Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry

被引：9
|
作者：
Barle, Ester Lovsin [1 ]
Winkler, Gian Christian [2 ]
Glowienke, Susanne [2 ]
Elhajouji, Azeddine [2 ]
Nunic, Jana [3 ]
Martus, Hans-Joerg [2 ]
机构：
[1] Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland
[2] Novartis Pharma AG NIBR, Postfach, CH-4002 Basel, Switzerland
[3] Lek Pharmaceut DD, Verovskova 57, Ljubljana 1526, Slovenia
来源：
TOXICOLOGICAL SCIENCES | 2016年 / 151卷 / 01期
关键词：
occupational exposure limit; genotoxicity; threshold; acceptable risk; TTC; DOSE-RESPONSE RELATIONSHIPS; IN-VITRO; POTENTIAL THRESHOLDS; IWGT REPORT; MUTAGENESIS; MECHANISMS; METRICS; ASSAY;
D O I：
10.1093/toxsci/kfw028
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
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.
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收藏
页码：2 / 9
页数：8
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