Rorije Emiel, Aldenberg Tom, Buist Harrie, Kroese Dinant, Schüürmann Gerrit
National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands.
Regul Toxicol Pharmacol. 2013 Nov;67(2):146-56. doi: 10.1016/j.yrtph.2013.06.003. Epub 2013 Jun 19.
Within the EU FP6 project OSIRIS approaches to Integrated Testing Strategies (ITSs) were developed, with the aim to facilitate the use of non-test and non-animal testing information in regulatory risk assessment of chemicals. This paper describes an analytical Weight-of-Evidence (WoE) approach to an ITS for the endpoint of skin sensitisation. It specifically addresses the European chemicals legislation REACH, but the concept is readily applicable to ITS and WoE procedures in other regulatory frameworks, and for other toxicological endpoints. Bayesian statistics are applied to estimate the reliability of a conclusion on the sensitisation potential of a chemical, combining evidence from different information sources such as QSAR model predictions, in vitro and in vivo test results. The methodology allows for adaptation of the weight of individual information sources to account for the different levels of reliability of the individual ITS components. The calculated reliability of the WoE conclusion gives an objective, transparent and reproducible measure to decide if the information requirements for data evaluation are satisfied. Furthermore, in case the WoE is not sufficient, it gives the possibility to evaluate a priori if and how it will be possible to fulfil the information requirements with additional tests and/or model predictions.
在欧盟第六框架计划项目“奥西里斯”中，开发了综合测试策略（ITS）方法，旨在促进在化学品监管风险评估中使用非测试和非动物测试信息。本文描述了一种针对皮肤致敏终点的ITS的分析性证据权重（WoE）方法。它特别针对欧洲化学品法规《化学品注册、评估、授权和限制》（REACH），但该概念很容易应用于其他监管框架中的ITS和WoE程序，以及其他毒理学终点。应用贝叶斯统计来估计关于化学品致敏潜力结论的可靠性，结合来自不同信息源的证据，如定量构效关系（QSAR）模型预测、体外和体内测试结果。该方法允许调整各个信息源的权重，以考虑ITS各个组成部分的不同可靠性水平。计算得出的WoE结论的可靠性为判断数据评估的信息要求是否得到满足提供了一个客观、透明且可重复的衡量标准。此外，如果WoE不足，它还提供了一种可能性，即预先评估是否以及如何通过额外的测试和/或模型预测来满足信息要求。
