| 1. |
- Alvarez-Mora, Iker, et al.
(författare)
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Progress, applications, and challenges in high-throughput effect-directed analysis for toxicity driver identification : is it time for HT-EDA?
- 2024
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Nature. - 1618-2642 .- 1618-2650.
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Forskningsöversikt (refereegranskat)abstract
- The rapid increase in the production and global use of chemicals and their mixtures has raised concerns about their potential impact on human and environmental health. With advances in analytical techniques, in particular, high-resolution mass spectrometry (HRMS), thousands of compounds and transformation products with potential adverse effects can now be detected in environmental samples. However, identifying and prioritizing the toxicity drivers among these compounds remain a significant challenge. Effect-directed analysis (EDA) emerged as an important tool to address this challenge, combining biotesting, sample fractionation, and chemical analysis to unravel toxicity drivers in complex mixtures. Traditional EDA workflows are labor-intensive and time-consuming, hindering large-scale applications. The concept of high-throughput (HT) EDA has recently gained traction as a means of accelerating these workflows. Key features of HT-EDA include the combination of microfractionation and downscaled bioassays, automation of sample preparation and biotesting, and efficient data processing workflows supported by novel computational tools. In addition to microplate-based fractionation, high-performance thin-layer chromatography (HPTLC) offers an interesting alternative to HPLC in HT-EDA. This review provides an updated perspective on the state-of-the-art in HT-EDA, and novel methods/tools that can be incorporated into HT-EDA workflows. It also discusses recent studies on HT-EDA, HT bioassays, and computational prioritization tools, along with considerations regarding HPTLC. By identifying current gaps in HT-EDA and proposing new approaches to overcome them, this review aims to bring HT-EDA a step closer to monitoring applications.
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| 2. |
- Di Paolo, Carolina, et al.
(författare)
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The value of zebrafish as an integrative model in effect-directed analysis : a review
- 2015
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 27:8, s. 1-11
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Forskningsöversikt (refereegranskat)abstract
- Bioassays play a central role in effect-directed analysis (EDA), and their selection and application have to consider rather specific aspects of this approach. Meanwhile, bioassays with zebrafish, an established model organism in different research areas, are increasingly being utilized in EDA. Aiming to contribute for the optimal application of zebrafish bioassays in EDA, this review provides a critical overview of previous EDA investigations that applied zebrafish bioassays, discusses the potential contribution of such methods for EDA and proposes strategies to improve future studies. Over the last 10 years, zebrafish bioassays have guided EDA of natural products and environmental samples. The great majority of studies performed bioassays with embryos and early larvae, which allowed small-scale and low-volume experimental setups, minimized sample use and reduced workload. Biotesting strategies applied zebrafish bioassays as either the only method guiding EDA or instead integrated into multiple bioassay approaches. Furthermore, tiered biotesting applied zebrafish methods in both screening phase as well as for further investigations. For dosing, most of the studies performed solvent exchange of extracts and fractions to dimethyl sulfoxide (DMSO) as carrier. However, high DMSO concentrations were required for the testing of complex matrix extracts, indicating that future studies might benefit from the evaluation of alternative carrier solvents or passive dosing. Surprisingly, only a few studies reported the evaluation of process blanks, indicating a need to improve and standardize methods for blank preparation and biotesting. Regarding evaluated endpoints, while acute toxicity brought limited information, the assessment of specific endpoints was of strong value for bioactivity identification. Therefore, the bioassay specificity and sensitivity to identify the investigated bioactivity are important criteria in EDA. Additionally, it might be necessary to characterize the most adequate exposure windows and assessment setups for bioactivity identification. Finally, a great advantage of zebrafish bioassays in EDA of environmental samples is the availability of mechanism- and endpoint-specific methods for the identification of important classes of contaminants. The evaluation of mechanism-specific endpoints in EDA is considered to be a promising strategy to facilitate the integration of EDA into weight-of-evidence approaches, ultimately contributing for the identification of environmental contaminants causing bioassay and ecological effects.
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