推进使用新的方法方法来评估致性:建立一个分层的方法
Reproductive toxicology (Elmsford, N.Y.)
|August 5, 2023
概括
新方法方法 (NAMs) 有效地评估化学物质的致性. 结合了三种方法 - - 晶体DART,devTox和斑马鱼胚胎毒性测试 - - 显著提高了发育毒性评估的预测准确性.
科学领域:
- 毒理学 毒理学 毒理学
- 发展生物学 发展生物学
- 计算化学计算化学
背景情况:
- 新方法方法 (NAM) 对于评估新成分的安全性至关重要.
- 鉴于机械复杂性,评估生殖毒性和产性是高度优先考虑的.
研究的目的:
- 用多种in silico和in vitro模型选化学物质以检测它们的致性潜力.
- 评估单个和组合NAM的灵敏度和特异性,以预测产性.
主要方法:
- 对46种非致病性化学物质和39种致病性化学物质进行选.
- 使用了经合组织QSAR工具箱的DART模型,devTox quickPredictTM测试和斑马鱼胚胎毒性测试 (ZET).
- 应用了"二分之三规则"和决策树方法进行组合分析.
主要成果:
- 个别测试显示了不同的灵敏度和特异性 (DART: 94.7%/84.1%, devTox: 86.1%/35.6%, ZET: 77.8%/76.7%).
- 结合"三分之二规则",提高了96.0%的灵敏度和71.4%的特异性.
- 对85种化学品的决策树方法显示了90%的可预测性和稳定性.
结论:
- 这三个NAM都表现出良好的灵敏度和特异性.
- 结合检测结果,特别是通过"三分之二规则"或决策树,可以提高对原性潜力的预测准确度.
- 一个分层决策树的方法提供了一个强大的策略来评估化学产性.
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