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Miriam N Jacobs, Rosemary J Versteegen, Carol Treasure, Jennifer Murray
The number and scope of Organisation for Economic Cooperation and Development (OECD) in vitro test guidelines (TGs) are increasing, in an effort to both improve human relevance and replace in vivo animal testing.  In vitro test methods being developed for TG use are increasing the use of human based reagents, in combination with, or replacing animal derived reagents, and demand for human reagents is likely to grow in the near future.  There are a range of issues associated with the ethical use of human reagents, particularly human serum, in the adaptation and development of in vitro TGs, especially to ensure that there is no human exploitation, legal requirements are adhered to, and that the origin of the reagent is assured...
February 19, 2019: ALTEX
Diego Marescotti, Tommaso Serchi, Karsta Luettich, Yang Xiang, Elisa Moschini, Marja Talikka, Florian Martin, Karine Baumer, Remi Dulize, Dariusz Peric, David Bornand, Emmanuel Guedj, Alain Sewer, Sebastian Cambier, Servane Contal, Aline Chary, Arno C Gutleb, Stefan Frentzel, Nikoloai V Ivanov, Manuel C Peitsch, Julia Hoeng
To more accurately model inhalation toxicity in vitro, we developed a tetra-culture system that combines lung alveolar epithelial cells, endothelial cells, macrophages, and mast cells in a three-dimensional orientation. We characterized the influence of the added complexity using network perturbation analysis and gene expression data. This will allow us to gain insight into the steady-state profile of the assembled, complete three-dimensional model using all four cell types and of simpler models of one, two, or three cell types...
February 12, 2019: ALTEX
George Helman, Imran Shah, Antony J Williams, Jeff Edwards, Jeremy Dunne, Grace Patlewicz
Generalized Read-Across (GenRA) is a data driven approach which makes read-across predictions on the basis of a similarity weighted activity of source analogues (nearest neighbors). GenRA has been described in more detail in the literature (Shah et al., 2016; Helman et al., 2018). Here we present its implementation within the EPA's CompTox Chemicals Dashboard to provide public access to a GenRA module structured as a read-across workflow. GenRA assists researchers in identifying source analogues, evaluating their validity and making predictions of in vivo toxicity effects for a target substance...
February 4, 2019: ALTEX
Haojian Li, Jing Bai, Guorui Zhong, Haosi Lin, Changsheng He, Renke Dai, Hongli Du, Lizhen Huang
Since the EU banned animal testing for cosmetic products and ingredients in 2013, many defined approaches (DA) for skin sensitization assessment have been developed. Machine learning models were shown to be effective in DAs, but the predictivity might be affected by data imbalance (i.e. more numbers of sensitizers than non-sensitizers) and limited information in the databases. To improve the predictivity of DAs, here we attempted to apply data-rebalancing ensemble learning (bagging with support vector machine (SVM)) and a novel and comprehensive Cosmetics Europe database...
January 23, 2019: ALTEX
Christy M Foran, Taylor Rycroft, Jeffrey Keisler, Edward J Perkins, Igor Linkov, Natàlia Garcia-Reyero
The adverse outcome pathway (AOP) framework is a conceptual construct that mechanistically links molecular initiating events to adverse biological outcomes through a series of causal key events (KEs) that represent the perturbation of the biological system. Quantitative, predictive AOPs are necessary for screening emerging contaminants and potential substitutes to inform their prioritization for testing. In practice, they are not widely used because they can be costly to develop and validate. A modular approach for assembly of quantitative AOPs, based on existing knowledge, would allow for rapid development of biological pathway models to screen contaminants for potential hazards and prioritize them for subsequent testing and modeling...
January 20, 2019: ALTEX
Mario Beilmann, Harrie Boonen, Andreas Czich, Gordon Dear, Philip Hewitt, Tomas Mow, Peter Newham, Teija Oinonen, Francois Pognan, Adrian Roth, Jean-Pierre Valentin, Freddy Van Goethem, Richard J Weaver, Barbara Birk, Scott Boyer, Francesca Caloni, Alice E Chen, Raffaella Corvi, Mark T D Cronin, Mardas Daneshian, Lorna C Ewart, Rex E Fitzgerald, Geraldine A Hamilton, Thomas Hartung, Joshua D Kangas, Nynke I Kramer, Marcel Leist, Uwe Marx, Sebastian Polak, Costanza Rovida, Emanuela Testai, Bob Van der Water, Paul Vulto, Thomas Steger-Hartmann
Investigative Toxicology describes the de-risking and mechanistic elucidation of toxicities, supporting early safety decisions in the pharmaceutical industry. Recently, Investigative Toxicology has contributed to a shift in pharmaceutical toxicology, from a descriptive to an evidence-based, mechanistic discipline. This was triggered by high costs and low throughput of Good Laboratory Practice in vivo studies, and increasing demands for adhering to the 3R (Replacement, Reduction and Refinement) principles of animal welfare...
December 20, 2018: ALTEX
Richard S Judson, Russell S Thomas, Nancy Baker, Anita Simha, Xia Meng Howey, Carmen Marable, Nicole C Kleinstreuer, Keith A Houck
Instilling confidence in use of in vitro assays for predictive toxicology requires evaluation of assay performance. Performance is typically assessed using reference chemicals--compounds with defined activity against the test system target. However, developing reference chemical lists has historically been very resource-intensive. We developed a semi-automated process for selecting and annotating reference chemicals across many targets in a standardized format and demonstrate the workflow here. A series of required fields defines the potential reference chemical: the in vitro molecular target, pathway, or phenotype affected; and the chemical's mode (e...
December 17, 2018: ALTEX
Miriam Pons, Georg Nagel, Yanira Zeyn, Mandy Beyer, Teresa Laguna, Tina Brachetti, Andreas Sellmer, Siavosh Mahboobi, Roland Conradi, Falk Butter, Oliver H Krämer
Experiments with cultured mammalian cells represent an in vitro alternative to animal experiments. Fetal calf serum (FCS) is the most commonly used media supplement worldwide. FCS contains a mixture of largely undefined growth factors and cytokines, which support cell proliferation. This undefined nature of FCS is a source of experimental variation, undesired immune responses, possible contaminations, and because of its way of production an ethical concern. Thus, alternative, defined, valid, and reliable media supplements should be characterized in a large number of experiments...
December 14, 2018: ALTEX
Lenny Kamelia, Sylvia Brugman, Laura de Haan, Hans B Ketelslegers, Ivonne M C M Rietjens, Peter J Boogaard
The present study evaluates the applicability of the zebrafish embryotoxicity test (ZET) to assess prenatal developmental toxicity (PDT) potency of the DMSO-extracts of 9 petroleum substances (PS), with variable polycyclic aromatic hydrocarbon (PAH) content, and 2 gas-to-liquid (GTL) products, without any PAHs but otherwise similar properties to PS. The results showed that all PS extracts induced concentration-dependent in vitro PDT, as quantified in the ZET and that this potency is associated with their 3-5 ring PAH content...
December 7, 2018: ALTEX
Melissa Van Bossuyt, Els Van Hoeck, Tamara Vanhaecke, Vera Rogiers, Birgit Mertens
Due to the exponentially growing number of substances requiring safety evaluation, efficient prioritisation strategies are needed to identify those of highest concern. To limit unnecessary animal testing, such strategies should respect the 3R principles (Replacement, Reduction, Refinement). In the present study, a strategy based on non-animal approaches was developed to prioritize non-evaluated printed paper and board food contact material (FCM) substances for further in-depth safety evaluation. Within the strategy, focus was put on genotoxicity, a key toxicological endpoint when evaluating safety...
November 28, 2018: ALTEX
Stefanie Hofer, Marlies Stonig, Verena Wally, Anja Hartmann, Dietmar Fuchs, Martin Hermann, Martin Paparella, Markus Ganzera, Johanna M Gostner
Chemical UV-filters are frequently applied as active ingredients in sunscreen to protect from detrimental effects of UV radiation. Regardless, many of these compounds are not well characterized concerning their capacity to counteract UV induced reactive oxygen species (ROS). Intracellular ROS release is an early event upon UV exposure and a crucial trigger of reaction cascades that may provoke adverse effects both in short- and long-term. We report a strategy to assess the capacity of UV-filters (ecamsule, oxybenzone and menthyl anthranilate) to counteract UVA/UVB stress in the human keratinocyte HaCaT and the wildtype Fibs E6/E7 fibroblast cell lines...
November 27, 2018: ALTEX
Jaffar Kisitu, Susanne Hougaard Bennekou, Marcel Leist
Some laboratory issues are taken for granted as they seem to be simple and not worth much thought. This applies to "concentrations of a chemical tested for bioactivity/toxicity". Can there be any issue about weighing a compound, diluting it in culture medium and calculating the final mass (or particle number)-to-volume ratio? We discuss here some basic concepts about concentrations and their units, addressing also differences between "dose" and "concentration". The problem of calculated nominal concentrations not necessarily corresponding to local concentrations (relevant for biological effects of a chemical) is highlighted...
2019: ALTEX
Katarzyna S Kopanska, Markus Rimann, Sandra Latenser, Michael Raghunath
No abstract text is available yet for this article.
2019: ALTEX
Florenza Lüder Ripoli, Manuela Buettner, André Bleich
No abstract text is available yet for this article.
2019: ALTEX
Corina Gericke, Silke Strittmatter
No abstract text is available yet for this article.
2019: ALTEX
Thomas Hartung, Rob De Vries, Sebastian Hoffmann, Helena T Hogberg, Lena Smirnova, Katya Tsaioun, Paul Whaley, Marcel Leist
A good experiment reported badly is worthless. Meaningful contributions to the body of science are made by sharing the full methodology and results so that they can be evaluated and reproduced by peers. Erroneous and incomplete reporting does not do justice to the resources spent on conducting the experiment and the time peers spend reading the article. In theory peer-review should ensure adequate reporting - in practice it does not. Many areas have developed reporting standards and checklists to support the adequate reporting of scientific efforts, but in vitro research still has no generally accepted criteria...
2019: ALTEX
Eva Petrovova, Maria Giretova, Alena Kvasilova, Oldrich Benada, Jan Danko, Lubomir Medvecky, David Sedmera
Using scaffolds with appropriate porosity represents a potential approach for repair of critical-size bone defects. Vascularization is essential for bone formation and healing. This study investigates methods for monitoring angiogenesis within porous biopolymer scaffolds on the basis of polyhydroxybutyrate (PHB)/chitosan. We use the chick and quail chorioallantoic membrane (CAM) assay as an in vivo model focused on the formation of new blood vessels inside the implant structure. Chemical properties of the surface in biopolymer scaffold matrix were characterized as well as the tissue reaction of the CAM...
November 23, 2018: ALTEX
Marcia Bodero, Toine F H Bovee, Liza Portier, Peter J M Hendriksen
The mouse bioassay for the detection of marine biotoxins in shellfish products is 40 years old and still in use. A full ban or total replacement of this in vivo test has been postponed because of the fear that current chemical-based detection methods could miss a new emerging toxin. In order to fully replace the mouse bioassay, more efforts are needed on the search for functional assays with specific endpoints. Gene expression elicited by diarrheic shellfish poisons in Caco-2 cells allowed us to determine three 'DSP profiles', i...
November 21, 2018: ALTEX
Fei-Ya Luo, Zhe Su, Jing Wu, Feng-Lan Zhang, Shu-Xia Xing, Gang-Li Wang, Yong Lu
No abstract text is available yet for this article.
November 19, 2018: ALTEX
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