了与遗传损害评估相关的苯的可用数据。基于这些数据，我们能够对相关数据集进行定量分析，以估计可接受的暴露水平并表征遗传损伤的风险。主要观察结果包括需要进行稳健的暴露评估、毒代动力学特性信息的重要性以及化学信息学的好处。该框架指出需要进一步提高对所涉及作用机制的理解，这也将为使用有针对性的测试而不是一组规定的检测提供支持。总体而言，本案例研究展示了下一代框架在基于遗传损伤的基础上对人类风险进行定量建模的实用性，从而实现了新的、创新的风险评估概念。环境。摩尔。诱变剂。61:94-113, 2020。© 2019 作者。环境和分子诱变由 Wiley periodicals, Inc. 代表环境诱变协会出版。