Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.
National Institute for Public Health and the Environment (RIVM), Utrecht, the Netherlands.
Environ Int. 2020 Sep;142:105828. doi: 10.1016/j.envint.2020.105828. Epub 2020 Jun 5.
A guidance document for the identification of endocrine disruptors (EDs) in the regulatory assessment of plant protection products (PPP) and biocidal products (BP) has been published by the European Chemical Agency (ECHA) and the European Food Safety Authority (EFSA). The ECHA/EFSA guidance, mainly addressing EATS (estrogen, androgen, thyroid, steroidogenesis) modalities, is intended to guide applicants and assessors of the competent regulatory authorities on the implementation of the scientific criteria for the determination of ED properties pursuant to the recently implemented PPP (EU 2018/605) and BP (EU 2017/2100) EU Regulations. In this study, a search filter for targeted literature search in context of assessing if a substance can be identified as an ED relevant for human health was developed and validated. Development of the search filter was based on the search strategy presented in the ECHA/EFSA guidance and using the estrogenic chemical Bisphenol AF (BPAF) as a model substance. Information specialists from two independent institutions developed refined search filters based on the suggested original search strategy published (ECHA/EFSA guidance - Appendix F). Articles identified by a systematic literature search for BPAF were screened for relevance with inclusion and exclusion criteria by two independent reviewers obtaining positive (relevant) and negative (irrelevant) controls. The developed search filter was quantitatively evaluated in terms of sensitivity, specificity and precision based on the positive and negative controls. The developed filter was then validated for T modality by its application to the known thyroid-disruptor perchlorate. The result is a sensitive search filter with sufficient specificity, which can be applied for all chemicals where a targeted literature search is needed to assess and identify ED properties of chemicals with relevance for humans. Future application of the filter to a broader range of chemicals may identify further points of improvement.
欧洲化学品管理局（ECHA）和欧洲食品安全局（EFSA）发布了一份关于在植物保护产品（PPP）和生物杀灭剂产品（BP）的监管评估中识别内分泌干扰物（ED）的指南文件。该 ECHA/EFSA 指南主要针对 EATS（雌激素、雄激素、甲状腺、类固醇生成）模式，旨在为 PPP（EU 2018/605）和 BP（EU 2017/2100）法规实施的、用于确定 ED 属性的科学标准，为有资质的主管当局的申请人和评估人员提供指导。在这项研究中，开发并验证了一种用于有针对性文献搜索的搜索筛选器，以评估一种物质是否可以被确定为与人类健康相关的 ED。搜索筛选器的开发是基于 ECHA/EFSA 指南中提出的搜索策略，并使用雌激素化学物质双酚 AF（BPAF）作为模型物质。来自两个独立机构的信息专家根据发布的建议原始搜索策略（ECHA/EFSA 指南-附录 F）开发了改进的搜索筛选器。通过两名独立评审员使用纳入和排除标准对系统文献搜索中确定的 BPAF 文章进行相关性筛选，获得阳性（相关）和阴性（不相关）对照。根据阳性和阴性对照，开发的搜索筛选器在灵敏度、特异性和精度方面进行了定量评估。然后，该筛选器通过应用于已知的甲状腺干扰物高氯酸盐，对 T 模式进行了验证。该结果是一种具有足够特异性的敏感搜索筛选器，可用于需要进行有针对性的文献搜索以评估和识别与人类相关的 ED 属性的所有化学品。未来将该筛选器应用于更广泛的化学品可能会发现进一步的改进点。
