人类对双A和六种数据较少的类似物体的内部暴露量,由基于生理学的动力学模型与多式参数化预测
Hélène Bigonne1, Amrei Rolof1, Inga Potapova1
1Department of Health Sciences and Technology, Institute of Food Nutrition and Health, ETH Zürich, CH-8092 Zürich, Switzerland.
新的模型预测双毒动力学,揭示了BPS和BPAF等BPA替代品的独特组织积累. 这有助于评估这些广泛使用的化学品对健康的风险.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
背景情况:
- 像BPAF,BPS和BPM这样的双 (BPs) 是常见的BPA替代品.
- 对它们的毒性动力学 (吸收,分布,新陈代谢,分泌) 的有限理解阻碍了对健康风险的评估.
- 人类广泛暴露需要更好的工具来评估潜在的不良影响.
研究的目的:
- 开发基于生理学的动力学 (PBK) 模型,用于预测内部双醇度.
- 在环境相关的暴露场景下比较各种双的毒动力学概况.
- 为了确定双积累的目标组织,并为风险评估提供信息.
主要方法:
- 开发了多个人类生理标准的PBK模型.
- 利用体外代谢数据,计算吸收预测,以及用于模型参数化的老鼠-人类推断.
- 根据BPA和BPS的现有人类毒动力学数据验证的模型.
主要成果:
- 在66%的病例中,模型准确地预测了关键的毒动力学参数 (Cmax,tmax,AUC) 在两倍差距内.
- 在不同双醇中观察到有毒动因特征的显著变化.
- 特定的双在某些组织中显示出优先积累:BPS (血液,丸),BPM (甲状腺),BPAF (乳房).
结论:
- 开发的PBK模型为评估双毒性动因学提供了一个强大的框架.
- 独特的组织分布模式突显了与BPA替代品相关的不同健康风险.
- 这些模型对于指导更安全地使用双醇和减轻潜在的健康影响至关重要.
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