Patlewicz G, Ball N, Boogaard P J, Becker R A, Hubesch B
DuPont Haskell Global Centers, 1090 Elkton Road, Newark, DE 19711, USA.
Toxicology & Environmental Research and Consulting (TERC), The Dow Chemical Company, Midland, MI 48674, USA.
Regul Toxicol Pharmacol. 2015 Jun;72(1):117-33. doi: 10.1016/j.yrtph.2015.03.015. Epub 2015 Apr 7.
Read-across is an alternative approach exploited to address information requirements for risk assessment and for regulatory programmes such as the European Union's REACH regulation. Whilst read-across approaches are accepted in principle, difficulties still remain in applying them consistently in practice. Recent work within Cefic LRI and ECETOC attempted to summarize the state-of-the-art and identify some of the barriers to broader acceptance of read-across approaches to overcome these. Acceptance is undoubtedly thwarted partly by the lack of a systematic framework to characterize the read-across justification and identify the uncertainties particularly for complex regulatory endpoints such as repeated-dose toxicity or prenatal developmental toxicity. Efforts are underway by the European Chemical's Agency (ECHA) to develop a Read-Across Assessment Framework (RAAF) and private sector experts have also considered the development of a similar framework. At the same time, mechanistic chemical categories are being proposed which are underpinned by Adverse Outcome Pathways (AOPs). Currently such frameworks are only focusing on discrete organic substances, though the AOP approach could conceivably be applied to evaluate more complex substances such as mixtures. Here we summarize the deliberations of the Cefic LRI read-across team in characterizing scientific confidence in the development and evaluation of read-across.
类推法是一种用于满足风险评估以及欧盟化学品注册、评估、授权和限制（REACH）法规等监管计划信息需求的替代方法。虽然类推法原则上已被接受，但在实际中始终如一地应用它们仍存在困难。欧洲化学工业理事会长期研究倡议（Cefic LRI）和欧洲毒理与化学毒物学中心（ECETOC）近期开展的工作试图总结当前的技术水平，并找出阻碍类推法更广泛接受的一些障碍，以便克服这些障碍。毫无疑问，缺乏一个系统框架来描述类推法的合理性并识别不确定性，尤其是对于重复剂量毒性或产前发育毒性等复杂监管终点而言，这在一定程度上阻碍了该方法的接受。欧洲化学品管理局（ECHA）正在努力制定一个类推评估框架（RAAF），私营部门的专家也考虑过制定类似框架。与此同时，正在提出基于不良结局途径（AOPs）的机制性化学类别。目前此类框架仅关注离散的有机物质，不过AOP方法可以想象地应用于评估更复杂的物质，如混合物。在此，我们总结了Cefic LRI类推法团队在描述类推法开发和评估中的科学可信度方面的审议情况。
