It is time to say goodbye to the standard two-year rodent bioassay. While a few, primarily genotoxic, compounds which are clearly associated with human cancer test positive in the bioassay, there is no science-based, sound foundation for presuming it provides either a valid broad (across different chemicals) capability for discerning potential human carcinogens or a valid starting point for making human risk assessment decisions. The two basic assumptions underlying the bioassay are: (1) rodent carcinogens are human carcinogens; and (2) results obtained at high doses are indicative of results that will occur at lower, environmentally relevant, doses. Both of these assumptions are not correct. Furthermore, a reevaluation of National Toxicology Program bioassay data has revealed that if the dose group size were increased from 50 to 200 rodents per group the number of bioassays deemed to be positive would increase from approximately 50% to very close to 100%. Thus, under the extreme conditions of the bioassay (e.g., high doses, lifetime exposure and, at times, a non-physiological route of administration) virtually all chemicals tested could be made into rodent carcinogens. In recent years there have been a number of proposals to move away from the standard bioassay. In particular, a recently formulated decision tree (Cohen, 2017), which places an emphasis on dose–response relationships and invites the use of MOA information, provides a sound basis for moving on from the bioassay and towards a rational approach to both identify chemicals which appear to have the potential to cause cancer in humans and take dose–response relationships into consideration in order to place the extent, if any, of the risk they might pose into proper perspective.

中文翻译：

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再见了生物测定法

现在该告别标准的两年啮齿动物生物测定法了。虽然少数几种与人类癌症有关的，主要是遗传毒性的化合物在生物测定法中呈阳性反应，但没有科学依据的可靠基础来推测它提供了有效的广泛（跨不同化学物质）能力来识别潜在的人类致癌物或制定人类风险评估决策的有效起点。生物测定法的两个基本假设是：（1）啮齿动物致癌物是人类致癌物；（2）以高剂量获得的结果表明将以较低的环境相关剂量发生的结果。这两个假设都不正确。此外，美国国家毒理学计划生物测定数据的重新评估显示，如果剂量组的大小从每组50只增加到200只啮齿动物，那么被认为是阳性的生物测定的数量将从大约50％增加到非常接近100％。因此，在生物测定的极端条件下（例如，高剂量，终生暴露以及有时采用非生理性给药途径）实际上所有被测试的化学物质都可以制成啮齿动物致癌物。近年来，已经有许多提议远离标准生物测定法。特别是，最近制定的决策树（Cohen，2017年）着重于剂量-反应关系并邀请使用MOA信息，这为从生物测定法转向采用合理方法识别化学物质提供了坚实的基础。它们似乎有可能在人类中引起癌症，并考虑到剂量-反应关系，以便适当地考虑他们可能构成的风险程度（如果有的话）。