描述PFAS危害和风险:基于人群的体外心脏毒性评估策略
Lucie C Ford1, Hsing-Chieh Lin1, Yi-Hui Zhou2,3
1Department of Veterinary Physiology and Pharmacology, TAMU 4466, Texas A&M University, College Station, TX, 77843-4466, USA.
Human genomics
|September 1, 2024
概括
这项研究使用人类干细胞衍生的心脏细胞评估了56种per-和多基基物质 (PFAS) 的心脏毒性. 许多PFAS表现出影响,揭示了心脏毒性风险在人类中的显著变化.
科学领域:
- 环境毒理学环境毒理学
- 心血管毒理学心血管毒理学
- 干细胞生物学 干细胞生物学
背景情况:
- 和多醇基物质 (PFAS) 是广泛存在的环境污染物,毒理学数据有限.
- 心脏毒性是人类健康的一个重大问题,需要强大的查方法.
- 人类诱导多能干细胞 (iPSC) 衍生的心肌细胞为评估心脏毒性和个人间变异性提供了可行的模型.
研究的目的:
- 用人类iPSC衍生的心肌细胞来描述56个PFAS的心脏毒性危害,风险和个人间的变异性.
- 识别具有心脏毒性风险并表现出人类反应高变性的特定PFAS.
- 证明基于人群的体外方法对评估新出现的污染物的有用性.
主要方法:
- 通过度-反应测试,在不同的子类中测试了56个PFAS.
- 利用了来自16名健康捐赠者的人类iPSC衍生的心肌细胞.
- 采用动力流和高含量成像来评估像节拍频率,再极化和细胞毒性这样的表型.
主要成果:
- 在56种PFAS中,有46种在至少一个表型和供体中表现出度-反应效应.
- 在所有捐赠者中观察到对PFAS影响敏感性的显著个体间变异.
- 对20个PFAS进行了风险表征,其中大多数显示暴露幅度高于100.
结论:
- 这项研究确定了几种可能构成心脏毒性风险的PFAS,并表现出高度的个体间变异性.
- 人类iPSC衍生的心肌细胞对量化对PFAS反应的种群变化是有效的.
- 这些发现支持使用基于人体细胞的体外测试来优先考虑和评估新出现的污染物的风险.
相关概念视频
01:25Mutagenicity and Carcinogenicity
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
01:23Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...