口服重复剂量毒性测试结果的不确定性:对监管分类的影响
Atanas Chapkanov1, Terry W Schultz2, Ovanes G Mekenyan1
1Laboratory of Mathematical Chemistry, Prof. As. Zlatarov University, Bourgas, Bulgaria.
Regulatory toxicology and pharmacology : RTP
|December 9, 2023
概括
毒性数据的监管分类是不确定的. 超过40%的化学品显示使用最低观察到 (不良) 影响水平 (LO(A) EL) 值的模糊分类,有可能在全球协调系统 (GHS) 中错误分类.
科学领域:
- 毒理学 毒理学 毒理学
- 风险评估 风险评估
- 化学品法规 化学品法规
背景情况:
- 最低观察 (不良) 效应水平 (LOA) 值是量化重复剂量毒性 (RDT) 的关键出发点 (PoD) 值.
- 监管分类严重依赖于这些PoD值,但它们固有的不确定性可能会影响决策.
研究的目的:
- 调查源自LO(A) EL值的监管分类中的不确定性.
- 量化这种不确定性对全球协调体系 (GHS) 中化学品分类的影响.
主要方法:
- 对大数据集进行了剂量-反应近似值,包括潜在的霍尔梅西斯区域.
- 计算了最小效应剂量 (MED),并使用MED/LO(A) EL比率来评估跨性别和检查项目的实验不确定性.
- 分析了不确定性对GHS分类的影响,确定了含糊地分类化学品的百分比.
主要成果:
- 超过40%的研究化学品在GHS体系下表现出模两可的分类.
- 当监管决策仅依赖于单个LO (A) EL值时,发现了错误分类的重大潜力.
- 详细介绍灰色区域和GHS分类分布的表格已生成,以帮助实际应用.
结论:
- 与LO (A) EL值相关的不确定性对明确的化学分类构成重大挑战.
- 目前依赖单一的LO (A) EL值可能导致错误分类,需要在风险评估中采取更细致的方法.
- 开发的表格提供了工具,以更好地将研发与开发技术的不确定性纳入监管实践和风险管理.
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