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首页> 外文期刊>Journal of applied toxicology >Integrated approach to testing and assessment for predicting rodent genotoxic carcinogenicity
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Integrated approach to testing and assessment for predicting rodent genotoxic carcinogenicity

机译：预测啮齿类动物遗传毒性致癌性的综合测试和评估方法

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We investigated the performance of an integrated approach to testing and assessment (IATA), designed to cover different genotoxic mechanisms causing cancer and to replicate measured carcinogenicity data included in a new consolidated database. Genotoxic carcinogenicity was predicted based on positive results from at least two genotoxicity tests: one in vitro and one in vivo (which were associated with mutagenicity categories according to the Globally Harmonized System classification). Substances belonging to double positives mutagenicity categories were assigned to be genotoxic carcinogens. In turn, substances that were positive only in a single mutagenicity test were assigned to be mutagens. Chemicals not classified by the selected genotoxicity endpoints were assigned to be negative genotoxic carcinogens and subsequently evaluated for their capability to elicit non-genotoxic carcinogenicity. However, non-genotoxic carcinogenicity mechanisms were not currently included in the developed IATA. The IATA is docked to the OECD Toolbox and uses measured data for different genotoxicity endpoints when available. Alternatively, the system automatically provides predictions by SAR genotoxicity models using the OASIS Tissue Metabolism Simulator platform. When the developed IATA was tested against the consolidated database, its performance was found to be high, with sensitivity of 74% and specificity of 83%, when measured carcinogenicity data were used along with predictions falling within the models' applicability domains. Performance of the IATA would be slightly changed to a sensitivity of 80% and specificity of 72% when the evaluation by non-genotoxic carcinogenicity mechanisms was taken into account. Copyright (c) 2016 John Wiley & Sons, Ltd.
机译：我们调查了综合测试和评估方法（IATA）的性能，该方法旨在涵盖导致癌症的不同遗传毒性机制，并复制新合并数据库中包含的测得致癌性数据。遗传毒性的致癌性是根据至少两项遗传毒性试验的阳性结果预测的：一项是体外试验，另一种是体内试验（根据全球协调制度分类，这与致突变性类别相关）。属于双阳性致突变性类别的物质被指定为遗传毒性致癌物。相应地，仅在单个诱变性测试中呈阳性的物质被指定为诱变剂。未按选定的遗传毒性终点分类的化学药品被定为阴性遗传毒性致癌物，随后对其引起非遗传毒性致癌性的能力进行了评估。但是，已开发的国际航空运输协会目前不包括非遗传毒性致癌机制。 IATA停靠在OECD工具箱中，并在可用时将测量数据用于不同的遗传毒性终点。或者，系统使用OASIS组织代谢模拟器平台通过SAR遗传毒性模型自动提供预测。当使用综合数据库对开发的IATA进行测试时，发现其性能很高，当使用测得的致癌性数据以及模型适用范围内的预测值时，灵敏度为74％，特异性为83％。当考虑到通过非遗传毒性致癌机制进行评估时，IATA的性能将略有变化，灵敏度为80％，特异性为72％。版权所有（c）2016 John Wiley＆Sons，Ltd.

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