Risk Sciences International, Ottawa, Canada.
Risk Sciences International, Ottawa, Canada; McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Canada.
Neurotoxicology. 2021 Mar;83:166-178. doi: 10.1016/j.neuro.2020.12.004. Epub 2020 Dec 5.
The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.
欧盟的 REACH 法规要求确定商业中化学物质的潜在健康和环境影响。本案例研究考察了 REACH 指南在三种高产量 (HPV) 铝 (Al) 物质的健康危害评估中的应用：金属铝、氧化铝和氢氧化铝。在铝暴露的潜在不良健康后果中，神经毒性是铝毒性最敏感的靶标之一，也是最关键的终点。本案例研究说明了将来自多条证据线的数据整合到 REACH 证据权重评估中的情况。本案例研究还解释了这些结果如何支持关于分类和标签的监管决策。在 REACH 对 Al 化合物的评估中面临的挑战包括形态、溶解度和生物利用度、评估因素的应用、外推原理以及与现有监管标准的差异。本案例研究中吸取的经验教训涉及到毒理学和流行病学数据的识别和评估；评估数据的相关性和可靠性；推导无效应水平 (DNEL) 的制定；解决数据空白和编写化学品安全报告。
