| 1. |
- Audouze, Karine, et al.
(författare)
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Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways : Challenges and Opportunities
- 2021
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- A transformation of regulatory toxicology is underway to meet the demands of testing increasing numbers of chemicals whilst reducing reliance on in vivo models. This transformation requires a shift from chemical safety assessment largely based on direct empirical observation of apical toxicity outcomes in whole organisms to predictive approaches in which outcomes and risks are inferred from accumulated mechanistic understanding.
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| 2. |
- Braeuning, Albert, et al.
(författare)
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Development of new approach methods for the identification and characterization of endocrine metabolic disruptors : a PARC project
- 2023
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Ingår i: Frontiers in Toxicology. - : Frontiers Media SA. - 2673-3080. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action.
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| 3. |
- Moe, Morten K., et al.
(författare)
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The structure of the fire fighting foam surfactant Forafac (R) 1157 and its biological and photolytic transformation products
- 2012
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 89:7, s. 869-875
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Tidskriftsartikel (refereegranskat)abstract
- For several decades, perfluorooctane sulfonate (PFOS) has widely been used as a fluorinated surfactant in aqueous film forming foams used as hydrocarbon fuel fire extinguishers. Due to concerns regarding its environmental persistence and toxicological effects, PFOS has recently been replaced by novel fluorinated surfactants such as Forafac (R) 1157, developed by the DuPont company. The major component of Forafac (R) 1157 is a 6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB), and a link between the trade name and the exact chemical structure is presented here to the scientific community for the first time. In the present work, the structure of the 6:2 FTAB was elucidated by H-1, C-13 and F-19 nuclear magnetic resonance Spectroscopy and high-resolution mass spectrometry. Moreover, its major metabolites from blue mussel (Mytilus edulis) and turbot (Scophthalmus maximus) and its photolytic transformation products were identified. Contrary to what has earlier been observed for PFOS, the 6:2 FTAB was extensively metabolized by blue mussel and turbot exposed to Forafac (R) 1157. The major metabolite was a deacetylated betaine species, from which mono- and di-demethylated metabolites also were formed. Another abundant metabolite was the 6:2 fluorotelomer sulfonamide. In another experiment, Forafac (R) 1157 was subjected to UV-light induced photolysis. The experimental conditions aimed to simulate Arctic conditions and the deacetylated species was again the primary transformation product of 6:2 FTAB. A 6:2 fluorotelomer sulfonamide was also formed along with a non-identified transformation product. The environmental presence of most of the metabolites and transformation products was qualitatively demonstrated by analysis of soil samples taken in close proximity to an airport fire training facility.
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