The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B₁, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs.

化学致癌物的风险评估是毒理学的一项主要任务。尽管在过去几十年中暴露已得到有效缓解，但食品和工作场所中的低水平致癌物质仍然存在，而且往往无法完全避免。传统上，遗传毒性和非遗传毒性致癌物之间的区别被认为与风险评估特别相关，假设后者存在无效应浓度（阈值水平）。相比之下，基因毒性致癌物、其代谢前体和 DNA 反应性代谢物被认为是所有浓度下的危险因素，因为即使是一种或几种 DNA 损伤原则上也可能导致突变，从而增加肿瘤风险。在当前文件中，基于有关所研究物质（组）的机械知识，并考虑到用于量化 DNA 损伤和突变以及“组学”的分析技术的最新改进，提出了对基因毒性致癌物的更新风险评估接近。此外，只要有可能和适当，就会特别注意相同或可比较 DNA 损伤的背景水平的整合。在 A 部分中，基本考虑因素强调了与非基因毒性物质相比，基因毒性物质的 DNA 反应性方面的危害和风险。此外，还描述了遗传毒理学以及暴露剂量测定中当前使用的方法。特别关注作用模式 (MOA) 的阐明以及 DNA 损伤与癌症风险之间的关系。B 部分阐述了遗传毒性致癌物的具体例子，包括人类接触的外源性和内源性致癌物，例如甲醛、乙醛和相应的醇以及一些烷化剂、环氧乙烷和丙烯酰胺，还包括黄曲霉毒素等外源性致癌物的例子B ₁、烯丙基烷氧基苯、2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉(MeIQx)、苯并[ a ]芘和吡咯里西啶生物碱。此外，还特别关注一些致癌金属化合物，这些化合物被认为是间接基因毒素，即使在低暴露条件下，也会通过与细胞对 DNA 损伤的反应相互作用来加速致突变性。C 部分最后包含结论和观点，提出了评估与接触基因毒性化合物相关的致癌风险的完善策略并满足研究需求。