Sandra Verstraelen - Academia.edu (original) (raw)

Papers by Sandra Verstraelen

The EMBO Journal, 2022

The use of animals in neuroscience and biomedical research remains controversial. Policy is built... more The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the “3R” principle of “Refining, Reducing and Replacing” animal experiments, and across the globe, different initiatives stimulate the use of animal‐free methods. Based on an extensive literature screen to map the development and adoption of animal‐free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal‐derived models. Among the animal‐free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal‐free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non‐animal‐based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal‐free approaches.

article i nfo + progenitor-derived dendritic cells THP-1 monocytes THP-1 macrophages Early detect... more article i nfo + progenitor-derived dendritic cells THP-1 monocytes THP-1 macrophages Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin...

Toxicology Letters, 2017

[Verstraelen, Sandra; Jacobs, An; Wathiong, Bart; Deville, Sarah; Nelissen, Inge] Flemish Inst Te... more [Verstraelen, Sandra; Jacobs, An; Wathiong, Bart; Deville, Sarah; Nelissen, Inge] Flemish Inst Techn Res, Dept Hlth, Mol, Belgium. [Wathiong, Bart; Deville, Sarah] Hasselt Univ, Biomed Res Inst, Diepenbeek, Belgium. [Pelaz, Beatriz; Moliman, Mahmoud Gamal Mohamed; Parak, Wolfgang] Philipps Univ Marburg, Fachbereich Phys, Marburg, Germany. [Gutleb, Arno; Serchi, Tommaso] Luxembourg Inst Sci & Technol, Environm Res & Innovat Dept, Luxembourg, Luxembourg. [Vandebriel, Rob] Natl Inst Publ Hlth & Environm, Bilthoven, Netherlands.

Journal of Analytical Atomic Spectrometry, 2021

In this review we discuss the novel developments in mass spectrometry-based analytical methods fo... more In this review we discuss the novel developments in mass spectrometry-based analytical methods for size determination, chemical identification, and quantification of the microplastic and nanoplastic in indoor air and dust.

MethodsX, 2020

In vitro-based new approach methodologies (NAMs) provide a pragmatic solution to animal testing o... more In vitro-based new approach methodologies (NAMs) provide a pragmatic solution to animal testing of petroleum substances and their constituents. A previous study exposed an in vitro model (A549 cells) at the air-liquid interface (ALI) to assess inhalation toxicity of a single compound, ethylbenzene. Experimental conditions using VITROCELL R 24/48 exposure system were optimized to achieve a deposition efficiency that resulted in dosedependent biological changes. The feasibility of this setup was evaluated for testing the complex substance gasoline, which, at only high concentrations, can induce mild respiratory irritation in animals and cough in humans. • Results showed that perpendicular ALI exposure flow systems (VITROCELL® 6/4 and 24/48) may not be appropriate for testing gasoline because it was not possible to achieve enough deposition onto the cells and in the culture medium to measure dose and to determine dose-dependent biological changes (more information can be found in 'Supplementary material and/or Additional information' section). • Structural features (e.g. aromatic or saturated hydrocarbon structure) and high hydrophobicity, together with the low concentrations of individual components in gasoline, may have caused the low deposition. • To achieve a higher deposition on the cells, A549 cells were exposed to gasoline at the ALI by passive dosing. The results demonstrate that the presented methodology is a promising NAM for inhalation toxicity testing of (semi-)volatile complex substances with low aqueous solubility.

Toxicology Letters, 2018

over 6 kPa (25 • C). Possible reason why these substances are not part of applicability domain is... more over 6 kPa (25 • C). Possible reason why these substances are not part of applicability domain is due to volatilization of substance during test solution preparation or exposure. The standard protocol employs saline as the solvent and the reduction of the highly volatile substances in solvent may lead to the false negatives. Mineral oil has the potential to lower the volatilization rate of the test substances compared to saline. We evaluated the ability of mineral oil to be a better solvent for highly volatile substances. Highly volatile substances, which GHS classification was assigned to, were correctly evaluated without false negatives by the modification of the solvent to mineral oil. The predictive performance was improved from the accuracy 75.0% (15/20), the false positive rate 7.7% (1/13) and the false negative rate 57.1% (4/7) to the accuracy 95.0% (19/20), the false positive rate 7.7% (1/13), and the false negative rate 0% (0/7) respectively. Furthermore, the predictive performance was verified including highly volatile substances by the modification of the protocol. The substance dataset was constructed in reference to STE Summary Review Document by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM, 2013) and the Draize eye test Reference database by Barroso et al. (2017). As a result, the accuracy 86.6% (194/224), the false positive rate 18.8% (27/144), and the false negative rate 3.8% (3/80) were obtained. In conclusion, the STE test method is suitable for testing the GHS NC substances.

Journal of Applied Toxicology, 2016

Zebrafish phenotypic assays have shown promise to assess human hepatotoxicity, though scoring of ... more Zebrafish phenotypic assays have shown promise to assess human hepatotoxicity, though scoring of liver morphology remains subjective and difficult to standardize. Liver toxicity in zebrafish larvae at 5 days was assessed using gene expression as the biomarker approach, complementary to phenotypic analysis and analytical data on compound uptake. This approach aimed to contribute to improved hepatotoxicity prediction, with the goal of identifying biomarker(s) as a step towards the development of transgenic models for prioritization. Morphological effects of hepatotoxic compounds (acetaminophen, amiodarone, coumarin, methapyrilene and myclobutanil) and saccharin as the negative control were assessed after exposure in zebrafish larvae. The hepatotoxic compounds induced the expected zebrafish liver degeneration or changes in size, whereas saccharin did not have any phenotypic adverse effect. Analytical methods based on liquid chromatography-mass spectrometry were optimized to measure stability of selected compounds in exposure medium and internal concentration in larvae. All compounds were stable, except amiodarone for which precipitation was observed. There was a wide variation between the levels of compound in the zebrafish larvae with a higher uptake of amiodarone, methapyrilene and myclobutanil. Detection of hepatocyte markers (CP, CYP3A65, GC and TF) was accomplished by in situ hybridization of larvae to coumarin and myclobutanil and confirmed by real-time reverse transcription-quantitative polymerase chain reaction. Experiments showed decreased expression of all markers. Next, other liver-specific biomarkers (i.e. FABP10a and NR1H4) and apoptosis (i.e. CASP-3 A and TP53) or cytochrome P450-related (CYP2K19) and oxidoreductase activity-related (ZGC163022) genes, were screened. Links between basic mechanisms of liver injury and results of biomarker responses are described.

Toxicology in vitro : an international journal published in association with BIBRA, 2008

This review first describes the mechanism and cell types involved in allergic asthma, which is a ... more This review first describes the mechanism and cell types involved in allergic asthma, which is a complex clinical disease characterized by airway obstruction, airway inflammation and airway hyperresponsiveness to a variety of stimuli. The development of allergic asthma exists of three phases, namely the induction phase, the early-phase asthmatic reaction (EAR) and the late-phase asthmatic reaction (LAR). In the induction phase, antigen-presenting cells play a major role. Most important cells in the EAR are mast cells, and during the LAR, various cell types, such as eosinophils, neutrophils, T cells, macrophages, dendritic cells (DCs), and cells that endow structure are involved. In occupational asthma, this immunological mechanism is involved in 90% of the cases. The second part of this review gives an overview of in vitro models to assess the hazardous potential of high- and low-molecular weight chemicals on the respiratory system. In order to develop a good in vitro model for resp...

Experientia Supplementum, 2012

Chemical sensitization remains an important environmental and occupational health issue. A wide r... more Chemical sensitization remains an important environmental and occupational health issue. A wide range of substances have been shown to possess the ability to induce skin sensitization or respiratory sensitization. As a consequence, there is a need to have appropriate methods to identify sensitizing agents. Although a considerable investment has been made in exploring opportunities to develop methods for hazard identification and characterization, there are, as yet, no validated nonanimal methods available. A state of the art of the different in vitro approaches to identify contact and respiratory capacity of chemicals is covered in this chapter.

Toxicology Letters, 2009

There are currently no accepted biological prediction models for assessing the potential of a sub... more There are currently no accepted biological prediction models for assessing the potential of a substance to cause respiratory sensitization. New tests should be based on mechanistic understanding and should be preferentially restricted to in vitro assays. The major goal of this study was to investigate the alterations in gene expression of human alveolar epithelial (A549) cells after exposure to respiratory sensitizing and non-respiratory sensitizing chemicals, and to identify genes that are able to discriminate between both groups of chemicals. A549 cells were exposed during 6, 10, and 24 h to the respiratory sensitizers ammonium hexachloroplatinate IV, hexamethylene diisocyanate, and trimellitic anhydride, the irritants acrolein and methyl salicylate, and the skin sensitizer 1-chloro-2,4-dinitrobenzene. Overall changes in gene expression were evaluated using Agilent Whole Human Genome 4x44K oligonucleotide arrays. A Fisher linear discriminant analysis was used to obtain a ranking of genes that reflects their potential to discriminate between respiratory sensitizing and respiratory non-sensitizing chemicals. Among the 20 most discriminating genes, which were categorized into molecular and biological gene ontology (GO) terms, CTLA4 could be associated with asthma and/or respiratory sensitization. When categorizing the top-1000 genes into biological GO terms, 22 genes were associated with immune function. Using a pathway analysis tool to identify possible underlying mechanisms of respiratory sensitization, no known canonical signaling pathway was observed to be activated in the A549 cell line.

Toxicology Letters, 2008

People interested in the research are advised to contact the author for the final version of the ... more People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

Toxicology in Vitro, 2014

For the classification of respiratory sensitizing chemicals, no validated in vivo nor in vitro te... more For the classification of respiratory sensitizing chemicals, no validated in vivo nor in vitro tests are currently available. In this study, we evaluated whether respiratory sensitizers trigger specific signals in human bronchial epithelial (BEAS-2B) cells at the level of the transcriptome. The cells were exposed during 6, 10, and 24 h to 4 respiratory sensitizers and 6 non-respiratory sensitizers (3 skin sensitizers and 3 respiratory irritants) at a concentration inducing 20% cell viability loss after 24 h. Changes in gene expression were evaluated using Agilent Whole Human Genome 4 Â 44 K oligonucleotide arrays. A limited number of 11 transcripts could be identified as potential biomarkers to identify respiratory sensitizers. Three of these transcripts are associated to immune system processes (HSPA5, UPP1, and SEPRINE1). In addition, the transcriptome was screened for transcripts that are differentially expressed compared to vehicle control for each chemical. The results show that the NRF2-mediated oxidative stress response is activated in the cell line after stimulation with all of the chemicals that were selected in our study, and that-at the level of gene expression-this pathway shows no potential to discriminate between any of the three compound groups: respiratory sensitizers, skin sensitizers, or electrophilic respiratory irritants.

Toxicology in Vitro, 2009

It is recognized that respiratory sensitization is a hazard of high concern. Despite internationa... more It is recognized that respiratory sensitization is a hazard of high concern. Despite international regulatory requirements there is no established protocol for the identification of chemical respiratory sensitizers. New tests should be based on mechanistic understanding and should be preferentially restricted to in vitro assays. The major goal of this study was to investigate the genetic response of human THP-1 macrophages after contact with respiratory (non-)sensitizers, and to identify genes that are able to discriminate between both groups. THP-1 macrophages were exposed during different time points to 3 respiratory sensitizers, 2 irritants, and 1 skin sensitizer. Gene expression changes were evaluated using Agilent Whole Human Genome arrays. Fisher Linear Discriminant Analysis was used to obtain a ranking of genes that reflects their potential to discriminate between respiratory (non-)sensitizing chemicals. Among the 20 most discriminating genes which were categorized into molecular and biological Gene Ontology (GO) terms, EIF4E, PDGFRB, SEMA7A, and ZFP36L2 could be associated with respiratory sensitization. When categorizing the top-1000 genes into biological GO terms, 24 genes were associated with immune function. Using a pathway analysis tool, platelet-derived growth factor signaling was observed to be activated in THP-1 macrophages in the context of respiratory sensitization.

Toxicology in Vitro, 2008

Occupational exposure to chemicals is one of the main causes of respiratory allergy and asthma. I... more Occupational exposure to chemicals is one of the main causes of respiratory allergy and asthma. Identification of chemicals that trigger allergic asthma is difficult as underlying processes and specific markers have not yet been clearly defined. Moreover, adequate classification of the respiratory toxicity of chemicals is hampered due to the lack of validated in vivo and in vitro test methods. The study of differential gene expression profiles in appropriate human in vitro cell systems is a promising approach to identify selective markers for respiratory allergy. As alveolar macrophages display important immunological and inflammatory properties in response to foreign substances in the lung, we aimed at gaining more insight in changes of human macrophages transcriptome and to identify selective genetic markers for respiratory sensitization in response to hexamethylene diisocyanate (HDI). In vitro cultures of human THP-1 cells were differentiated into macrophages and exposed to 55 lg/ml HDI for 6 and 10 h. Using human oligonucleotide microarrays, changes were observed in the expression of genes that are involved in diverse biological and molecular processes, including detoxification, oxidative stress, cytokine signaling, and apoptosis, which can lead to the development of asthma. These genes are possible markers for respiratory sensitization caused by isocyanates.

Toxicology in Vitro, 2011

Respiratory sensitization provides a case study for a new approach to chemical safety evaluation,... more Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/ or human experimental/predictive models are not currently available. Therefore, the goal of a working group was to design a road map to develop an ASAT approach for respiratory sensitisers. This approach should aim at (i) creating a database on respiratory functional biology and toxicology, (ii) applying data analyses to understand the multi-dimensional sensitization response, and how this predisposes to respiratory inflammation and irritation, and (iii) building a systems model out of these analyses, adding pharmacokinetic-pharmacodynamic modeling to predict respiratory responses to low levels of sensitisers. To this end, the best way forward would be to follow an integrated testing approach. Experimental research should be targeted to (i) QSAR-type approaches to relate potential as a respiratory sensitizer to its chemical structure, (ii) in vitro models and (iii) in vitro-in vivo extrapolation/validation.