While regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests (which include mutagenicity assays). If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, but under most chemical regulations (except plant protection, biocides, pharmaceuticals), this is rare. The decision to conduct further testing based on genotoxicity test outcomes creates a regulatory gap for the identification of non-genotoxic carcinogens (NGTxC). With the objective of addressing this gap, in 2016, the Organization of Economic Cooperation and Development (OECD) established an expert group to develop an integrated approach to the testing and assessment (IATA) of NGTxC. Through that work, a definition of NGTxC in a regulatory context was agreed. Using the adverse outcome pathway (AOP) concept, various cancer models were developed, and overarching mechanisms and modes of action were identified. After further refining and structuring with respect to the common hallmarks of cancer and knowing that NGTxC act through a large variety of specific mechanisms, with cell proliferation commonly being a unifying element, it became evident that a panel of tests covering multiple biological traits will be needed to populate the IATA. Consequently, in addition to literature and database investigation, the OECD opened a call for relevant assays in 2018 to receive suggestions. Here, we report on the definition of NGTxC, on the development of the overarching NGTxC IATA, and on the development of ranking parameters to evaluate the assays. Ultimately the intent is to select the best scoring assays for integration in an NGTxC IATA to better identify carcinogens and reduce public health hazards.

虽然化学品致癌性测试的监管要求根据产品部门和监管管辖范围的不同而有所不同，但标准方法始于一系列基因毒性测试（包括致突变性测定）。如果任何体内基因毒性测试呈阳性，则可能需要进行终生啮齿动物癌症生物测定，但根据大多数化学法规（植物保护、生物杀灭剂、药品除外），这种情况很少见。根据基因毒性测试结果进行进一步测试的决定为非基因毒性致癌物 (NGTxC) 的鉴定造成了监管空白。为了弥补这一差距，经济合作与发展组织 (OECD) 于 2016 年成立了一个专家组，负责开发 NGTxC 测试和评估 (IATA) 的综合方法。通过这项工作，就监管背景下的 NGTxC 定义达成了一致。利用不良结果途径（AOP）概念，开发了各种癌症模型，并确定了总体机制和作用模式。在对癌症的共同特征进行进一步细化和构建后，并了解 NGTxC 通过多种特定机制发挥作用，而细胞增殖通常是一个统一因素，很明显，需要一组涵盖多种生物特征的测试填充 IATA。因此，除了文献和数据库调查之外，OECD 于 2018 年发起了相关分析的征集活动，以征求建议。在这里，我们报告了 NGTxC 的定义、总体 NGTxC IATA 的开发以及评估检测的排名参数的开发。最终目的是选择最佳的评分检测方法以集成到 NGTxC IATA 中，以更好地识别致癌物并减少公共健康危害。