title: 6:2 Chlorinated polyfluorinated ether sulfonate, a PFOS alternative, induces embryotoxicity and disrupts cardiac development in zebrafish embryos.
abstract: As an alternative to perfluorooctanesulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used as a mist suppressant in Chinese electroplating industries for over 30 years. It has been found in the environment and fish, and one acute assay indicated F-53B was moderately toxic. However, the toxicological information on this compound was incomplete and insufficient for assessment of their environment impact. The object of this study was to examine the developmental toxicity of F-53B using zebrafish embryos. Zebrafish embryos were incubated in 6-well plates with various concentrations of F-53B (1.5, 3, 6, and 12mg/L) from 6 to 132h post fertilization (hpf). Results showed that F-53B exposure induced developmental toxicity, including delayed hatching, increased occurrence of malformations, and reduced survival. Malformations, including pericardial and yolk sac edemas, abnormal spines, bent tails, and uninflated swim bladders, appeared at 84 hpf, and increased with time course and dose. A decrease in survival percentages was noted in the 6 and 12mg/L F-53B-treated groups at 132 hpf. Continuous exposure to 3mg/L F-53B resulted in high accumulation levels in zebrafish embryos, suggesting an inability for embryos to eliminate this compound and a high cumulative risk to fish. We also examined the cardiac function of embryos at specific developmental stages following exposure to different concentrations, and found that F-53B induced cardiac toxicity and reduced heart rate. Even under low F-53B concentration, o-dianisidine staining results showed significant decrease of relative erythrocyte number at 72 hpf before the appearance of observed effects of F-53B on the heart. To elucidate the underlying molecular changes, genes involved in normal cardiac development were analyzed using real-time qPCR in the whole-body of zebrafish embryos. F-53B inhibited the mRNA expression of β-catenin (ctnnb2) and wnt3a. The mRNA levels of β-catenin targeted genes (nkx2.5 and sox9b), which play critical roles in cardiogenesis, were also reduced after exposure. Thus, exposure to F-53B impaired the development of zebrafish embryos and disrupted cardiac development, which might be mediated by effects on the Wnt signaling pathway and decrease of erythrocyte numbers.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Shi
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sheng
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Sun
authors.affiliation: Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address: daijy@ioz.ac.cn.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D000476:Alkanesulfonates / Q000737:chemistry / Q000633:toxicity*; D017738:Alkanesulfonic Acids / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D005466:Fluorocarbons / Q000737:chemistry / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D007814:Larva / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C588014:2-((6-chloro-1,1,2,2,3,3,4,4,5,5,6,6-dodecafluorohexyl)oxy)-1,1,2,2-tetrafluoroethanesulfonic acid; D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C076994:perfluorooctane sulfonic acid
keywords: Cardiac development; Developmental toxicity; F-53B; Wnt signaling pathway; Zebrafish