Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory, and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, USA.
Bioinformatics Research Center, Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
J Hazard Mater. 2022 Jun 5;431:128615. doi: 10.1016/j.jhazmat.2022.128615. Epub 2022 Mar 2.
Per- and polyfluoroalkyl substances (PFAS) are a class of widely used chemicals with limited human health effects data relative to the diversity of structures manufactured. To help fill this data gap, an extensive in vivo developmental toxicity screen was performed on 139 PFAS provided by the US EPA. Dechorionated embryonic zebrafish were exposed to 10 nominal water concentrations of PFAS (0.015-100 µM) from 6 to 120 h post-fertilization (hpf). The embryos were assayed for embryonic photomotor response (EPR), larval photomotor response (LPR), and 13 morphological endpoints. A total of 49 PFAS (35%) were bioactive in one or more assays (11 altered EPR, 25 altered LPR, and 31 altered morphology). Perfluorooctanesulfonamide (FOSA) was the only structure that was bioactive in all 3 assays, while Perfluorodecanoic acid (PFDA) was the most potent teratogen. Low PFAS volatility was associated with developmental toxicity (p < 0.01), but no association was detected between bioactivity and five other physicochemical parameters. The bioactive PFAS were enriched for 6 supergroup chemotypes. The results illustrate the power of a multi-dimensional in vivo platform to assess the developmental (neuro)toxicity of diverse PFAS and in the acceleration of PFAS safety research.
全氟和多氟烷基物质（PFAS）是一类广泛使用的化学品，相对于制造的结构多样性而言，其对人类健康的影响数据有限。为了帮助填补这一数据空白，美国环保署提供了 139 种 PFAS，对其进行了广泛的体内发育毒性筛选。去壳斑马鱼胚胎在受精后 6 至 120 小时（hpf），暴露于 10 种名义水浓度（0.015-100 µM）的 PFAS 中。对胚胎进行胚胎光运动反应（EPR）、幼鱼光运动反应（LPR）和 13 种形态学终点检测。共有 49 种 PFAS（35%）在一种或多种检测中具有生物活性（11 种改变 EPR，25 种改变 LPR，31 种改变形态）。全氟辛烷磺酰胺（FOSA）是唯一在所有 3 种检测中均具有生物活性的结构，而全氟癸酸（PFDA）是最有效的致畸物。低 PFAS 挥发性与发育毒性相关（p<0.01），但在生物活性与其他五个物理化学参数之间未检测到相关性。生物活性 PFAS 富集了 6 个超级组化学型。结果表明，多维体内平台在评估不同 PFAS 的发育（神经）毒性方面具有强大作用，并加速了 PFAS 安全性研究。
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