Applied In Vitro Toxicology最新文献

{"title":"Effect of African Potato (Hypoxis hemerocallidea) Extract and Its Constituents on PXR and CYP450 Enzymes","authors":"H. HaronMona, R. DaleOlivia, ZulfiqarFazila, W. Hong, G. ChittiboyinaAmar, A. KhanIkhlas, I. KhanShabana","doi":"10.1089/AIVT.2018.0022","DOIUrl":"https://doi.org/10.1089/AIVT.2018.0022","url":null,"abstract":"Abstract Introduction: Herb–drug interaction is an important clinical risk associated with the concomitant consumption of herbal supplements with conventional drugs. African potato (AP) (Hypoxis he...","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/AIVT.2018.0022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60778649","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}

{"title":"The Botanical Safety Consortium","authors":"RoeAmy L. Moderator, DeverJoseph T. Participants, GafnerStefan, S. MarsmanDaniel, V. RiderCynthia, SwiftSibyl","doi":"10.1089/AIVT.2018.29018.RTL","DOIUrl":"https://doi.org/10.1089/AIVT.2018.29018.RTL","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/AIVT.2018.29018.RTL","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42926123","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}

{"title":"Using Tox21 High-Throughput Screening Assays for the Evaluation of Botanical and Dietary Supplements.","authors":"Troy D Hubbard, Jui-Hua Hsieh, Cynthia V Rider, Nisha S Sipes, Alexander Sedykh, Bradley J Collins, Scott S Auerbach, Menghang Xia, Ruili Huang, Nigel J Walker, Michael J DeVito","doi":"10.1089/aivt.2018.0020","DOIUrl":"10.1089/aivt.2018.0020","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Recent nationwide surveys found that natural products, including botanical dietary supplements, are used by ∼18% of adults. In many cases, there is a paucity of toxicological data available for these substances to allow for confident evaluations of product safety. The National Toxicology Program (NTP) has received numerous nominations from the public and federal agencies to study the toxicological effects of botanical dietary supplements. The NTP sought to evaluate the utility of <i>in vitro</i> quantitative high-throughput screening (qHTS) assays for toxicological assessment of botanical and dietary supplements. <b><i>Materials and Methods:</i></b> In brief, concentration-response assessments of 90 test substances, including 13 distinct botanical species, and individual purported active constituents were evaluated using a subset of the Tox21 qHTS testing panel. The screen included 20 different endpoints that covered a broad range of biologically relevant signaling pathways to detect test article effects upon endocrine activity, nuclear receptor signaling, stress response signaling, genotoxicity, and cell death signaling. <b><i>Results and Discussion:</i></b> Botanical dietary supplement extracts induced measurable and diverse activity. Elevated biological activity profiles were observed following treatments with individual chemical constituents relative to their associated botanical extract. The overall distribution of activity was comparable to activities exhibited by compounds present in the Tox21 10K chemical library. <b><i>Conclusion:</i></b> Botanical supplements did not exhibit minimal or idiosyncratic activities that would preclude the use of qHTS platforms as a feasible method to screen this class of compounds. However, there are still many considerations and further development required when attempting to use <i>in vitro</i> qHTS methods to characterize the safety profile of botanical/dietary supplements.</p>","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"5 1","pages":"10-25"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37119793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An <i>In Vitro</i> Versus <i>In Vivo</i> Toxicogenomic Investigation of Prenatal Exposures to Tobacco Smoke.","authors":"Iain A Perry,&nbsp;Keith J Sexton,&nbsp;Zoë C Prytherch,&nbsp;Jason L Blum,&nbsp;Judith T Zelikoff,&nbsp;Kelly A BéruBé","doi":"10.1089/aivt.2016.0041","DOIUrl":"https://doi.org/10.1089/aivt.2016.0041","url":null,"abstract":"<p><p>Approximately 1 million women smoke during pregnancy despite evidence demonstrating serious juvenile and/or adult diseases being linked to early-life exposure to cigarette smoke. Susceptibility could be determined by factors in previous generations, that is, prenatal or \"maternal\" exposures to toxins. Prenatal exposure to airborne pollutants such as mainstream cigarette smoke has been shown to induce early-life insults (i.e., gene changes) in Offspring that serve as biomarkers for disease later in life. In this investigation, we have evaluated genome-wide changes in the lungs of mouse Dams and their juvenile Offspring exposed prenatally to mainstream cigarette smoke. An additional lung model was tested alongside the murine model, as a means to find an alternative <i>in vitro</i>, human tissue-based replacement for the use of animals in medical research. Our toxicogenomic and bio-informatic results indicated that <i>in utero</i> exposure altered the genetic patterns of the fetus, which could put them at greater risk for developing a range of chronic illnesses in later life. The genes altered in the <i>in vitro</i>, cell culture model were reflected in the murine model of prenatal exposure to mainstream cigarette smoke. The use of alternative <i>in vitro</i> models derived from human medical waste tissues could be viable options to achieve human endpoint data and conduct research that meets the remits for scientists to undertake the 3Rs practices.</p>","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 4","pages":"379-388"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2016.0041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36901704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In VitroHuman Airway Models for Study of Goblet Cell Hyperplasia and Mucus Production: Effects of Th2 Cytokines, Double-Stranded RNA, and Tobacco Smoke","authors":"Jennifer Bolmarcich, Sibylle Wilbert, G. Jackson, J. Oldach, M. Bachelor, T. Kenney, C. Wright, P. Hayden","doi":"10.1089/aivt.2017.0001","DOIUrl":"https://doi.org/10.1089/aivt.2017.0001","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60778445","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}

{"title":"Perspectives on <i>In Vitro</i> to <i>In Vivo</i> Extrapolations.","authors":"Thomas Hartung","doi":"10.1089/aivt.2016.0026","DOIUrl":"https://doi.org/10.1089/aivt.2016.0026","url":null,"abstract":"<p><p>Quantitative <i>in vitro</i> to <i>in vivo</i> extrapolation (QIVIVE) is broadly considered a prerequisite bridge from <i>in vitro</i> findings to a dose paradigm. Quality and relevance of cell systems are the first prerequisite for QIVIVE. Information-rich and mechanistic endpoints (biomarkers) improve extrapolations, but a sophisticated endpoint does not make a bad cell model a good one. The next need is reverse toxicokinetics (TK), which estimates the dose necessary to reach a tissue concentration that is active <i>in vitro</i>. The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) has created a roadmap for animal-free systemic toxicity testing, in which the needs and opportunities for TK are elaborated, in the context of different systemic toxicities. The report was discussed at two stakeholder forums in Brussels in 2012 and in Washington in 2013; the key recommendations are summarized herein. Contrary to common belief and the Paracelsus paradigm of everything is toxic, the majority of industrial chemicals do not exhibit toxicity. Strengthening the credibility of negative results of alternative approaches for hazard identification, therefore, avoids the need for QIVIVE. Here, especially the combination of methods in integrated testing strategies is most promising. Two further but very different approaches aim to overcome the problem of modeling <i>in vivo</i> complexity: The <i>human-on-a-chip</i> movement aims to reproduce large parts of living organism's complexity via microphysiological systems, that is, organ equivalents combined by microfluidics. At the same time, the Toxicity Testing in the 21st Century (Tox-21c) movement aims for mechanistic approaches (adverse outcome pathways as promoted by Organisation for Economic Co-operation and Development (OECD) or pathways of toxicity in the Human Toxome Project) for high-throughput screening, biological phenotyping, and ultimately a systems toxicology approach through integration with computer modeling. These 21st century approaches also require 21st century validation, for example, by evidence-based toxicology. Ultimately, QIVIVE is a prerequisite for extrapolating Tox-21c such approaches to human risk assessment.</p>","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 4","pages":"305-316"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2016.0026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37503064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Liver Biology and the Tissue Response to Injury in Bioprinted Human Liver Tissues","authors":"K. Retting, Dwayne E Carter, Candace Crogan-Grundy, C. Khatiwala, L. Norona, Elizabeth Paffenroth, U. Hanumegowda, Alice Chen, L. Hazelwood, L. Lehman-Mckeeman, S. Presnell","doi":"10.1089/aivt.2018.0015","DOIUrl":"https://doi.org/10.1089/aivt.2018.0015","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2018.0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60778619","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}

{"title":"Profiling Acute Oral and Inhalation Toxicity Data Using a Computational Workflow to Screen for Facile Chemical Reactivity","authors":"Daniel M. Wilson, Sanjeeva J. Wijeyesakere, Amanda K. Parks, T. Auernhammer, S. Krieger, J. Hotchkiss, M. S. Marty","doi":"10.1089/aivt.2017.0041","DOIUrl":"https://doi.org/10.1089/aivt.2017.0041","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60778527","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}

{"title":"Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway <i>In Vitro</i> Human Airway Model.","authors":"George R Jackson,&nbsp;Anna G Maione,&nbsp;Mitchell Klausner,&nbsp;Patrick J Hayden","doi":"10.1089/aivt.2018.0004","DOIUrl":"https://doi.org/10.1089/aivt.2018.0004","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (<i>in vitro</i>) test for determining acute inhalation toxicity using the EpiAirway™ <i>in vitro</i> human airway model as a potential alternative for currently accepted animal tests. <b><i>Materials and Methods:</i></b> The <i>in vitro</i> test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The <i>in vitro</i> toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. <b><i>Results:</i></b> The EpiAirway prediction model identified <i>in vivo</i> rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. <b><i>Conclusions:</i></b> These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.</p>","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 2","pages":"149-158"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2018.0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36224884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal Testing for Acute Inhalation Toxicity: A Thing of the Past?","authors":"Emilie Da Silva, J. Sørli","doi":"10.1089/AIVT.2017.0037","DOIUrl":"https://doi.org/10.1089/AIVT.2017.0037","url":null,"abstract":"Abstract According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403, TG 436, and TG 433). Since animal testing is ethically, scientifically and economically questionable, adoption of alternative methods by the European Union and the OECD is needed. An in vitro system based on the study of lung surfactant function is introduced.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/AIVT.2017.0037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42679029","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}