ALTEXPub Date : 2019-01-01DOI: 10.14573/altex.1812191
Thomas Hartung, Rob De Vries, Sebastian Hoffmann, Helena T Hogberg, Lena Smirnova, Katya Tsaioun, Paul Whaley, Marcel Leist
{"title":"Toward Good In Vitro Reporting Standards.","authors":"Thomas Hartung, Rob De Vries, Sebastian Hoffmann, Helena T Hogberg, Lena Smirnova, Katya Tsaioun, Paul Whaley, Marcel Leist","doi":"10.14573/altex.1812191","DOIUrl":"https://doi.org/10.14573/altex.1812191","url":null,"abstract":"<p><p>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. It is characterized by a \"Wild West\" or \"anything goes\" attitude. Such a culture may undermine trust in the reproducibility of animal-free methods, and thus parallel the \"reproducibility crisis\" discussed for other life science fields. The increasing data retrieval needs of computational approaches (in extreme as \"big data\" and artificial intelligence) makes reporting quality even more important so that the scientific community can take full advantage of the results. The first priority of reporting standards is to ensure the completeness and transparency of information provided (data focus). The second tier is a quality of data display that makes information digestible and easy to grasp, compare and further analyze (information focus). This article summarizes a series of initiatives geared towards improving the quality of in vitro work and its reporting. This shall ultimately lead to Good In Vitro Reporting Standards (GIVReSt).</p>","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"3-17"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36898820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2019-01-01Epub Date: 2018-11-19DOI: 10.14573/altex.1808021
Fei-Ya Luo, Zhe Su, Jing Wu, Feng-Lan Zhang, Shu-Xia Xing, Gang-Li Wang, Yong Lu
{"title":"The current status of alternative methods for cosmetics safety assessment in China.","authors":"Fei-Ya Luo, Zhe Su, Jing Wu, Feng-Lan Zhang, Shu-Xia Xing, Gang-Li Wang, Yong Lu","doi":"10.14573/altex.1808021","DOIUrl":"https://doi.org/10.14573/altex.1808021","url":null,"abstract":"","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"136-139"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36688996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2019-01-01Epub Date: 2019-06-03DOI: 10.14573/altex.1812173
Stefania Serra, Monica Vaccari, Maria Grazia Mascolo, Francesca Rotondo, Cristina Zanzi, Laura Polacchini, Christine Behle Wagner, Thorsten Kunkelmann, Sabine Perschbacher, Albrecht Poth, Sandro Grilli, Miriam N Jacobs, Annamaria Colacci
{"title":"Hazard assessment of air pollutants: The transforming ability of complex pollutant mixtures in the Bhas 42 cell model.","authors":"Stefania Serra, Monica Vaccari, Maria Grazia Mascolo, Francesca Rotondo, Cristina Zanzi, Laura Polacchini, Christine Behle Wagner, Thorsten Kunkelmann, Sabine Perschbacher, Albrecht Poth, Sandro Grilli, Miriam N Jacobs, Annamaria Colacci","doi":"10.14573/altex.1812173","DOIUrl":"https://doi.org/10.14573/altex.1812173","url":null,"abstract":"<p><p>The use of in vitro alternative methods is a promising approach to characterize the hazardous properties of environmental chemical mixtures, including urban airborne particulate matter (PM). The aim of this study was to examine seasonal differences in the toxic and transforming potential of PM samples, by using the in vitro cell transformation assay in Bhas 42 cells for the prediction of potential carcinogenic effects. Bhas 42 cells are already initiated, and the v-Ha-ras transfection, together with genetic modification following the immortalization process, makes them a valuable model to study the late steps of cellular transformation leading to the acquisition of the malignant phenotype. Exposure to organic extracts of PM1 and PM2.5 induced dose-related effects. The transforming and cytotoxic properties are related to the amount of PM collected during the sampling campaign and associated with the concentrations of polycyclic aromatic hydrocarbons (PAHs) in the samples. All the samples induced cell transformation following prolonged exposure of 2 weeks. Our results support the utility of the in vitro top-down approach to characterise the toxicity of real mixtures, thereby supporting regulators in the decision-making process. The results also identify the need for appropriate assay selection within the in vitro testing strategy to address the complexity of the final adverse outcomes.</p>","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"623-633"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37343249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2019-01-01Epub Date: 2018-10-16DOI: 10.14573/altex.1808241
Edward J Perkins, Kalyan Gayen, Jason E Shoemaker, Philipp Antczak, Lyle Burgoon, Francesco Falciani, Steve Gutsell, Geoff Hodges, Aude Kienzler, Dries Knapen, Mary McBride, Catherine Willett, Francis J Doyle, Natàlia Garcia-Reyero
{"title":"Chemical hazard prediction and hypothesis testing using quantitative adverse outcome pathways.","authors":"Edward J Perkins, Kalyan Gayen, Jason E Shoemaker, Philipp Antczak, Lyle Burgoon, Francesco Falciani, Steve Gutsell, Geoff Hodges, Aude Kienzler, Dries Knapen, Mary McBride, Catherine Willett, Francis J Doyle, Natàlia Garcia-Reyero","doi":"10.14573/altex.1808241","DOIUrl":"https://doi.org/10.14573/altex.1808241","url":null,"abstract":"<p><p>Current efforts in chemical safety are focused on utilizing human in vitro or alternative animal data in biological pathway context. However, it remains unclear how biological pathways, and toxicology data developed in that context, can be used to quantitatively facilitate decision-making. The objective of this work is to determine if hypothesis testing using Adverse Outcome Pathways (AOPs) can provide quantitative chemical hazard predictions. Current methods for predicting hazards of chemicals in a biological pathway context were extensively reviewed, specific case studies examined and computational modeling used to demonstrate quantitative hazard prediction based on an AOP. Since AOPs are chemically agnostic, we propose that AOPs function as hypotheses for how specific chemicals may cause adverse effects via specific pathways. Three broad approaches were identified for testing the hypothesis with AOPs, semi-quantitative weight of evidence, probabilistic, and mechanistic modeling. We then demonstrate how these approaches could be used to test hypotheses using high throughput in vitro data and alternative animal data. Finally, we discuss standards in development and documentation that would facilitate use in a regulatory context. We conclude that quantitative AOPs provide a flexible hypothesis framework for predicting chemical hazards. It accommodates a wide range of approaches that are useful at many stages and build upon one another to become increasingly quantitative.</p>","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"91-102"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36583273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2019-01-01Epub Date: 2018-08-03DOI: 10.14573/altex.1805131
Wen Y Chung, Joseph J Wanford, Rohan Kumar, John D Isherwood, Richard D Haigh, Marco R Oggioni, Ashley R Dennison, Giuseppe Ercoli
{"title":"An ex vivo porcine spleen perfusion as a model of bacterial sepsis.","authors":"Wen Y Chung, Joseph J Wanford, Rohan Kumar, John D Isherwood, Richard D Haigh, Marco R Oggioni, Ashley R Dennison, Giuseppe Ercoli","doi":"10.14573/altex.1805131","DOIUrl":"https://doi.org/10.14573/altex.1805131","url":null,"abstract":"An ex vivo, porcine spleen perfusion model was established to study the early events occurring in the spleen prior to the onset of bacterial sepsis, using organs retrieved from animals slaughtered for food production. Porcine spleens were harvested from adult pigs and connected to a normothermic extracorporeal perfusion circuit. A constant perfusion of heparinized blood was performed for 6 hours. After injection of Streptococcus pneumoniae to the circuit serial samples of both blood and spleen biopsies were collected and analysed. Functionality of the perfused organs was assessed by monitoring the blood-gas parameters, flow rate and filtering capability of the organ. Interestingly, we observed full clearance of bacteria from the blood and an increase in bacterial counts in the spleen. Classical histology and immunohistochemistry on biopsies also confirmed no major damages in the organ architecture and changes in the immune cell distribution, other than the presence of clusters of pneumococci. A time-course study confirmed that each focus of infection derived from the replication of single pneumococcal cells within splenic macrophages. The model proposed - in line with the 3Rs principles - has utility in the replacement of experimental animals in infection research. Murine models are prevalently used to study pneumococcal infections, but are often not predictive for humans due to substantial differences in the immune systems of the two species. This model is designed to overcome these limitations, since porcine immunology and splenic architecture in particular, closely resemble those of humans.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"29-38"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36371476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2019-01-01Epub Date: 2019-03-29DOI: 10.14573/altex.1811061
Kris A Descovich, Susan E Richmond, Matthew C Leach, Hannah M Buchanan-Smith, Paul Flecknell, David A H Farningham, Claire Witham, M Carolyn Gates, Sarah-Jane Vick
{"title":"Opportunities for refinement in neuroscience: Indicators of wellness and post-operative pain in laboratory macaques.","authors":"Kris A Descovich, Susan E Richmond, Matthew C Leach, Hannah M Buchanan-Smith, Paul Flecknell, David A H Farningham, Claire Witham, M Carolyn Gates, Sarah-Jane Vick","doi":"10.14573/altex.1811061","DOIUrl":"10.14573/altex.1811061","url":null,"abstract":"<p><p>Being able to assess pain in nonhuman primates undergoing biomedical procedures is important for preventing and alleviating pain, and for developing better guidelines to minimise the impacts of research on welfare in line with the 3Rs principle of Refinement. Nonhuman primates are routinely used biomedical models however it remains challenging to recognise negative states, including pain, in these animals. This study aimed to identify behavioural and facial changes that could be used as pain or general wellness indicators in the rhesus macaque (Macaca mulatta). Thirty-six macaques scheduled for planned neuroscience procedures were opportunistically monitored at four times: Pre-Operative (PreOp), Post-Operative (PostOp) once the effects of anaesthesia had dissipated, Pre-Analgesia (PreAn) on the subsequent morning prior to repeating routine analgesic treatment, and Post-Analgesia (PostAn) following administration of analgesia. Pain states were expected to be absent in PreOp, moderate in PreAn, and mild or absent in PostOp and PostAn when analgesia had been administered. Three potential pain indicators were identified: lip tightening and chewing, which were most likely to occur in PreAn, and running which was least likely in PreAn. Arboreal behaviour indicated general wellness, while half-closed eyes, leaning of the head or body shaking indicated the opposite. Despite considerable individual variation, behaviour and facial expressions could offer important indicators of pain and wellness and should be routinely quantified, and appropriate interventions applied to prevent or alleviate pain, and promote positive welfare.</p>","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"535-554"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37263906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2018-01-01DOI: 10.14573/altex.1803201
Arti Ahluwalia, Anna Maria Bassi, Paolo Milazzo
{"title":"Inauguration of the Centro 3R for the promotion of 3Rs principles in teaching and research.","authors":"Arti Ahluwalia, Anna Maria Bassi, Paolo Milazzo","doi":"10.14573/altex.1803201","DOIUrl":"https://doi.org/10.14573/altex.1803201","url":null,"abstract":"","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"260-261"},"PeriodicalIF":5.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36027728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2018-01-01Epub Date: 2017-09-18DOI: 10.14573/altex.1707171
Serena Manganelli, Benoît Schilter, Emilio Benfenati, Alberto Manganaro, Elena Lo Piparo
{"title":"Integrated strategy for mutagenicity prediction applied to food contact chemicals.","authors":"Serena Manganelli, Benoît Schilter, Emilio Benfenati, Alberto Manganaro, Elena Lo Piparo","doi":"10.14573/altex.1707171","DOIUrl":"https://doi.org/10.14573/altex.1707171","url":null,"abstract":"<p><p>Food contamination due to unintentional leakage of chemicals from food contact materials (FCM) is a source of increasing concern. Since for many of these substances, only limited or no toxicological data are available, the development of alternative methodologies to establish rapidly and cost-efficiently level of safety concern is critical to ensure adequate consumer protection. Computational toxicology methods are considered the most promising solutions to cope with this data gap. In particular, mutagenicity assessment has a particular relevance and is a mandatory requirement for all substances released from plastic FCM, regardless how low migration and exposure are. In the present work, a strategy integrating a number of (Quantitative) Structure Activity Relationship ((Q)SAR) models for Ames mutagenicity predictions is proposed. A list of chemicals representing likely migrating moieties from FCM was selected to test the value of the newly defined strategy and the possibility to combine predictions given by the different algorithms was evaluated. In particular, a scheme to integrate mutagenicity estimations into a single final assessment was developed resulting in an increased domain of applicability. In most cases, a deeper analysis of experimental data, where available, allowed fixing misclassification errors, highlighting the importance of data curation in the development, validation and application of in silico methods. The high accuracy of the strategy provided the rationales for its application for toxicologically uncharacterized chemicals. Finally, the overall strategy of integration will be automated through its implementation into a freely available software application.</p>","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"169-178"},"PeriodicalIF":5.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35523715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALTEXPub Date : 2018-01-01DOI: 10.14573/altex.1802122
Chiara Scanarotti, Costanza Rovida, Susanna Penco, Stefania Vernazza, Sara Tirendi, Ilaria Baldelli, Rosagemma Ciliberti, Anna Maria Bassi
{"title":"Giving meaning to alternative methods to animal testing.","authors":"Chiara Scanarotti, Costanza Rovida, Susanna Penco, Stefania Vernazza, Sara Tirendi, Ilaria Baldelli, Rosagemma Ciliberti, Anna Maria Bassi","doi":"10.14573/altex.1802122","DOIUrl":"https://doi.org/10.14573/altex.1802122","url":null,"abstract":"","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"256-257"},"PeriodicalIF":5.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36027730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}