Martin Andersson, Ulf Norinder, Swapnil Chavan, Ian Cotgreave
{"title":"<i>In Silico</i> Prediction of Eye Irritation Using Hansen Solubility Parameters and Predicted pKa Values.","authors":"Martin Andersson, Ulf Norinder, Swapnil Chavan, Ian Cotgreave","doi":"10.1177/02611929231175676","DOIUrl":"https://doi.org/10.1177/02611929231175676","url":null,"abstract":"<p><p>An <i>in silico</i> 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 <i>in silico</i>-predicted pKa values (firstly) and a trained model based solely on <i>in silico</i>-predicted HSP data (secondly) were used, we have developed, and validated, a fully <i>in silico</i> 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 <i>in silico</i> characteristics, this method can be applied to pure liquids that are still at the desktop design stage and not yet in production.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"204-209"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9625352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Application of New Approach Methodologies in Respiratory Disease Research: Their Role in Improving Translational Medicine from Bench to Bedside.","authors":"Artur C G da Silva, Marize C Valadares","doi":"10.1177/02611929231170392","DOIUrl":"https://doi.org/10.1177/02611929231170392","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"161-174"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veera Hautanen, Tarja Toimela, Martin Paparella, Tuula Heinonen
{"title":"A Human Cell-based Assay to Assess the Induction of Vasculature Formation for Non-genotoxic Carcinogenicity Testing Purposes: A Pilot Study.","authors":"Veera Hautanen, Tarja Toimela, Martin Paparella, Tuula Heinonen","doi":"10.1177/02611929231171165","DOIUrl":"https://doi.org/10.1177/02611929231171165","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"188-203"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sashini U Kuruppuarachchi, Uthpala A Jayawardena, Varuni K Gunathilake
{"title":"Use of the <i>Allium cepa</i> Model to Assess the Cytogenotoxicity of <i>Luffariella herdmani</i> Marine Sponge Extract.","authors":"Sashini U Kuruppuarachchi, Uthpala A Jayawardena, Varuni K Gunathilake","doi":"10.1177/02611929231171943","DOIUrl":"https://doi.org/10.1177/02611929231171943","url":null,"abstract":"<p><p>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 <i>Allium cepa</i>, a low-cost plant-based <i>in vivo</i> model, to assess the cytotoxicity and genotoxicity of <i>Luffariella herdmani</i> 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 <i>A. cepa</i> root growth (EC<sub>50</sub> = 10.34 μg/ml) and elicited a mitodepressive effect (LC<sub>50</sub> = 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 <i>L. herdmani</i> 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.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"175-187"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>In Vitro</i> Dengue Virus Inhibition by Aqueous Extracts of <i>Aegle marmelos</i>, <i>Munronia pinnata</i> and <i>Psidium guajava</i>.","authors":"Kalani Gayathri Jayasekara, Preethi Soysa, Thusharie Sugandhika Suresh, Charitha Lakshini Goonasekara, Kamani Mangalika Gunasekera","doi":"10.1177/02611929231158243","DOIUrl":"https://doi.org/10.1177/02611929231158243","url":null,"abstract":"<p><p>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 <i>Aegle marmelos</i> (AM), whole plant of <i>Munronia pinnata</i> (MP) and leaves of <i>Psidium guajava</i> (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 (CC<sub>50</sub>) 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 (IC<sub>50</sub>). 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.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 2","pages":"136-143"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"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.","authors":"Julia H Fentem","doi":"10.1177/02611929231158236","DOIUrl":"10.1177/02611929231158236","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 2","pages":"90-101"},"PeriodicalIF":2.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9203622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Poor Translatability of Biomedical Research Using Animals - A Narrative Review.","authors":"Lindsay J Marshall, Jarrod Bailey, Manuela Cassotta, Kathrin Herrmann, Francesca Pistollato","doi":"10.1177/02611929231157756","DOIUrl":"https://doi.org/10.1177/02611929231157756","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 2","pages":"102-135"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9556050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}