The new PFAS C6O4 and its effects on marine invertebrates: First evidence of transcriptional and microbiota changes in the Manila clam Ruditapes philippinarum

Bernardini, Ilaria; Matozzo, Valerio; Valsecchi, Sara; Peruzza, Luca; Rovere, Giulia Dalla; Iori, Silvia; Marin, María Gabriella; Fabrello, Jacopo; Ciscato, Maria; Masiero, Laura; Bonato, Marco; Santovito, Gianfranco; Boffo, Luciano; Bargelloni, Luca; Milan, Massimo; Patarnello, Tomaso

doi:10.1016/j.envint.2021.106484

Cited by 43 publications

(22 citation statements)

References 123 publications

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“…However, available in vitro studies show that legacy PFAS compounds exert a cytotoxic effect on the thyroid only at very high concentrations (22). In a context in which studies about cell effects of C6O4 exposure are still scarce (21,29,49,50), only one to date has evaluated the impact of this new generation PFAS on thyroid cells (21), showing a lower toxicity of C6O4 compared with legacy PFAS, mainly PFOA and PFOS, and largely overlapping with our results. In fact, we confirm here the lack of a pro-apoptotic or genotoxic effect of C6O4 on thyreocyetes and add novel data about a possible specific effect on the endocrine pathways related to thyroid function, showing that among long-chain PFAS, PFOA displays a more severe disrupting effect as compared to PFOS and C6O4.…”

Section: Discussionsupporting

confidence: 87%

Comparative Evaluation of the Effects of Legacy and New Generation Perfluoralkyl Substances (PFAS) on Thyroid Cells In Vitro

et al. 2022

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BackgroundPer- and poly-fluorinated alkyl substances (PFAS) are environment-persitent emerging endocrine disrupting chemicals raising health concerns worldwide. Exposure to PFAS has been associated with the imbalance of thyroid hormones. However, available studies addressing the cell mechanism underlying thyroid disrupting feature of legacy PFAS, such as perfluoro-octanoic acid (PFOA), perfluoro-octane-sulfonic acid (PFOS), and the new generation substitutes, such as C6O4, are still lacking. In this study the potential disrupting effect of PFOA, PFOS, and C6O4 on a murine thyroid cell model was assessed.MethodsA rat FRTL-5 cell line was used as the normal thyroid follicular cell model. Cell iodide-uptake, induced by thyroid stimulating hormone (TSH), was used to assess the functional impact of PFAS exposure on cell function. Tetrazolium salt-based cell viability assay and merocyanine 540-based cell staining were used to address the possible involvement of cell toxicity and membrane biophysical properties on altered cell function. The possible direct interaction of PFAS with TSH-receptor (TSH-R) was investigated by computer-based molecular docking and analysis of molecular dynamics. Evaluation of intracellular cAMP levels and gene expression analysis were used to validate the direct impairment of TSH-R-mediated downstream events upon PFAS exposure.ResultsDifferent from PFOS or C6O4, exposure to PFOA at a concentration ≥ 10 ng/mL was associated with significant impairment of the iodide uptake upon TSH stimulation (respectively: basal 100.0 ± 19.0%, CTRL + TSH 188.9 ± 7.8%, PFOA 10 ng/mL + TSH 120.4 ± 20.9%, p= 0.030 vs CTRL + TSH; PFOA 100 ng/mL + TSH 115,6 ± 12,3% p= 0.017 vs CTRL + TSH). No impairment of cell viability or membrane stability was observed. Computational analysis showed a possible direct differential interaction of C6O4, PFOA, and PFOS on a same binding site of the extracellular domain of TSH-R. Finally, exposure to PFOA was associated with a significant reduction of downstream intracellular cAMP levels and both sodium-iodide transporter and thyroperoxidase gene expression upon TSH-R stimulation.ConclusionsOur data suggest that legacy and new generation PFAS can differentially influence TSH dependent signaling pathways through the direct interaction with TSH-R.

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Section: Discussionsupporting

confidence: 87%

Comparative Evaluation of the Effects of Legacy and New Generation Perfluoralkyl Substances (PFAS) on Thyroid Cells In Vitro

et al. 2022

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“…HFPO-DA has been widely encountered in environmental samples [18,20,21] and rarely in human biological samples derived from the general population [14], while DONA has only been detected in surface water [22] and in human plasma samples derived from areas impacted by fluorochemical plants [23]. cC6O4 has recently been found in Italy's largest river basin (Po River, Veneto region, Italy) [24], and it is constantly monitored by regional environmental protection agencies ARPAL [25] and ARPAV [26].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an LC–MS/MS method for the quantitation of 30 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in human plasma, including HFPO-DA, DONA, and cC6O4

et al. 2021

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Per-and polyfluoroalkyl substances (PFASs) include persistent organic pollutants whose spread is still ubiquitous. Efforts to substitute substances of high concern with fluorinated alternatives, such as HFPO-DA (GenX), DONA (ADONA), and cC6O4, have been made. The aim of this work was to develop and validate an isotopic dilution liquid chromatographytandem mass spectrometry (LC-MS/MS) method suitable to quantify 30 PFASs in human plasma. Analytes included legacy PFASs (PFOA, PFOS, and PFHxS), fluorinated alternatives (PFBA, PFBS, 6:2 FTSA, HFPO-DA, DONA, and cC6O4), and newly identified compounds (F-53B and PFECHS). The sample preparation was rapid and consisted of simple protein precipitation and centrifugation. Calibration standards and quality control solutions were prepared with a human pooled plasma containing relatively low background levels of the considered analytes. A complete validation was carried out: the lower limits of quantitation (LLOQs) ranged from 0.009 to 0.245 µg/L; suitable linearity (determination coefficients, R 2 0.989-0.999), precision (2.0-19.5%, relative standard deviation), and accuracy (87.9-113.1% of theoretical) were obtained for considered concentration ranges. No significant variations of analyte responses were recorded under investigated storage conditions and during matrix effect tests. The external verification confirmed the accuracy of the method, although limited to 12 analytes. The method was also applied to 38 human plasma samples to confirm its applicability. The developed assay is suitable for large-scale analyses of a wide range of legacy and emerging PFASs in human plasma. To our knowledge, this is the first published method including cC6O4 for human biomonitoring.

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“…In this regard, one very recent example is represented by a work wherein the long-term effects of the recently introduced compound known as C604 were investigated on the Manila clam (Ruditapes philippinarum) exposed to environmentally relevant concentrations (ranging from 100 ng/L and 1000 ng/L) for 7 and 21 days. Here, the authors observed a number of alterations in the transcription profile of genes involved in the regulation of the immune system, neurodevelopment, protein ubiquitination, cell membrane function, lipid and xenobiotic metabolism, indicating that potential ecotoxic effects and risks for marine organisms might be present in certain areas even after PFOA substitution and phase out [137].…”

Section: Pfas Occurrence In Marine Water and Sedimentsmentioning

confidence: 91%

PFAS Molecules: A Major Concern for the Human Health and the Environment

Panieri

Baralić

Đukić-Ćosić

et al. 2022

Toxics

167

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Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.

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The new PFAS C6O4 and its effects on marine invertebrates: First evidence of transcriptional and microbiota changes in the Manila clam Ruditapes philippinarum

Cited by 43 publications

References 123 publications

Comparative Evaluation of the Effects of Legacy and New Generation Perfluoralkyl Substances (PFAS) on Thyroid Cells In Vitro

Comparative Evaluation of the Effects of Legacy and New Generation Perfluoralkyl Substances (PFAS) on Thyroid Cells In Vitro

Development and validation of an LC–MS/MS method for the quantitation of 30 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in human plasma, including HFPO-DA, DONA, and cC6O4

PFAS Molecules: A Major Concern for the Human Health and the Environment

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