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As a Chinese-specific alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the metal plating industry for over 40 years. This prevalence of use has resulted in its subsequent detection within the environment, wildlife, and humans. Despite this, however, its hepatotoxic effects on aquatic organisms remain unclear. Here, we characterized the impacts of long-term F-53B exposure on adult zebrafish liver and their offspring. Results showed that the concentration of F-53B was greater in the F0 liver than that in the gonads and blood. Furthermore, males had significantly higher liver F-53B levels than females. Hepatomegaly and obvious cytoplasmic vacuolation indicated that F-53B exposure induced liver injury. Compared to control, liver triglyceride levels decreased by 30% and 33.5% in the 5 and 50 μg/L-exposed males and 22% in 50 μg/L-exposed females. Liver transcriptome analysis of F0 adult fish found 2175 and 1267 differentially expressed genes (DEGs) in the 5 μg/L-exposed males and females, respectively. Enrichment analyses further demonstrated that the effects of F-53B on hepatic transcripts were sex-dependent. Gene Ontology showed that most DEGs were involved in multicellular organism development in male fish, whereas in female fish, most DEGs were related to metabolic processes and gene expression. qRT-PCR analysis indicated that the PPAR signaling pathway likely contributed to F-53B-induced disruption of lipid metabolism in F0 adult fish. In F1 larvae (5 days post fertilization), the transcription of pparα increased, like that in F0 adult fish, but most target genes showed the opposite expression trends as their parents. Taken together, our research demonstrated chronic F-53B exposure adversely impacts zebrafish liver, with disruption of PPAR signaling pathway dependent on sex and developmental stage. Image 1 • Accumulation of F-53B in zebrafish liver is sex-dependent. • F-53B exposure induces hepatomegaly and decreases liver triglyceride levels. • F-53B exposure results in differences between male and female hepatic transcripts. • F-53B interferes with the PPAR signal pathway in adult fish and their offspring. Long-term F-53B exposure induced hepatomegaly and disrupted lipid metabolism in F0 adult zebrafish and disturbed the transcriptional levels of genes involved in the PPAR signaling pathway in F1 larvae. [ABSTRACT FROM AUTHOR]

Abstract As an alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the Chinese chrome plating industry for over four decades. It has been increasingly detected in environmental matrices in recent years, causing great concern regarding its potential health risks to humans and wildlife. However, its adverse effects on biota remain largely unknown. To explore the chronic toxicity of F-53B on reproduction, a two-generational study was conducted using zebrafish (Danio rerio). Adult zebrafish (F0 generation) were chronically exposed to different concentrations of F-53B (0, 5, 50, and 500 μg/L) for 180 d using a flow-through exposure system, with F1 and F2 generations reared without exposure. The reproductive toxicity endpoints were assessed in F0 and F1 adult fish. Results showed that F-53B accumulated in the F0 gonads and transferred to the F1 generation via maternal eggs, and even remained in F1 adult fish and their eggs (F2) after 180 d depuration. In the F0 generation, F-53B exposure significantly inhibited growth and induced reproductive toxicity, including decreased gonadosomatic index and egg production/female, changes in the histological structure of the gonads, and increased serum testosterone levels. In particular, serum estradiol and vitellogenin levels were significantly increased in 5 μg/L F-53B-exposed adult males. The transcriptional levels of several genes along the hypothalamic-pituitary-gonadal axis were altered in F0 generation fish. Testis transcriptome analysis revealed that F-53B exposure disrupted spermatogenesis in F0 male zebrafish. Maternal transfer of F-53B also induced adverse effects on growth and reproduction in the F1 generation. Furthermore, the higher occurrence of malformation and lower survival in F1 and F2 embryos indicated that parental exposure to F-53B could impair the embryonic development of offspring. Taken together, this study demonstrated that F-53B could induce reproductive toxicity in zebrafish similar to that induced by legacy PFOS, and its potential adverse effects on offspring deserve further investigation. Graphical abstract Image 1 Highlights • Bioconcentration of F-53B was gender-dependent, and transfer from parent to eggs. • Similar to PFOS, F-53B exposure inhibited the growth and reproduction of zebrafish. • F-53B exposure altered sex hormone level and expression of genes along HPGL axis. • Transcriptome analysis showed F-53B exposure disrupted spermatogenesis in male fish. • Parental exposure to F-53B could impair embryonic development of offspring. Long-term exposure to F-53B for one generation had adverse effects on reproduction in both F0 and F1 adult fish and impaired embryonic development of offspring. [ABSTRACT FROM AUTHOR]

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 12 mg/L) from 6 to 132 h 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 12 mg/L F-53B-treated groups at 132 hpf. Continuous exposure to 3 mg/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. [ABSTRACT FROM AUTHOR]

Abstract Although 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), an alternative to perfluorooctanesulfonate (PFOS), has been regularly detected in different environmental matrices, information regarding its toxicity remains limited. To explore the transgenerational thyroid-disrupting capacity of F-53B, adult zebrafish (F0) were exposed to different concentrations of F-53B (0, 5, 50, or 500 μg/L) for 180 d, with their offspring (F1 and F2) subsequently reared in uncontaminated water. Thyroid disturbances were then examined in the three (F0, F1, and F2) generations. For F0 adult fish, thyroxine (T4) increased in both sexes after exposure to 50 μg/L F-53B, whereas 3,5,3′-triiodothyronine (T3) decreased in all groups, except for 50 μg/L F-53B-treated males. For F1 embryos, parental exposure resulted in F-53B transfer as well as an increase in T4 content. At 5 days post-fertilization, the significant increase in T4 and decrease in T3 were accompanied by a decrease in body length, increase in mortality, and increase in uninflated posterior swim bladder occurrence in F1 larvae. Although thyroid hormone levels were not changed significantly in F1 adult fish or F2 offspring compared with the control, the transcription levels of several genes along the hypothalamus-pituitary-thyroid axis were significantly modified. Our study demonstrated that F-53B possesses transgenerational thyroid-disrupting capability in zebrafish, indicating it might not be a safer alternative to PFOS. Graphical abstract Unlabelled Image Highlights • F-53B exposure disrupted the balance of thyroid hormone levels in F0 adult fish. • Increased T4 levels in F1 eggs were consistent with the T4 level of F0 female serum. • Parental exposed to F-53B altered THs and the HPT axis genes expression in F1 larvae. • Change of TH levels companied with defected swim bladder in F1 larvae. • The change of some HPT axis genes expression still present in F1 adult and F2 larvae. [ABSTRACT FROM AUTHOR]

Experimental studies suggested per- and polyfluoroalkyl substances (PFASs) may disrupt estrogens in animals, however, the epidemiological evidence on the associations of PFASs with estrogens is sparse. We investigated the associations of legacy PFASs and their alternatives, including F-53B, the perfluorooctane sulfonate (PFOS) replacement that is specifically and commonly used in China, with estrogen concentrations in newborns. We quantified six PFASs and three estrogens in the cord sera of 942 newborns from a birth cohort in Wuhan, China, between 2013 and 2014. After adjusting for confounders and correcting for multiple comparisons, we observed that both legacy PFASs and their alternatives were associated with higher serum levels of estradiol (E2). Some of the PFASs were associated with increasing levels of estrone (E1) and estriol (E3). Analysis of PFASs in mixture using weighted quantile sum regressions showed that F-53B contributed 20.1% and 48.5% to the associations between PFASs and E1 and E2, respectively. This study provided epidemiological data on the associations between common PFAS exposures and estrogens in newborns. Additional toxicology studies are needed to fully understand the effects of PFASs on estrogens and the mechanisms. ga1 • 6:2 Cl-PFESA, trade name F-53B, is a PFOS alternative specifically used in China. • 6:2 Cl-PFESA has ranked as 3rd highest PFASs exposed Chinese neonates. • Associations between 6 PFASs and 3 estrogen levels in neonates were assessed. • Both legacy PFASs and the alternatives were related to higher estrogen levels in cord sera. • 6:2 Cl-PFESA weighted more than PFOS and PFOA in association with estradiol in neonates. [ABSTRACT FROM AUTHOR]