设定制药行业中遗传毒性物质的职业接触限值。
Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry.
作者信息
Lovsin Barle Ester, Winkler Gian Christian, Glowienke Susanne, Elhajouji Azeddine, Nunic Jana, Martus Hans-Joerg
机构信息
*Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland
Novartis Pharma AG NIBR, Postfach, CH-4002 Basel, Switzerland; and.
出版信息
Toxicol Sci. 2016 May;151(1):2-9. doi: 10.1093/toxsci/kfw028.
In the pharmaceutical industry, genotoxic drug substances are developed for life-threatening indications such as cancer. Healthy employees handle these substances during research, development, and manufacturing; therefore, safe handling of genotoxic substances is essential. When an adequate preclinical dataset is available, a risk-based decision related to exposure controls for manufacturing is made following a determination of safe health-based limits, such as an occupational exposure limit (OEL). OELs are calculated for substances based on a threshold dose-response once a threshold is identified. In this review, we present examples of genotoxic mechanisms where thresholds can be demonstrated and OELs can be calculated, including a holistic toxicity assessment. We also propose a novel approach for inhalation Threshold of Toxicological Concern (TTC) limit for genotoxic substances in cases where the database is not adequate to determine a threshold.
在制药行业，具有基因毒性的原料药是针对癌症等危及生命的适应症而研发的。健康的员工在研究、开发和生产过程中会接触这些物质；因此，安全处理基因毒性物质至关重要。当有足够的临床前数据集时，在确定基于健康的安全限值（如职业接触限值（OEL））后，会做出与生产过程中的接触控制相关的基于风险的决策。一旦确定了阈值，就会根据阈值剂量反应为物质计算OEL。在本综述中，我们列举了一些基因毒性机制的例子，在这些例子中可以证明阈值并计算OEL，包括全面的毒性评估。我们还提出了一种新方法，用于在数据库不足以确定阈值的情况下，计算基因毒性物质的吸入毒理学关注阈值（TTC）限值。
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