Schrenk Dieter
Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schroedinger-Strasse 52, D-67663 Kaiserslautern, Germany.
Toxicol Rep. 2018 Apr 7;5:504-511. doi: 10.1016/j.toxrep.2018.04.002. eCollection 2018.
Chemical Carcinogens are compounds which can cause cancer in humans and experimental animals. This property is attributed to many chemicals in the public discussion, resulting in a widespread perception of danger and threat. In contrast, a scientific analysis of the wide and non-critical use of the term 'carcinogenic' is warranted. First, it has to be clarified if the compound acts in a genotoxic or non-genotoxic manner. In the latter case, an ineffective (safe) threshold dose without cancer risk can be assumed. In addition, it needs to be investigated if the mode-of-action causing tumors in laboratory animals is relevant at all for humans. In case the compound is clearly directly genotoxic, an ineffective threshold dose cannot be assumed. However, also in this case it is evident that high doses of the compound are generally associated with a high cancer risk, low doses with a lower one. Based on dose-response data from animal experiments, quantification of the cancer risk is carried out by mathematical modeling. If the safety margin between the lowest carcinogenic dose in animals and the relevant level of exposure in humans exceeds 10,000, the degree of concern is classified as low. Cases, where the compound turns out to be genotoxic in one study or one test only but not in others or only but not , are particularly difficult to explain and cause controversial discussions. Also for indirectly genotoxic agents, an ineffective (threshold) dose must be assumed. The situation is aggravated by the use of doubtful epidemiological studies in humans such as in the case of glyphosate, where data from mixed exposure to various chemicals were used. If such considerations are mixed with pure hazard classifications such as 'probably carcinogenic in humans' ignoring dose-response behavior and mode-of-action, the misinformation and public confusion are complete. It appears more urgent but also more difficult than ever to return to a scientifically based perception of these issues.
化学致癌物是能够在人类和实验动物中引发癌症的化合物。在公众讨论中，许多化学物质都被认为具有这种特性，这导致了人们对危险和威胁的普遍认知。相比之下，有必要对“致癌”这一术语的广泛且不严谨的使用进行科学分析。首先，必须明确该化合物是以基因毒性方式还是非基因毒性方式起作用。在后一种情况下，可以假定存在一个无癌症风险的无效（安全）阈值剂量。此外，还需要研究在实验动物中导致肿瘤的作用方式是否与人类完全相关。如果该化合物明显具有直接基因毒性，则不能假定存在无效阈值剂量。然而，即便如此，显然高剂量的该化合物通常与高癌症风险相关，低剂量则与较低风险相关。基于动物实验的剂量反应数据，通过数学建模对癌症风险进行量化。如果动物中最低致癌剂量与人类相关暴露水平之间的安全系数超过10000，则关注程度被归类为低。仅在一项研究或一项测试中显示该化合物具有基因毒性而在其他研究或测试中未显示，或者仅在某些条件下显示而在其他条件下未显示的情况，特别难以解释，并会引发有争议的讨论。对于间接基因毒性剂，也必须假定存在一个无效（阈值）剂量。在人类中使用可疑的流行病学研究（如草甘膦的情况，其中使用了多种化学物质混合暴露的数据）会使情况更加复杂。如果将这些考虑因素与诸如“可能对人类致癌”等纯粹的危害分类混为一谈，而忽略剂量反应行为和作用方式，那么错误信息和公众困惑就会达到极致。回归到基于科学的对这些问题的认知，似乎比以往任何时候都更加紧迫但也更加困难。
