Key Takeaways & Executive Findings
- •• • PFOS exposure induced 61 differential metabolites in zebrafish embryos, while 6:2 FTSA induced 33, indicating a distinct metabolic perturbation profile; the higher count for PFOS suggests a broader metabolic disruption, which is critical for risk assessment of PFOS alternatives. • • Both PFOS and 6:2 FTSA caused embryonic malformations after 72 h exposure, confirming developmental toxicity; this underscores the need for thorough toxicological screening of replacement compounds. • • PFOS primarily disrupted lipid metabolism pathways, leading to immunotoxicity, whereas 6:2 FTSA affected dopaminergic synapse pathways, indicating neurotoxicity; these pathway-specific effects are essential for understanding mechanisms of toxicity. • • The identified differential metabolites were predominantly lipids and amino acid derivatives, providing a biochemical basis for the observed phenotypic effects; this information can guide targeted biomarker development for environmental monitoring.
Abstract
Perfluorooctane sulfonate (PFOS), a typical perfluorinated compound, has been restricted from production and use due to its adverse effects on organisms and ecosystems. It has been replaced by various emerging alternatives, including 6:2 fluorotelomer sulfonic acid (6:2 FTSA). Recently, 6:2 FTSA has been widely detected in aquatic environments; however, studies on its toxicity to aquatic organisms remain limited. To compare the toxic effects of PFOS and 6:2 FTSA on aquatic organisms, zebrafish embryos were exposed to each compound for 72 h. Toxic effects were evaluated, and alterations in endogenous metabolites and metabolic pathways in zebrafish embryos were analyzed using metabolomics. The study demonstrated that both PFOS and 6:2 FTSA induced malformations in zebrafish embryos, with 61 and 33 endogenous differential metabolites identified respectively, predominantly involving lipids and amino acid derivatives. PFOS induces immunotoxicity primarily by disrupting lipid metabolism pathways, thereby interfering with normal embryonic development. In addition, 6:2 FTSA exhibited neurotoxicity by affecting metabolic pathways such as dopaminergic synapses. This study elucidates the differential metabolic responses induced by PFOS and 6:2 FTSA in zebrafish embryos, providing a theoretical basis for assessing the health risks of PFOS alternatives.
1. Introduction
Perfluorooctane sulfonate (PFOS) has been widely used in industrial and consumer products due to its surfactant properties and chemical stability. However, its persistence, bioaccumulation, and toxicity have led to global restrictions, prompting the introduction of alternative compounds such as 6:2 fluorotelomer sulfonic acid (6:2 FTSA). While 6:2 FTSA is now frequently detected in aquatic environments, its toxicological profile remains inadequately characterized, particularly regarding metabolic effects in aquatic organisms.
This study addresses the critical gap by employing untargeted metabolomics to compare the metabolic responses of zebrafish embryos exposed to PFOS and 6:2 FTSA. By identifying differential metabolites and affected pathways, the research provides mechanistic insights into the distinct toxicities of these compounds, which is essential for evaluating the safety of PFOS substitutes and informing regulatory decisions.
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XIE Ting, ZHANG Jing, WANG Qiang, CHEN Meng (2026). Metabolomics Study of Zebrafish Embryos Exposed to PFOS and 6:2 FTSA. Environmental Chemistry. https://doi.org/10.7524/j.issn.0254-6108.2025022301
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Frequently Asked Questions
What are the specific metabolic pathways disrupted by PFOS and 6:2 FTSA in zebrafish embryos?
PFOS primarily disrupts lipid metabolism pathways, leading to immunotoxicity, while 6:2 FTSA affects dopaminergic synapse pathways, indicating neurotoxicity. These findings are based on metabolomic analysis of 61 and 33 differential metabolites, respectively.
How do the numbers of differential metabolites compare between PFOS and 6:2 FTSA, and what does this imply?
PFOS induced 61 differential metabolites, whereas 6:2 FTSA induced 33. The higher number for PFOS suggests a broader metabolic disruption, which may correlate with its known higher toxicity and bioaccumulation potential.
What is the significance of the 72-hour exposure period in this study?
The 72-hour exposure period covers the embryonic development phase of zebrafish, allowing observation of malformations and metabolic changes during critical organogenesis. This timeframe is standard for developmental toxicity studies and enables comparison with other research.
Can the identified differential metabolites serve as biomarkers for PFOS and 6:2 FTSA exposure?
Yes, the predominant classes of differential metabolites (lipids and amino acid derivatives) could potentially serve as biomarkers. However, further validation in field samples and other species is required to establish their reliability.
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