Pípal Marek, Wiklund Linus, Caccia Sara, Beronius Anna
Institute of Environmental Medicine Karolinska Institutet Sweden.
EFSA J. 2022 May 25;20(Suppl 1):e200418. doi: 10.2903/j.efsa.2022.e200418. eCollection 2022 May.
Endocrine disruptors (EDs) are chemical substances that interfere with the endocrine system, adversely affecting human health and environment. Legislation with aim to eliminate and ban EDs have been introduced in EU, but the identification of EDs remains challenging and crucial step towards regulation and risk management. A guidance for ED assessment has been recently established for pesticides and biocides in the EU, which heavily relies on traditional toxicological testing . Most notably lacking mechanistic methods for some ED modalities and not covering many other modalities that might be affected by EDs. In this project, we focus on the ED assessment according to the valid legislation and explore the possibility to employ alternative methods to bolster the mechanistic understanding of the ED effects and eventually decrease the need for testing. We selected a well-studied industrial chemical perfluorooctanesulfonic acid (PFOS) to be a model compound in a case study for ED assessment where the EU criteria were applied in the frame of human health risk assessment with focus on thyroid disruption and developmental neurotoxicity. A systematic literature review has been conducted for these effects (Scopus, Pubmed, Embase), and relevant studies were selected by title/abstract screening (RAYYAN) and full-text examination. Selected studies were assessed for reliability (SciRAP), and all relevant data were extracted into a database and assessed by Weight of Evidence (WoE) approach. The initial analysis showed potential endocrine adverse effects and endocrine activity, meeting the ED criteria. The use of mechanistic and alternative methods enhanced the outcomes of WoE assessment. Also, the study provides a great hands-on experience with the most up-to-date development in the area of risk assessment and EDs.
内分泌干扰物（EDs）是干扰内分泌系统、对人类健康和环境产生不利影响的化学物质。欧盟已出台旨在消除和禁止内分泌干扰物的立法，但内分泌干扰物的识别仍然具有挑战性，是监管和风险管理的关键步骤。欧盟最近针对农药和生物杀灭剂制定了内分泌干扰物评估指南，该指南严重依赖传统毒理学测试。最明显的是，对于某些内分泌干扰物模式缺乏机制性方法，并且未涵盖可能受内分泌干扰物影响的许多其他模式。在本项目中，我们根据有效立法专注于内分泌干扰物评估，并探索采用替代方法来加强对内分泌干扰物效应的机制理解，最终减少测试需求的可能性。我们选择了一种经过充分研究的工业化学品全氟辛烷磺酸（PFOS）作为内分泌干扰物评估案例研究中的模型化合物，在人类健康风险评估框架内应用欧盟标准，重点关注甲状腺干扰和发育神经毒性。针对这些效应进行了系统的文献综述（Scopus、Pubmed、Embase），并通过标题/摘要筛选（RAYYAN）和全文审查选择了相关研究。对选定的研究进行可靠性评估（SciRAP），并将所有相关数据提取到数据库中，采用证据权重（WoE）方法进行评估。初步分析显示存在潜在的内分泌不良反应和内分泌活性，符合内分泌干扰物标准。机制性方法和替代方法的使用增强了证据权重评估的结果。此外，该研究还提供了在风险评估和内分泌干扰物领域最新发展方面的丰富实践经验。
