942 results match your criteria ALTEX[Journal]
ALTEX 2018 Nov 28. Epub 2018 Nov 28.
Scientific Direction Chemical and Physical Health Risks, Sciensano, Brussels, Belgium.
Due to the exponentially growing number of substances requiring safety evaluation, efficient prioritisation strategies are needed to identify those of highest concern. To limit unnecessary animal testing, such strategies should respect the 3R principles (Replacement, Reduction, Refinement). In the present study, a strategy based on non-animal approaches was developed to prioritize non-evaluated printed paper and board food contact material (FCM) substances for further in-depth safety evaluation. Read More
ALTEX 2018 Nov 27. Epub 2018 Nov 27.
Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Austria.
Chemical UV-filters are frequently applied as active ingredients in sunscreen to protect from detrimental effects of UV radiation. Regardless, many of these compounds are not well characterized concerning their capacity to counteract UV induced reactive oxygen species (ROS). Intracellular ROS release is an early event upon UV exposure and a crucial trigger of reaction cascades that may provoke adverse effects both in short- and long-term. Read More
ALTEX 2018 Nov 23. Epub 2018 Nov 23.
Institute of Anatomy, Charles University, Prague, Czech Republic.
Using scaffolds with appropriate porosity represents a potential approach for repair of critical-size bone defects. Vascularization is essential for bone formation and healing. This study investigates methods for monitoring angiogenesis within porous biopolymer scaffolds on the basis of polyhydroxybutyrate (PHB)/chitosan. Read More
ALTEX 2018 Nov 21. Epub 2018 Nov 21.
RIKILT Wageningen University & Research, Wageningen, The Netherlands.
The mouse bioassay for the detection of marine biotoxins in shellfish products is 40 years old and still in use. A full ban or total replacement of this in vivo test has been postponed because of the fear that current chemical-based detection methods could miss a new emerging toxin. In order to fully replace the mouse bioassay, more efforts are needed on the search for functional assays with specific endpoints. Read More
ALTEX 2018 Nov 19. Epub 2018 Nov 19.
National Institutes for Food and Drug Control, Beijing, China.
ALTEX 2018 Nov 19. Epub 2018 Nov 19.
Laboratory of Molecular Oncology.
Despite widely used for basic and preclinical studies in dermatology, available animal models only partly recapitulate human skin features often leading to disappointing outputs when preclinical results are translated to the clinic. Therefore, the need to develop alternative, non-animal models is widely recognized to more closely recapitulate human skin pathophysiology and to address the pressing ethical demand of reducing the number of animals used for research purposes, following the globally accepted 3Rs principle (Replacement, Reduction and Refinement). Skin is the outermost organ of the body, and, as such, easily accessible. Read More
ALTEX 2018 Nov 10. Epub 2018 Nov 10.
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
There is a need for fast, efficient, and cost-effective hazard identification and characterization of chemical hazards. This need is generating increased interest in the use of zebrafish embryos as both a screening tool and an alternative to mammalian test methods. A Collaborative Workshop on Aquatic Models and 21st Century Toxicology identified the lack of appropriate and consistent testing protocols as a challenge to the broader application of the zebrafish embryo model. Read More
ALTEX 2018 Oct 29. Epub 2018 Oct 29.
Helmholtz Centre for Environmental Research - UFZ, Department of Bioanalytical Ecotoxicology, Leipzig, Germany.
The zebrafish embryo test has been discussed as an alternative test system to provide data on acute fish toxicity required by diverse regulations. A meta-analysis of zebrafish embryo acute toxicity (ZFET) data has revealed conflicting evidence that narcotic compounds (i.e. Read More
ALTEX 2018 ;35(4):520-521
Dipartimento Ambiente e Salute, Istituto Superiore di Sanità, Rome, Italy.
ALTEX 2018 ;35(4):518-519
Animal Welfare Academy, German Animal Welfare Federation, Neubiberg, Germany.
ALTEX 2018 ;35(4):516-517
Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.
ALTEX 2018 Oct 16. Epub 2018 Oct 16.
US Army Engineer Research and Development Center, Vicksburg, MS, USA.
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. Read More
ALTEX 2018 Oct 10. Epub 2018 Oct 10.
European Coalition to End Animal Experiments, London, UK.
There have been significant developments in the use of animals to test Botulinum toxin products in Europe in recent years. This paper summarises and discusses these from the perspective of the animal protection organisation. A cell-based assay has been validated by Allergan and is now being used for the replacement of the mouse bioassay for the batch testing of their Botulinum toxin A products. Read More
ALTEX 2018 Oct 9. Epub 2018 Oct 9.
Experimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Therapeutic agents that are used by patients with rheumatic and musculoskeletal diseases were originally developed and tested in animal models, and although retrospective studies show a limited predictive value, it could be explained by the fact that there are no good in vitro alternatives. In this study, we developed a 3-dimensional synovial membrane model made of either human primary synovial cell suspensions or a mix of primary fibroblast-like synoviocytes and CD14+ mononuclear cells. We analyzed the composition of the mature micromasses by immunohistochemical staining and flow cytometry and show that the outer surface forms a lining layer consisting out of fibroblast-like and macrophage-like cells, reflecting the in vivo naïve synovial membrane. Read More
ALTEX 2018 Sep 14. Epub 2018 Sep 14.
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Pain has a profound effect on an animal's wellbeing. In Germany, researchers using animals have been legally required since 1972 to reduce any possible pain, suffering, distress or lasting harm to an absolute minimum. To evaluate how these provisions have been implemented in practice, an assessment of refinements to experimental techniques was conducted by retrospectively reviewing 684 surgical interventions described in 506 animal research applications that were sent to the German competent authorities for approval in 2010. Read More
ALTEX 2018 Aug 3. Epub 2018 Aug 3.
Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
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. Read More
ALTEX 2018 27;35(4):435-440. Epub 2018 Jul 27.
Diabetes, Obesity, and Wellness Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cell culture has enhanced our understanding of cellular physiology and constitutes an important tool in advancing mechanistic insight. Researchers should be reminded, however, that there are limitations in extrapolating data derived from cultured cells to questions focusing on the impact of sex. In this Opinion, we highlight two underappreciated aspects of cell culture systems regarding sex: how cell culture media alters the sex hormone environment, and how the innate sex of the cell is often not factored into the overall analysis. Read More
ALTEX 2018 Jul 12. Epub 2018 Jul 12.
EU Commission Joint Research Centre (JRC), Ispra, Italy.
The replacement of animals in acute systemic toxicity testing remains a considerable challenge. Only animal data are currently accepted by regulators, including data generated by reduction and refinement methods. The development of Integrated Approaches to Testing and Assessment (IATA) is hampered by an insufficient understanding of the numerous toxicity pathways that lead to acute systemic toxicity. Read More
ALTEX 2018 12;35(4):489-494. Epub 2018 Jul 12.
Boehringer-Ingelheim, Lyon, France.
Titration of foot-and-mouth disease cattle challenge virus in cattle tongue has been the standard for many years in many countries, although titration in animals has been replaced by in vitro methods for all other applications. The objective of the analysis was the replacement of in vivo titration of cattle challenge virus by in vitro titration. Using data from 32 in vivo titration experiments together with the in vitro titration results of the same samples obtained by plaque count on primary lamb or pig kidney cells, as well as data from the virus isolation control chart used in the laboratory, we show that the reproducibility of the in vitro titration is much higher than that of the in vivo titration. Read More
ALTEX 2018 ;35(3):429-432
Leibniz Research Centre for Working Environment and Human Factors (IfADo), Technical University of Dortmund, Dortmund, Germany.
Methods papers are important for the progress of biomedical research, as they provide the essential tools to explore new questions and help to better answer old ones. However, it is often not clear how a methods paper differs from a methods protocol. Confusion between these two very different types of publication is widespread. Read More
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
Swiss Animal Protection (SAP), Basle, Switzerland.
Università degli Studi di Milano, Department of Veterinary Medicine (DIMEVET), Milan, Italy.
Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
ALTEX 2018 ;35(3):275-305
Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
For a long time, the discussion about animal testing vs its alternatives centered on animal welfare. This was a static warfare, or at least a gridlock, where life scientists had to take a position and make their value choices and hardly anyone changed sides. Technical advances have changed the frontline somewhat, with in vitro and in silico methods gaining more ground. Read More
ALTEX 2018 8;35(4):504-515. Epub 2018 Jul 8.
Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
The role of megalin in the regulation of renal vitamin D homeostasis has previously been evaluated in megalin-knockout mice and rat proximal tubule epithelial cells. We revisited these hypotheses that were previously tested solely in rodent models, this time using a 3-dimensional proximal tubule microphysiological system incorporating primary human proximal tubule epithelial cells. Using this human cell-derived model, we confirmed that 25OHD3 is transported into the human proximal tubule epithelium via megalin-mediated endocytosis while bound to vitamin D binding protein. Read More
ALTEX 2018 8;35(4):441-452. Epub 2018 Jul 8.
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
Assessing inter-individual variability in responses to xenobiotics remains a substantial challenge, both in drug development with respect to pharmaceuticals and in public health with respect to environmental chemicals. Although approaches exist to characterize pharmacokinetic variability, there are no methods to routinely address pharmacodynamic variability. In this study, we aimed to demonstrate the feasibility of characterizing inter-individual variability in a human in vitro model. Read More
ALTEX 2018 ;35(2):268-271
In vitro Toxicology and Biomedicine, Dept inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Konstanz, Germany.
Many types of assays in cell biology, pharmacology and toxicology generate data in which a parameter is measured in a reference system (negative control) and then also under conditions of increasing stress or drug exposure. To make such data easily comparable, they are normalized, i.e. Read More
ALTEX 2018 13;35(4):477-488. Epub 2018 Jun 13.
XCellR8 Ltd, The Innovation Centre, Sci-Tech Daresbury, Daresbury, Cheshire, UK.
Skin sensitisers are substances that can elicit allergic responses following skin contact and the process by which this occurs is described as skin sensitisation. Skin sensitisation is defined as a series of key events, that form an adverse outcome pathway (AOP). Key event three in the AOP is dendritic cell activation that can be modelled by the human Cell Line Activation Test (h-CLAT) and is typified by changes in cell surface markers CD54 and CD86 in dendritic cells. Read More
ALTEX 2018 13;35(4):464-476. Epub 2018 Jun 13.
Reutlingen University, Reutlingen, Germany.
Vascularized adipose tissue models are highly demanded as alternative to existing animal models to elucidate the mechanisms of widespread diseases, screen for new drugs or asses corresponding safety levels. Standardly used animal-derived sera therein, are associated to ethical concerns, the risk of contaminations and many uncertainties in their composition and impact on cells. Therefore their use should be completely omitted. Read More
ALTEX 2018 14;35(4):453-463. Epub 2018 Jun 14.
Medtronic plc, Minneapolis, MN, USA.
Pyrogenicity presents a challenge to clinicians, medical device manufacturers, and regulators. A febrile response may be caused by endotoxin contamination, microbial components other than endotoxin, or chemical agents that generate a material-mediated pyrogenic response. While test methods for the assessment of endotoxin contamination and some microbial components other than endotoxin are well-established, material-mediated pyrogens remain elusively undefined. Read More
ALTEX 2018 28;35(3):397-412. Epub 2018 May 28.
Higher School of Economics, Moscow, Russia.
Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. Read More
ALTEX 2018 13;35(3):390-396. Epub 2018 Apr 13.
Translational Center Regenerative Therapies, Fraunhofer Institute for Silicate Research, Würzburg, Germany.
To protect the human skin from extensive solar radiation, melanocytes produce melanin and disperse it via melanosomes to keratinocytes in the basal and suprabasal layers of the human epidermis. Moreover, melanocytes are associated with pathological skin conditions such as vitiligo and psoriasis. Thus, an in vitro skin model that comprises a defined cutaneous pigmentation system is highly relevant in cosmetic, pharmaceutical and medical research. Read More
ALTEX 2018 13;35(3):353-378. Epub 2018 Apr 13.
CAAT-Europe, University of Konstanz, Konstanz, Germany.
A major reason for the current reproducibility crisis in the life sciences is the poor implementation of quality control measures and reporting standards. Improvement is needed, especially regarding increasingly complex in vitro methods. Good Cell Culture Practice (GCCP) was an effort from 1996 to 2005 to develop such minimum quality standards also applicable in academia. Read More
ALTEX 2018 ;35(2):254-256
Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy.
ALTEX 2018 ;35(2):256-257
LARF-DIMES, Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy.
ALTEX 2018 ;35(2):258-260
EPISKIN Academy, Lyon, France.
ALTEX 2018 ;35(2):260-261
Centro 3R (Interuniversity Center for the Promotion of 3Rs Principles in Teaching and Research), Italy.
ALTEX 2018 ;35(2):139-162
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA.
A biological system is more than the sum of its parts - it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e. Read More
ALTEX 2018 12;35(3):379-389. Epub 2018 Mar 12.
BASF SE Global Environmental & Consumer Safety, Crop Protection, Limburgerhof, Germany.
The approving agencies for plant protection agents request xenobiotic metabolism and residue studies in rats, farm animals and plants (e.g. EU regulation 1107/2009) according to OECD guidelines. Read More
ALTEX 2018 11;35(4):495-503. Epub 2018 Mar 11.
CICS, UBI - Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.
The HET-CAM (Hen’s Egg Test-Chorioallantoic Membrane) assay is an in vitro alternative to the in vivo Draize rabbit eye test. This qualitative method assesses the irritancy potential of chemicals. The chorioallantoic membrane responds to injury with an inflammatory process similar to that in the rabbit eye’s conjunctival tissue. Read More
ALTEX 2018 8;35(2):163-168. Epub 2018 Mar 8.
National Center for Toxicological Research, Food and Drug Administration, Silver Spring, MD, USA.
The traditional approaches to toxicity testing have posed multiple challenges for evaluating the safety of commercial chemicals, pesticides, food additives/contaminants, and medical products.The challenges include number of chemicals that need to be tested, time and resource intensive nature of traditional toxicity tests, and unexpected adverse effects that occur in pharmaceutical clinical trials despite the extensive toxicological testing.Over a decade ago, the U. Read More
ALTEX 2018 23;35(3):306-352. Epub 2018 Feb 23.
Center for Alternatives to Animal Testing, CAAT-Europe, University of Konstanz, Konstanz, Germany.
Multiple non-animal-based test methods have never been formally validated. In order to use such new approach methods (NAMs) in a regulatory context, criteria to define their readiness are necessary. The field of developmental neurotoxicity (DNT) testing is used to exemplify the application of readiness criteria. Read More
ALTEX 2018 21;35(2):235-253. Epub 2018 Jan 21.
In vitro Toxicology and Biomedicine, Dept inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
The (developmental) neurotoxicity hazard is still unknown for most chemicals. Establishing a test battery covering most of the relevant adverse outcome pathways may close this gap, without requiring a huge animal experimentation program. Ideally, each of the assays would cover multiple mechanisms of toxicity. Read More
ALTEX 2018 ;35(1):124-126
Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
ALTEX 2018 ;35(1):123-125
Société Française de Pharmacie de la Méditerrannée Latine, Saint Genis-Laval, France.
ALTEX 2018 ;35(1):121-122
European Chemicals Agency (ECHA), Helsinki, Finland.
ALTEX 2018 ;35(1):119-121
BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
ALTEX 2018 ;35(1):3-25
Johns Hopkins Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA.
The US Food and Drug Administration (FDA) has premarket review authority over food additives, but a food manufacturer may, according to the legislation, intentionally add a substance to human food or animal food without their premarket review or approval if the substance is generally recognized, among qualified experts, to be safe under the conditions of its intended use. Generally recognized as safe (GRAS) implies that the current scientific community agrees on the adequacy of how data is generated. This system has come under public pressure because of doubts as to its efficiency and the FDA's recent GRAS rule is part of the response. Read More
ALTEX 2018 2;35(2):223-234. Epub 2017 Dec 2.
Human and Environmental Toxicology, Department of Biology, University of Konstanz, Konstanz, Germany.
The proximal tubule is the primary site for renal solute reabsorption and secretion and thus a main target for drug-induced toxicity. Current nonclinical methods using 2D cell cultures are unable to fully recapitulate clinical drug responses mainly due to limited in vitro functional lifespan. Since extracellular matrices are known to be key regulators of cell development, culturing cells on classic 2D plastic surfaces inevitably results in loss of differentiation. Read More