在体外试验测试的截止值的统计推导
Christian T Willenbockel1, Mercedes Diez-Cocero1, Denise Bloch1
1Department of Pesticides Safety, German Federal Institute for Risk Assessment, Berlin, Germany.
ALTEX
|March 23, 2025
概括
现代统计方法提高了体外毒理危害分类的可靠性. 将不确定性量化和引导用于小数据集,可以改善眼睛刺激测试的切断值推导.
科学领域:
- 毒理学 毒理学 毒理学
- 监管科学 监管科学
- 统计建模 统计建模
背景情况:
- 越来越多地使用体外方法来对毒理危害进行分类.
- 监管验证将体外数据与体外数据进行比较,通常涉及数据转换.
- 当前的验证策略可能无法充分解决小数据集的局限性.
研究的目的:
- 应用先进的统计技术,如不确定性量化和引导,以改善体外方法验证.
- 通过使用现代统计方法,重新评估眼部刺激测试的现有切断值.
- 为了提高来自体外数据的危险分类的可靠性.
主要方法:
- 在现有的体外-体内生物数据集上利用了引导和不确定性量化 (Kaluzhny等人,2011年;Kolle等人,2015年).
- 将这些方法应用于OECD TG492 (体外) 和OECD TG 405 (体内) 的眼睛刺激数据.
- 建议的评估标准包括灵敏度,特异性和准确性与不确定性量化.
主要成果:
- 新得出的截止值为67%的平均组织活力,与经合组织的60%相比,提高了对植物保护产品 (PPP) 的敏感性.
- 对于液态单一物质,经合组织推的切断线得到确认.
- 现代统计方法证明了体外切线值的可靠性提高.
结论:
- 先进的统计方法对于在体外毒理学试验的可靠验证至关重要,特别是在小数据集的情况下.
- 使用这些技术修订和推导切断值可以提高危险分类的准确性.
- 这种方法为更强有力的监管接受体外方法提供了一条途径.
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