Center for Computational Toxicology and Exposure, United States Environmental Protection Agency, Research Triangle Park, NC, USA.
Centre for Safety of Substances and Products, National Institute for Public Health, And the Environment (RIVM), Bilthoven, the Netherlands.
Regul Toxicol Pharmacol. 2024 Jan;146:105525. doi: 10.1016/j.yrtph.2023.105525. Epub 2023 Nov 14.
In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.
2022 年 10 月,世界卫生组织(世卫组织)在葡萄牙里斯本召集了一个专家小组,重新评估了 2005 年世卫组织关于氯化二恶英类化合物的 TEFs。与之前采用专家判断和基于共识的 TEF 值分配的小组不同,目前的工作采用了 2006 年 REP 数据库的更新、基于共识的加权方案、贝叶斯剂量反应建模和荟萃分析,以得出“最佳估计”TEFs。更新后的数据库包含的数据集数量几乎是早期版本的两倍,并且包含了告知加权方案的元数据。对该数据集的贝叶斯分析导致了对同系物特异性效力的无偏定量评估,并带有不确定性估计。从该模型得出的“最佳估计”TEF 用于为几乎所有同系物分配 2022 年世卫组织-TEF,这些值没有像以前那样四舍五入到半对数。例外是单-邻位 PCB,由于这些化合物可用的数据有限且存在异质性,该小组同意保留其 2005 年世卫组织-TEF。将这些新的 TEFs 应用于在人乳和海鲜中测量的一组有限的二恶英类化学物质浓度表明,与使用 2005 年 TEFs 相比,总毒性当量往往会更低。