Assessment of unique behavioral, morphological, and molecular alterations in the comparative developmental toxicity profiles of PFOA, PFHxA, and PFBA using the zebrafish model system.
Assessment of unique behavioral, morphological, and molecular alterations in the comparative developmental toxicity profiles of PFOA, PFHxA, and PFBA using the zebrafish model system.
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DOI：
10.1016/j.envint.2022.107642
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发表时间：
2022-12
影响因子：
11.8
通讯作者：
Freeman, Jennifer L.
中科院分区：
文献类型：
--
作者：
Wasel, Ola;Thompson, Kathryn M.;Freeman, Jennifer L.
全氟烷基物质（PFAS）是一类在环境中持续存在的合成化学品。由于与长链PFAS相关的不良健康后果，使用了短链化学品作为替代品，但短链化学品的发育毒性评估有限。比较了三种全氟烷基酸（PFAAs）[由8碳（C8）、全氟己酸（PFHxA, C6）和全氟丁酸（PFBA, C4）组成的全氟辛酸（PFOA）]对发育中的斑马鱼（Danio rerio）的毒性。lc50在受精后120 h （hpf）通过将发育中的斑马鱼（1-120 hpf）暴露在浓度范围内来评估每种PFAA的效力。然后在整个胚胎发生过程中（1-72 hpf）暴露于亚致死浓度（0.4-4000 ppb, μg/L）。胚胎暴露对运动活动的影响通过120 hpf的视觉运动反应测试来完成。在72 hpf时，测定形态学变化（总体长、头长、头宽）和转录组谱，以比较改变的分子和疾病途径。基于链长的LC50排名符合预期趋势。PFOA引起多动和PFBA低动，而PFHxA不改变行为。PFOA、PFHxA和PFBA引起的形态和转录组改变对每种化学物质都是独特的，并且是浓度依赖性的，表明不同的毒性机制。癌症是PFOA的主要发病途径，FXR/RXR活化是PFBA的主要途径。此外，暴露于PFOA的斑马鱼的生物学和分子通路的改变与先前流行病学研究和其他动物模型报告的结果相匹配，支持转录组方法的预测价值以及预测与PFHxA或PFBA暴露相关的不良健康结果。
Perfluoroalkyl substances (PFAS) are a class of synthetic chemicals that are persistent in the environment. Due to adverse health outcomes associated with longer chain PFAS, shorter chain chemicals were used as replacements, but developmental toxicity assessments of the shorter chain chemicals are limited. Toxicity of three perfluoroalkyl acids (PFAAs) [perfluorooctanoic acid (PFOA), composed of 8 carbon (C8), perfluorohexanoic acid (PFHxA, C6), and perfluorobutanoic acid (PFBA, C4)] was compared in developing zebrafish (Danio rerio). LC50s at 120 h post fertilization (hpf) assessed potency of each PFAA by exposing developing zebrafish (1–120 hpf) to range of concentrations. Zebrafish were then exposed to sublethal concentrations (0.4–4000 ppb, μg/L) throughout embryogenesis (1–72 hpf). Effects of the embryonic exposure on locomotor activities was completed with the visual motor response test at 120 hpf. At 72 hpf, morphological changes (total body length, head length, head width) and transcriptome profiles to compare altered molecular and disease pathways were determined. The LC50 ranking followed trend as expected based on chain length. PFOA caused hyperactivity and PFBA hypoactivity, while PFHxA did not change behavior. PFOA, PFHxA, and PFBA caused morphological and transcriptomic alterations that were unique for each chemical and were concentration-dependent indicating different toxicity mechanisms. Cancer was a top disease for PFOA and FXR/RXR activation was a top canonical pathway for PFBA. Furthermore, comparison of altered biological and molecular pathways in zebrafish exposed to PFOA matched findings reported in prior epidemiological studies and other animal models, supporting the predictive value of the transcriptome approach and for predicting adverse health outcomes associated with PFHxA or PFBA exposure.
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