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- In Silico Prediction of Eye Irritation Using Hansen Solubility Parameters
and Predicted pKa Values-
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Authors: Martin Andersson, Ulf Norinder, Swapnil Chavan, Ian Cotgreave Abstract: Alternatives to Laboratory Animals, Ahead of Print. An in silico method has been developed that permits the binary differentiation between pure liquids causing serious eye damage or eye irritation, and pure liquids with no need for such classification, according to the UN GHS system. The method is based on the finding that the Hansen Solubility Parameters (HSP) of a liquid are collectively important predictors for eye irritation. Thus, by applying a two-tier approach in which in silico predicted pKa values (firstly) and a trained model based solely on in silico-predicted HSP data (secondly) were used, we have developed, and validated, a fully in silico approach for predicting the outcome of a Draize test (in terms of UN GHS Cat. 1/Cat. 2A/Cat. 2B or UN GHS No Cat.) with high validation set performance (sensitivity = 0.846, specificity = 0.818, balanced accuracy = 0.832) using SMILES only. The method is applicable to pure non-ionic liquids with molecular weight below 500 g/mol, fewer than six hydrogen bond donors (e.g. nitrogen–hydrogen or oxygen–hydrogen bonds) and fewer than eleven hydrogen bond acceptors (e.g. nitrogen or oxygen atoms). Due to its fully in silico characteristics, this method can be applied to pure liquids that are still at the desktop design stage and not yet in production. Citation: Alternatives to Laboratory Animals PubDate: 2023-05-15T01:20:02Z DOI: 10.1177/02611929231175676
- Editorial
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-05-13T08:59:00Z DOI: 10.1177/02611929231175315
- Use of the Allium cepa Model to Assess the Cytogenotoxicity of Luffariella
herdmani Marine Sponge Extract-
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Authors: Sashini U. Kuruppuarachchi, Uthpala A. Jayawardena, Varuni K. Gunathilake Abstract: Alternatives to Laboratory Animals, Ahead of Print. Marine sponge extracts are known to contain potentially toxic compounds that have biological activities of possible pharmacological interest. Thus, it is vital that biological models are used for the preliminary toxicity screening of such extracts. The present study reports the use of Allium cepa, a low-cost plant-based in vivo model, to assess the cytotoxicity and genotoxicity of Luffariella herdmani marine sponge crude extract (SCE). Pre-germinated onion bulbs, exposed for 96 hours to different concentrations of SCE (ranging from 0.3125 to 20 μg/ml), were used to determine general cytotoxicity. Root length as well as morphological abnormalities were recorded. Genotoxicity was assessed by exposing the root tips to SCE (0.3125–20 μg/ml) and the appropriate controls for 48 hours, and then staining with acetocarmine. The Mitotic Index (MI), Mitotic Phase Indices (MPIs) and chromosomal aberrations were evaluated and recorded. SCE inhibited A. cepa root growth (EC50 = 10.34 μg/ml) and elicited a mitodepressive effect (LC50 = 1.95 μg/ml) in a dose-dependent and significant manner. In addition, macroscopic alterations as well as chromosomal aberrations were detected. Overall, our findings indicate that L. herdmani crude extract exhibits cytotoxic and genotoxic activity, suggesting that it might contain substances with anti-proliferative/anticancer potential that could be subject to further characterisation. Citation: Alternatives to Laboratory Animals PubDate: 2023-04-26T12:22:17Z DOI: 10.1177/02611929231171943
- A Human Cell-based Assay to Assess the Induction of Vasculature Formation
for Non-genotoxic Carcinogenicity Testing Purposes: A Pilot Study-
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Authors: Veera Hautanen, Tarja Toimela, Martin Paparella, Tuula Heinonen Abstract: Alternatives to Laboratory Animals, Ahead of Print. The induction of vasculature formation is proposed to be a significant mechanism behind the non-genotoxic carcinogenicity of a chemical. The vasculature formation model used in this study is based on the coculture of human primary HUVECs and hASCs. This model was used to develop an assay to assess the induction of vasculature formation. Three assay protocols, based on different conditions, were developed and compared in order to identify the optimal conditions required. Some serum supplements and growth factors were observed to be essential for initiating vasculature formation. Of the studied putative positive reference chemicals, aspartame, sodium nitrite, bisphenol A and nicotine treatment led to a clear induction of vasculature formation, but arsenic and cadmium treatment only led to a slight increase. This human cell-based assay has the potential to be used as one test within a next generation testing battery, to assess the non-genotoxic carcinogenicity of a chemical through the mechanism of vasculature formation induction. Citation: Alternatives to Laboratory Animals PubDate: 2023-04-26T07:44:55Z DOI: 10.1177/02611929231171165
- Resources Round-up
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-04-19T10:57:49Z DOI: 10.1177/02611929231170667
- Conference Diary
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-04-17T05:24:40Z DOI: 10.1177/02611929231170669
- Spotlight on Three Rs Progress
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-04-17T05:09:00Z DOI: 10.1177/02611929231170668
- The Application of New Approach Methodologies in Respiratory Disease
Research: Their Role in Improving Translational Medicine from Bench to Bedside-
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Authors: Artur C.G. da Silva, Marize C. Valadares Abstract: Alternatives to Laboratory Animals, Ahead of Print. The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials. Citation: Alternatives to Laboratory Animals PubDate: 2023-04-17T02:13:22Z DOI: 10.1177/02611929231170392
- Thanks to Reviewers
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-02-02T03:12:50Z DOI: 10.1177/02611929231154972
- Editorial
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Authors: Judith C. Madden First page: 83 Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-02-17T06:07:56Z DOI: 10.1177/02611929231157832
- Spotlight on Three Rs Progress
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First page: 85 Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-02-07T12:45:11Z DOI: 10.1177/02611929231157876
- Resources Round-up
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First page: 88 Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-02-11T02:17:12Z DOI: 10.1177/02611929231157875
- The 19th FRAME Annual Lecture, November 2022: Safer Chemicals and
Sustainable Innovation Will Be Achieved by Regulatory Use of Modern Safety Science, Not by More Animal Testing-
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Authors: Julia H. Fentem First page: 90 Abstract: Alternatives to Laboratory Animals, Ahead of Print. The decisions we make on chemical safety, for consumers, workers and the environment, must be based on the best scientific data and knowledge available. Rapid advances in biology, in cell-based technologies and assays, and in analytical and computational approaches, have led to new types of highly relevant scientific data being generated. Such data enable us to improve the safety decisions we make, whilst also enabling us to avoid animal testing. Stimulated by the UK and EU bans on animal testing for cosmetics, Next Generation Risk Assessment (NGRA) approaches, which integrate various types of non-animal scientific data, have been established for assessing the safety of chemical ingredients used in cosmetics and other consumer products. In stark contrast, the chemicals regulations in Europe and other parts of the world have not kept pace with modern safety science and regulators are now mandating even more animal testing. Urgently closing this science–regulation gap is essential to upholding the EU’s legislative requirement that any animal testing is a last resort. The ongoing revisions of UK and EU chemicals strategy and regulations provide an opportunity to fundamentally change the design and assessment paradigm needed to underpin safe and more sustainable innovation, through applying the best science and tools available rather than continuing to be anchored in animal tests dating back many decades. A range of initiatives have recently been launched in response to this urgent need, in the UK as well as in the EU. Citation: Alternatives to Laboratory Animals PubDate: 2023-03-01T09:46:24Z DOI: 10.1177/02611929231158236
- Poor Translatability of Biomedical Research Using Animals — A
Narrative Review-
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Authors: Lindsay J. Marshall, Jarrod Bailey, Manuela Cassotta, Kathrin Herrmann, Francesca Pistollato First page: 102 Abstract: Alternatives to Laboratory Animals, Ahead of Print. The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this. Citation: Alternatives to Laboratory Animals PubDate: 2023-03-08T07:42:46Z DOI: 10.1177/02611929231157756
- In Vitro Dengue Virus Inhibition by Aqueous Extracts of Aegle marmelos,
Munronia pinnata and Psidium guajava-
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Authors: Kalani Gayathri Jayasekara, Preethi Soysa, Thusharie Sugandhika Suresh, Charitha Lakshini Goonasekara, Kamani Mangalika Gunasekera First page: 136 Abstract: Alternatives to Laboratory Animals, Ahead of Print. Dengue is an arboviral (insect-transmitted) infection of global concern. Currently, there are still no specific dengue antiviral agents to treat the disease. Plant extracts have been used in traditional medicine for treating various viral infections — thus, in the present study, aqueous extracts of dried flowers of Aegle marmelos (AM), whole plant of Munronia pinnata (MP) and leaves of Psidium guajava (PG) were investigated for their potential capacity to inhibit dengue virus infection of Vero cells. The maximum non-toxic dose (MNTD) and the 50% cytotoxic concentration (CC50) were determined by using the MTT assay. A plaque reduction antiviral assay was carried out with dengue virus types 1 (DV1), 2 (DV2), 3 (DV3) and 4 (DV4), in order to calculate the half-maximum inhibitory concentration (IC50). AM extract inhibited all four virus serotypes tested; MP extract inhibited DV1, DV2 and DV4, but not DV3; PG extract inhibited DV1, DV2 and DV4, but not DV3. Thus, the results suggest that AM is a promising candidate for the pan-serotype inhibition of dengue viral activity. Citation: Alternatives to Laboratory Animals PubDate: 2023-02-16T05:40:44Z DOI: 10.1177/02611929231158243
- A Short History of the Consideration of Sex Differences in Biomedical
Research — Lessons for the In Vitro Community from Animal Models and Human Clinical Trials-
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Authors: Helena Niobe Renate Gutleb, Arno Christian Gutleb First page: 144 Abstract: Alternatives to Laboratory Animals, Ahead of Print. In recent decades, it has become clear that in many fields — such as drug development, particularly with regard to drug dosage and specific disease treatment — the sex of a patient must be taken into consideration, in view of the fact that male and female physiology and pathophysiology show many differences of practical concern. While, in the last decade or so, considerable efforts have been undertaken to consider the sex of the animals during the planning of experiments, this topic has just started to be acknowledged in in vitro studies. Cells in such studies seem mainly to be used according to their availability, without considering the sex of the original donor. Even when such information is available, experimental data are reported without overtly detailing this information. In recent years, the increasing complexity of in vitro models (e.g. stem cell-based, 3-D cultures, organoids, or organ-on-a-chip technologies) has contributed to systems that better resemble the human in vivo situation. However, the issue of the sex of the experimental organisms being used has not yet been properly taken up by the cell culture community. Thus, alongside the increasing complexity of multicell-type models, we now see in vitro models that incorporate cells from both male and female origin — this representing, in fact, a genetic chimaera. Here, we aim to discuss where we are currently, with respect to considering the sex of any animals or humans used in experiments, and we try to identify what is lacking in the cell culture field, in order to help facilitate change. Citation: Alternatives to Laboratory Animals PubDate: 2023-02-08T06:26:23Z DOI: 10.1177/02611929231156720
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First page: 151 Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2023-02-07T12:50:05Z DOI: 10.1177/02611929231157877
- Corrigendum to Case Studies Exemplifying the Transition to Animal
Component-Free Cell Culture-
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2022-12-01T11:00:56Z DOI: 10.1177/02611929221141160
- Corrigendum to The Relevance of In Silico, In Vitro and Non-human Primate
Based Approaches to Clinical Research on Major Depressive Disorder-
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2020-09-24T12:17:20Z DOI: 10.1177/0261192920964278
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