一个 in vitro-in silico 工作流程,用于预测 PFAS 的干净
Hsing-Chieh Lin1, Courtney Sakolish1, Haley L Moyer1
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
这项研究开发了一种 in vitro-in silico 方法,用于预测人体脏清除每和多醇基物质 (PFAS). 该方法准确地估计了PFAS生物积累潜力,区分了缓慢和快速清除率.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 和多醇基物质 (PFAS) 具有可变的人类消除半衰期,受近管再吸收的影响.
- 准确预测多种PFAS的干净度 (CLrenal) 对人类健康风险评估至关重要.
- 需要采用体外模型和基于生理学的体外到体外抽取 (IVIVE) 来估计商业PFAS的CLrenal.
研究的目的:
- 用不同复杂度的体外模型比较PFAS的CLrenal预测.
- 为了评估结合 in vitro-in silico 工作流程的有效性,以估计人类的CLrenal.
- 评估工作流程根据清算率来区分PFAS的能力.
主要方法:
- 利用了人类近管上皮细胞 (RPTECs) 在96井板,静态24井Transwells和流体微生理系统中.
- 采用基于生理学的IVIVE和贝叶斯方法来分析PFAS度并估计体外透率.
- 测试了三个PFAS (PFOS,PFHxA,PFBS) 单独和混合物,使用in silico建模来预测体内.
主要成果:
- 人类CLrenal的In vitro-in silico工作流预测与现有的人体生物监测数据有很高的一致性.
- 缓慢清除和快速清除PFAS之间的相对CLrenal预测在2D培养和体内值之间高度一致.
- 更复杂的模型 (有或没有流量) 与绝对的CLrenal值有更大的一致性.
结论:
- 一个结合的 in vitro-in silico 工作流程有效地预测了 PFAS 的绝对 CLrenal.
- 这种方法可以准确地区分具有缓慢和快速清除率的PFAS.
- 工作流程有助于优先考虑在人类中具有更高生物积累潜力的PFAS.
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