Altex-Alternatives To Animal Experimentation最新文献

{"title":"A systematic analysis of read-across adaptations in testing proposal evaluations by the European Chemicals Agency.","authors":"Hannah M Roe, Han-Hsaun D Tsai, Nicholas Ball, Fred A Wright, Weihsueh A Chiu, Ivan Rusyn","doi":"10.14573/altex.2408292","DOIUrl":"10.14573/altex.2408292","url":null,"abstract":"<p><p>An essential aspect of the EU’s Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation is the European Chemicals Agency’s (ECHA) evaluation of testing proposals submitted by registrants to address data gaps. Registrants may propose adaptations, such as read-across, to waive standard testing; however, it is widely believed that ECHA often finds justifications for read-across hypotheses inadequate. From 2008 to August 2023, 2,630 testing proposals were submitted to ECHA; of these, 1,538 had published decisions that were systematically evaluated in this study. Each document was manually reviewed and information extracted for further analyses, focusing on 17 assessment elements (AEs) from the Read-Across Assessment Framework (RAAF) and testing proposal evaluations (TPE). Each submission was classified as to the AEs relied upon by the registrants and by ECHA. Data was analyzed for patterns and associations. Adaptations were included in 23% (350) of proposals, with analogue (168) and group (136) read-across being most common. Of the 304 read-across hypotheses, 49% were accepted, with group read-across showing significantly higher odds of acceptance. Data analysis examined factors such as tonnage band (Annex), test guidelines, hypothesis AEs, and structural similarities of target and source sub­stances. While decisions were often context-specific, several significant associations influencing acceptance emerged. Overall, this analysis provides a comprehensive overview of 15 years of experience with testing proposal-specific read-across adaptations by both registrants and ECHA. These data will inform future submissions as they identify most critical AEs to increase the odds of read-across acceptance.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"22-38"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Software tools for systematic review literature screening and data extraction: Qualitative user experiences from succinct formal tests.","authors":"Cathalijn H C Leenaars, Frans Stafleu, André Bleich","doi":"10.14573/altex.2409251","DOIUrl":"10.14573/altex.2409251","url":null,"abstract":"<p><p>Systematic reviews (SRs) contribute to implementing the 3Rs in preclinical research. With the ever-increasing amount of scientific literature, SRs require increasing time investment. Thus, using the most efficient review tools is essential. Most available software tools aid the screening process; tools for data extraction and/or multiple review phases are relatively scarce. Using a single platform for all review phases allows auto-transfer of references from one phase to the next and enables work on multiple phases at the same time. We performed succinct formal tests of four multiphase review tools that are free or relatively affordable: Covidence, Eppi, SRDR+ and SYRF. Our tests comprised full-text screening, sham data extraction, and discrepancy resolution in the context of parts of a systematic review. Screening was performed as per protocol. Sham data extraction comprised free text, numerical and categorial data. Both reviewers logged their experiences with the platforms throughout. These logs were qualitatively summarized and supplemented with further user experi­ences. We show value of all tested tools in the SR process. Which tool is optimal depends on multiple factors, comprising previous experience with the tool but also review type, review questions, and review team member enthusiasm.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"159-166"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human relevant frontiers in drug safety and efficacy.","authors":"Kasturi Mahadik, Annam Visala, Nabendu Chatterjee, Monika Pahuja, Viraj Mehta, Tejaswini Dhurde, Goutami Nayak, Tausif Ahmed, Nirnith Devireddy, Anita Krishnan, Kasinath Viswanathan, Sonia Gandhi, Gaurav Mehta, Pranav Karmwar, Bhairav Paleja, Sujata Mohanty, Surat Parvatam, Ramjee Pallela, Madhusudhana Rao","doi":"10.14573/altex.2411131","DOIUrl":"https://doi.org/10.14573/altex.2411131","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"42 1","pages":"146-151"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long way from raw data to NAM-based information: Overview on data layers and processing steps.","authors":"Jonathan Blum, Markus Brüll, Jan G Hengstler, Daniel R Dietrich, Andreas J Gruber, Michele Dipalo, Udo Kraushaar, Iris Mangas, Andrea Terron, Ellen Fritsche, Philip Marx-Stoelting, Barry Hardy, Andreas Schepky, Sylvia Escher, Thomas Hartung, Robert Landsiedel, Alex Odermatt, Magdalini Sachana, Katharina Koch, Arif Dönmez, Stefan Masjosthusmann, Kathrin Bothe, Stefan Schildknecht, Mario Beilmann, Joost B Beltman, Suzanne Fitzpatrick, Aswin Mangerich, Markus Rehm, Silvia Tangianu, Franziska M Zickgraf, Hennicke Kamp, Gerhard Burger, Bob van de Water, Nicole Kleinstreuer, Andrew White, Marcel Leist","doi":"10.14573/altex.2412171","DOIUrl":"https://doi.org/10.14573/altex.2412171","url":null,"abstract":"<p><p>Toxicological test methods generate raw data and provide instructions on how to use these to determine a final outcome such as a classification of test compounds as hits or non-hits. The data processing pipeline provided in the test method description is often highly complex. Usually, multiple layers of data, ranging from a machine-generated output to the final hit definition, are considered. Transition between each of these layers often requires several data processing steps. As changes in any of these processing steps can impact the final output of new approach methods (NAMs), the processing pipeline is an essential part of a NAM description and should be included in reporting templates such as the ToxTemp. The same raw data, processed in different ways, may result in different final outcomes that may affect the readiness status and regulatory acceptance of the NAM, as an altered output can affect robustness, performance, and relevance. Data management, pro­cessing, and interpretation are therefore important elements of a comprehensive NAM definition. We aim to give an overview of the most important data levels to be considered during the devel­opment and application of a NAM. In addition, we illustrate data processing and evaluation steps between these data levels. As NAMs are increasingly standard components of the spectrum of toxi­cological test methods used for risk assessment, awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"42 1","pages":"167-180"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3Rs: Progress or a fig leaf? Animalfree Research Forum 2024.","authors":"Miriam A Zemanova, Silvia Frey","doi":"10.14573/altex.2411191","DOIUrl":"https://doi.org/10.14573/altex.2411191","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"42 1","pages":"145-146"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting acute oral toxicity using AcutoX: An animal product-free and metabolically relevant human cell-based test.","authors":"Thomas A Ward, Hannah Goldsby, Michael Connolly, Clive Roper, Carol Treasure","doi":"10.14573/altex.2311142","DOIUrl":"10.14573/altex.2311142","url":null,"abstract":"<p><p>AcutoX is a human in vitro test method for the evaluation of acute oral toxicity developed using a library of 67 curated test chemicals. These chemicals cover a wide variety of chemistries, indus­trial sectors, rodent toxicities, and all EPA and GHS hazard categories. The test uses two different cytotoxicity endpoints (neutral red uptake and MTT metabolism), performed both in the presence and absence of pooled human liver extract (S9), to produce four EC50 values. The EC50 values are used in prediction models to assign a “highly toxic” and “low toxicity” category for both EPA and GHS classification, which can be further refined to assign a hazard category. The binary “highly toxic” / “low toxicity” prediction model has an accuracy of 73.8% and 63.1% for EPA and GHS, respectively, with the subsequent hazard categorization offering a protective prediction (correct or higher category) in 90.0% and 93.3% of cases, respectively. Moreover, the AcutoX test can identify chemicals activated or detoxified by liver metabolism.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"39-55"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of the DASF compared to other combinations of OECD NAMs for eye hazard identification of surfactants.","authors":"Nathalie Alépée, Karsten R Mewes, Takayuki Abo, Alessandra Cavarzan, Chelsea O'Driscoll, Els Adriaens","doi":"10.14573/altex.2406031","DOIUrl":"10.14573/altex.2406031","url":null,"abstract":"<p><p>Currently, the OECD has adopted three defined approaches (DAs) for eye hazard identification of non-surfactant liquids and solids (TG 467) according to the three UN GHS categories. We are now expanding the applicability domain with a new DA for chemicals having surfactant properties (DASF). It is based on a combination of recombinant human cornea-like epithelium test methods (TG 492: EpiOcular™ EIT or SkinEthic™ HCE EIT) and a modification of the Short Time Exposure (TG 491) method. The aim of the current study was to compare the performance of the DASF with the performance of other NAMs currently included in the OECD TGs and with the classification based on the Draize eye test to identify potential additional DAs. The minimum performance criteria (75% Cat. 1, 50% Cat. 2, 70% No Cat.) used for the adoption of the DAs currently included in TG 467 were used for this purpose. The DASF identified 90.9% of Cat. 1 (N = 23), 77.8% of Cat. 2 (N = 9), and 76.0% of No Cat. (N = 17) surfactants, meeting the minimum performance criteria. Some of the NAMs that are currently included in the TGs seem promising methods to become part of a DA to identify Cat. 1 or No Cat. for eye hazard assessment of surfactants. However, the number of surfactants that have been tested to evaluate their reliability and relevance was often too low. To date, the DASF is the only DA that has evaluated a sufficiently large number of surfactants and whose performance meets the minimum performance criteria.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"75-90"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the C17.2 cell line as test system for endocrine disruption-induced developmental neurotoxicity.","authors":"Andrea Cediel-Ulloa, Roseline Awoga, Arif Dönmez, Ximiao Yu, Anda Gliga, Kristina Attoff, Anna Forsby, Joëlle Rüegg","doi":"10.14573/altex.2404131","DOIUrl":"10.14573/altex.2404131","url":null,"abstract":"<p><p>Hormone signaling plays an essential role during fetal life and is vital for brain development. Endo­crine-disrupting chemicals can interfere with the hormonal milieu during this critical time-period, disrupting key neurodevelopmental processes. Hence, there is a need for the development of assays that evaluate developmental neurotoxicity (DNT) induced by an endocrine mode of action. Herein, we evaluated the neural progenitor C17.2 cell line as an in vitro test system to aid in the detection of endocrine disruption-induced DNT. For this, C17.2 cells were exposed during 10 days of dif­ferentiation to agonists and antagonists of the thyroid hormone (THR), glucocorticoid (GR), retinoic acid (RAR), retinoic x (RXR), oxysterol (LXR), estrogen (ER), androgen (AR), and peroxisome prolif­erator activated delta (PPARβ/δ) receptors, as well as to the agonist of the vitamin D (VDR) receptor. Upon exposure and differentiation, neuronal morphology (neurite outgrowth and branching) and the percentage of neurons in culture were assessed by immunofluorescence. For this, the cells were stained for βIII-tubulin (neuronal marker). C17.2 cells decreased neurite outgrowth and branching in response to RAR, RXR and PPARβ/δ agonists. Exposure to the GR agonist increased the number of cells differentiating into neurons, while exposure to the RXR agonist had the opposite effect. With this approach, we demonstrate that C17.2 cells are responsive to GR, RAR, RXR, and PPARβ/δ agonists and hence could be useful to develop a test system for hazard assessment of endocrine disruption-induced DNT.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"91-110"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunities and challenges for human microphysiological systems in drug development.","authors":"Shekh M Rahman, Ashok Krishna, Catherine Sullenberger, Ye Eun Jeong, M Iveth Garcia, Bhavya Bhardwaj, Robert M Geiger, Ksenia Blinova, Kevin A Ford","doi":"10.14573/altex.2409221","DOIUrl":"https://doi.org/10.14573/altex.2409221","url":null,"abstract":"<p><p>Microphysiological systems (MPS) are complex in vitro tools that incorporate cells derived from various healthy or disease-state human or animal tissues and organs. While MPS have limitations, including a lack of globally harmonized guidelines for standardization, they have already proven impactful in certain areas of drug development. Further research and regulatory acceptance of MPS will contribute to making them even more effective tools in the future. This review explores the potential applications of human liver, gut, lung, and cardiac MPS in drug development, focusing on disease modeling, safety assessment, and pharmacokinetic studies. Various technical parameters and relevant endpoints for system assessment are discussed alongside challenges such as cell sourcing, reproducibility, and the integration of multiple tissues or organs. The importance of collaborative efforts between academia, industry, and regulatory agencies to develop standardized protocols and validation criteria is emphasized. With ongoing advancements and cooperative initiatives, MPS are poised to play a significant role in enhancing the predictivity and reliability of nonclinical testing, thereby transforming drug development and regulatory processes.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of rat and human in vitro assays for evaluation of thyroid toxicity.","authors":"Laure Asselin, Audrey Baze, Betty Ory, Lucille Wiss, Amélie Schäfer, Liliia Horbal, Larry Higgins, Lysiane Richert","doi":"10.14573/altex.2405072","DOIUrl":"https://doi.org/10.14573/altex.2405072","url":null,"abstract":"<p><p>The effects of ten test chemicals towards thyroid sodium-iodide symporter (NIS), thyroid peroxidase (TPO), and deiodinases (DIOs) type I, II, and III were evaluated in in vitro rat and human systems and compared. Test chemicals known to directly affect TH levels in vivo were confirmed to effectively inhibit at least one of the tested in vitro endpoints, without significant disparities between species, and the tested compounds known to not affect thyroid function, were found ineffective. Interestingly, Iodide Transport Blocker 5, a potent non-competitive iodine uptake inhibitor, exhibited effects beyond direct NIS inhibition, by impacting NIS function through ATP depletion, and also inhibited TPO and DIO1/2 enzymes, although to a lesser extent. Finally, while of the four hepatic inducers known to affect thyroid function indirectly in rats through increased TH metabolism in the liver, dexamethasone, phenobarbital and pregnenolone 16α-carbonitrile were found ineffective in the herein described inhibition tests, rifampicin decreased rat and human TPO activities, highlighting a potential direct effect on thyroid function. This study demonstrates the usefulness of data generated by the rat and human in vitro NIS, TPO and DIOs test systems described here to support risk-based decisions.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}