Hazard identification, classification, and risk assessment of carcinogens: too much or too little? – Report of an ECETOC workshop
Hazard identification, classification, and risk assessment of carcinogens: too much or too little? – Report of an ECETOC workshop
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致癌物的危害识别、分类和风险评估：太多还是太少？ECETOC 研讨会报告
DOI：
10.1080/10408444.2020.1727843
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发表时间：
2020
影响因子：
5.9
通讯作者：
U. Sauer
中科院分区：
文献类型：
--
作者：
S. Felter;A. Boobis;P. Botham;Alice Brousse;H. Greim;H. Hollnagel;U. Sauer
摘要欧洲化学品生态毒理学和毒理学中心（ECETOC）组织了一次题为“致癌物的危害识别、分类和风险评估：太多还是太少？”的研讨会。探讨目前将物质分为致癌或非致癌的二元致癌性分类方案的科学局限性。分类通常基于啮齿动物2年生物测定法，该方法具有科学局限性，不需要预测物质是否可能是人类致癌物。相比之下，建立在新方法学（NAM）基础上的分层测试策略，随后进行亚慢性毒性测试（如有必要），可用于确定物质是否可能致癌，会发生何种作用模式效应，以及对于非遗传毒性致癌物，低于导致致癌性的关键事件不受影响的剂量水平。重要的是，目的不是让NAM模拟体内记录的高剂量效应，因为这些效应与人体风险评估无关。在“最大耐受剂量”下进行的致癌性试验不能反映人体接触条件，但会导致体内平衡的严重紊乱，而在相关的人体接触水平下不太可能发生这种情况。对结果的评价应考虑生物学相关性，而不仅仅是统计学意义。使用这种方法，可以确定非遗传毒性物质的安全暴露。
Abstract The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) organized a workshop “Hazard Identification, Classification and Risk Assessment of Carcinogens: Too Much or Too Little?” to explore the scientific limitations of the current binary carcinogenicity classification scheme that classifies substances as either carcinogenic or not. Classification is often based upon the rodent 2-year bioassay, which has scientific limitations and is not necessary to predict whether substances are likely human carcinogens. By contrast, tiered testing strategies founded on new approach methodologies (NAMs) followed by subchronic toxicity testing, as necessary, are useful to determine if a substance is likely carcinogenic, by which mode-of-action effects would occur and, for non-genotoxic carcinogens, the dose levels below which the key events leading to carcinogenicity are not affected. Importantly, the objective is not for NAMs to mimic high-dose effects recorded in vivo, as these are not relevant to human risk assessment. Carcinogenicity testing at the “maximum tolerated dose” does not reflect human exposure conditions, but causes major disturbances of homeostasis, which are very unlikely to occur at relevant human exposure levels. The evaluation of findings should consider biological relevance and not just statistical significance. Using this approach, safe exposures to non-genotoxic substances can be established.
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影响因子：
11.2
作者：
S. Cohen;L. Ellwein
通讯作者：
S. Cohen;L. Ellwein
DOI：
10.1007/978-3-319-66084-4
发表时间：
2018-02
期刊：
Computer Engineering
影响因子：
--
作者：
N. Garcia-Reyero;Cheryl A. Murphy
通讯作者：
N. Garcia-Reyero;Cheryl A. Murphy
传统的毒理学范式是正确的：剂量影响机制。
影响因子：
10.4
作者：
Goodman,JI
通讯作者：
Goodman,JI
影响因子：
13.5
作者：
Morgan MM;Johnson BP;Livingston MK;Schuler LA;Alarid ET;Sung KE;Beebe DJ
通讯作者：
Beebe DJ