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传统和替代性毒性测试中的不良影响
Patience Browne1, Katie Paul Friedman2, Kim Boekelheide3
1Environment Health and Safety Division Environmental Directorate, Organisation for Economic and Cooperative Development (OECD), 2 rue André Pascal, Paris Cedex 16, 75775, France.
Regulatory toxicology and pharmacology : RTP
|February 3, 2024
概括
化学品安全评估通常使用动物研究的非特定终点来设定保护性人类暴露限值. 这种方法确保了广泛的安全性,即使不了解特定的毒理机制.
科学领域:
- 环境毒理学环境毒理学
- 风险评估 风险评估 风险评估
- 化学安全评估 化学安全评估
背景情况:
- 化学安全依赖于确定临界效应水平来设定人类暴露的限值.
- 当特定的机制未知时,经常使用非特定的终点 (例如,体重变化).
- 特定的尖端终点也被使用,但非特定的可以更敏感.
研究的目的:
- 鼓励重新评估如何在安全评估中解释有害化学物质的影响.
- 突出毒理学研究中非特异性终点的有用性.
- 促进对化学安全限值推导的更广泛理解.
主要方法:
- 对体内毒理学研究数据的分析.
- 使用非特定终点识别关键效应水平.
- 应用安全评估因素来推导暴露限值.
主要成果:
- 非特定的终点通常比特定的顶点终点更敏感.
- 动物数据被用来广泛确定保护性关键效应水平.
- 目前的方法推导出暴露水平,而不假定特定变化的直接人类相关性.
结论:
- 需要重新思考对有害化学物质影响的解释.
- 非特定的终点为导出保护性暴露水平提供了坚实的基础.
- 化学安全限制可以在没有精确的目标特定预测的情况下广泛保护.
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