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六氟环氧丙烷二聚酸对斑马鱼(Danio rerio)发育过程中的形态、心脏生理学和基因表达的毒性评估。

Toxicity assessment of hexafluoropropylene oxide-dimer acid on morphology, heart physiology, and gene expression during zebrafish (Danio rerio) development.

机构信息

Boz Life Science Research and Teaching Institute, San Diego, CA, USA.

Division of Extended Studies, University of California San Diego, La Jolla, CA, 92093-0355, USA.

出版信息

Environ Sci Pollut Res Int. 2023 Mar;30(12):32320-32336. doi: 10.1007/s11356-022-24542-z. Epub 2022 Dec 3.

DOI:10.1007/s11356-022-24542-z
PMID:36462083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10017623/
Abstract

Hexafluoropropylene oxide-dimer acid (HFPO-DA) is one of the emerging replacements for the "forever" carcinogenic and toxic long-chain PFAS. HFPO-DA is a polymerization aid used for manufacturing fluoropolymers, whose global distribution and undetermined toxic properties are a concern regarding human and ecological health. To assess embryotoxic potential, zebrafish embryos were exposed to HFPO-DA at concentrations of 0.5-20,000 mg/L at 24-, 48-, and 72-h post-fertilization (hpf). Heart rate increased significantly in embryos exposed to 2 mg/L and 10 mg/L HFPO-DA across all time points. Spinal deformities and edema phenotypes were evident among embryos exposed to 1000-16,000 mg/L HFPO-DA at 72 hpf. A median lethal concentration (LC) was derived as 7651 mg/L at 72 hpf. Shallow RNA sequencing analysis of 9465 transcripts identified 38 consistently differentially expressed genes at 0.5 mg/L, 1 mg/L, 2 mg/L, and 10 mg/L HFPO-DA exposures. Notably, seven downregulated genes were associated with visual response, and seven upregulated genes were expressed in or regulated the cardiovascular system. This study identifies biological targets and molecular pathways affected during animal development by an emerging, potentially problematic, and ubiquitous industrial chemical.

摘要

全氟辛烷磺酸氧化物二聚体酸(HFPO-DA)是一种新兴的“永久性”致癌和有毒长链 PFAS 替代品。HFPO-DA 是一种聚合助剂,用于制造氟聚合物,其在全球的分布和不确定的毒性性质令人担忧,对人类和生态健康构成威胁。为了评估胚胎毒性潜力,将斑马鱼胚胎在受精后 24、48 和 72 小时(hpf)时暴露于 0.5-20000mg/L 的 HFPO-DA 浓度下。在所有时间点,暴露于 2mg/L 和 10mg/L HFPO-DA 的胚胎心率显著增加。在 72 hpf 时,暴露于 1000-16000mg/L HFPO-DA 的胚胎出现脊柱畸形和水肿表型。在 72 hpf 时得出的中位致死浓度(LC)为 7651mg/L。对 9465 个转录本进行的浅层 RNA 测序分析表明,在 0.5mg/L、1mg/L、2mg/L 和 10mg/L HFPO-DA 暴露下,有 38 个基因持续差异表达。值得注意的是,七个下调基因与视觉反应有关,七个上调基因在心血管系统中表达或受其调控。本研究确定了在动物发育过程中受一种新兴的、潜在有问题的和普遍存在的工业化学品影响的生物靶标和分子途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/1136f0cc96ce/11356_2022_24542_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/d9f3a214dfa4/11356_2022_24542_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/d29dd7d5a776/11356_2022_24542_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/a646ed09ef1f/11356_2022_24542_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/d375f4bdf122/11356_2022_24542_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/5cd0a0c0b915/11356_2022_24542_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/1136f0cc96ce/11356_2022_24542_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/d9f3a214dfa4/11356_2022_24542_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/d29dd7d5a776/11356_2022_24542_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/a646ed09ef1f/11356_2022_24542_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/d375f4bdf122/11356_2022_24542_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/5cd0a0c0b915/11356_2022_24542_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4abd/10017623/1136f0cc96ce/11356_2022_24542_Fig6_HTML.jpg

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