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通过整合基于PBTK建模的反向剂量计和体外生物测试来推导9,10-氨酸的基于健康的指导值

Da Zhang¹, Miaoying Shi², Junyu Ning¹

¹School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, 100013, China.

Environment international

|June 12, 2025

概括

新方法方法 (NAMs) 成功预测了9,10-氨酸 (9,10-AQ) 毒性,建立了与人类相关的基于健康的指导值 (HBGV). 这种经过验证的方法支持对9,10-AQ及其相关化合物的风险评估.

科学领域:

环境毒理学环境毒理学
计算毒理学计算毒理学
风险评估风险评估风险评估

背景情况:

antraquinones,包括9,10-anthraquinone (9,10-AQ),是环境污染物,具有潜在的慢性毒性.
有限的毒理学数据和资源密集的动物研究阻碍了对许多素的起点 (PoD) 和基于健康的指导值 (HB GV) 的推导.
需要有效和可靠的方法来评估 antraquinones 的健康风险.

研究的目的:

验证新方法方法 (NAMs) 以获得9.10-AQ的毒理指导值.
通过使用NAMs,为9,10-AQ建立与人类相关的基于健康的指导值 (HBGV).
为了证明NAMs在其他 antraquinones的风险评估中的潜力.

主要方法:

网络毒理学被用来通过脂质代谢来预测肝细胞缩.
肝G2细胞和高含量成像验证了9,10-AQ诱导的脂质积累.
针对老鼠和人类的生理学基础毒动力学 (PBTK) 模型被开发并用于反向剂量测量.

主要成果:

NAMs准确地预测了9,10-AQ诱导的肝脂代谢障碍.
对9,10-AQ.来说,人类相关的HBGV为0.0105 mg/kg的BW.
基于NAMs的HBGV与传统动物研究的值保持一致.

结论:

NAM提供了一种经过验证,高效和可靠的 in vitro-in silico 方法,用于预测化学毒性,并推导出与人类相关的指导值.
这种基于NAM的方法支持9,10-AQ和相关化合物的下一代风险评估 (NGRA).
该方法可以扩展到评估其他氨酸,提高风险评估能力.

关键词:

9,10-氨基 (9,10-AQ) 的使用基准剂量 (BMD) 是指基准剂量.基于健康的指导值 (HBGV)基于生理学的毒动力学 (PBTK) 模型.在体外到体外的定量抽取 (QIVIVE)

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