ATLA 40, 2012

/ATLA 40, 2012

ATLA Volume 40 , published 2012

The Comparability of In Vitro and Ex Vivo Studies on the Percutaneous Permeation of Topical Formulations Containing Ibuprofen

Jessica Stahl, Bettina Blume, Silvia Bienas1 and Manfred Kietzmann

In order to avoid in vivo experiments and to gain information about the suitability of surrogates for skin replacement, Franz-type diffusion cell experiments were conducted by using three ibuprofen containing formulations (cream, gel and microgel) on bovine split-skin samples and cellophane membranes. Moreover, ex vivo examinations were performed on the isolated perfused bovine udder, to study the comparability of in vitro and ex vivo experimental set-ups. Depending on the formulation, noticeable differences in the permeation of Ibuprofen occurred in vitro (udder skin) and ex vivo (isolated perfused bovine udder), but not in the cellophane membrane. The rates of ibuprofen permeability (cream > gel > microgel) and adsorption into the skin (gel > microgel > cream) varied with the formulation, and were probably caused by differences in the ingredients. Furthermore, different storage conditions and seasonal variation in the collection of the skin samples probably led to differences in the amounts of ibuprofen adsorption apparent in the isolated bovine udder and udder skin. In vitro diffusion experiments should be preferred to experiments on isolated organs with regard to the costs involved, the throughput, and the intensity of labour required, unless metabolism of the drug in the skin, or cell–cell interactions are of particular interest.
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Refinement of the Charcoal Meal Study by Reduction of the Fasting Period

Helen Prior, Lorna Ewart, Jonathan Bright and Jean-Pierre Valentin

The aim of this investigation was to determine whether a shorter fasting period than the one historically employed for the charcoal meal test, could be used when measuring gastric emptying and intestinal transit within the same animal, and to ascertain whether the scientific outcome would be affected by this benefit to animal welfare. Rats and mice were fasted for 0, 3, 6 or 18 hours before the oral administration of vehicle or atropine. One hour later, the animals were orally administered a charcoal meal, then 20 minutes later, they were killed and the stomach and small intestine were removed. Intestinal transit time (the position of the charcoal front as a percentage of the total length of the small intestine) and relative gastric emptying (weight of stomach contents) were measured. Rats and mice fasted for six hours showed results for gastric emptying and intestinal transit which were similar to those obtained in animals fasted for 18 hours. Reducing the fasting period reduced the body weight loss in both species, and mice on shorter fasts could be group-housed, as hunger-induced fighting was lessened. Therefore, a fasting period of six hours was subsequently adopted for charcoal meal studies at our institution.
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Comments on UK Options for Transposition of European Directive 2010/63/EU

Michael Balls and Michelle Hudson

The British Government’s proposals for the transposition of European Directive 2010/63/EU are discussed under five main headings: direct transposition without major effects on the UK legislation, introduction of stricter requirements in the Directive, retention of stricter controls in the Animals [Scientific Procedures] Act 1986, questions requiring further consideration, and matters of concern. The Home Office had published a consultation on the options in 2011, which resulted in 98 responses from organisations and 13,458 responses from individuals. Our main concerns relate to the use of non-human primates, the annual publication of the UK statistics on laboratory animal use, and the provision of greater transparency on how animals are used, and why. Finally, we conclude that the new Directive and its transposition into the national laws of the Member states provide a renewed opportunity for genuine commitment to the Three Rs, leading to progressive and significant Reduction, Refinement and Replacement.
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2017-01-09T06:38:42+00:00 Tags: |

Cell Transformation Assays: Are We Barking Up the Wrong Tree?

Robert D. Combes

There has been a current resurgence of interest in the use of cell transformation for predicting carcinogenicity, which is based mainly on rodent carcinogenicity data. In view of this renewed interest, this paper critically reviews the published literature concerning the ability of the available assays to detect IARC Group 1 agents (known human carcinogens) and Group 2A agents (probable human carcinogens). The predictivity of the available assays for human and rodent non-genotoxic carcinogens (NGCs), in comparison with standard and supplementary in vitro and in vivo genotoxicity tests, is also discussed. The principal finding is that a surprising number of human carcinogens have not been tested for cell transformation across the three main assays (SHE, Balb/c 3T3 and C3H10T1/2), confounding comparative assessment of these methods for detecting human carcinogens. This issue is not being addressed in the ongoing validation studies for the first two of these assays, despite the lack of any serious logistical issues associated with the use of most of these chemicals. In addition, there seem to be no plans for using exogenous bio-transformation systems for the metabolic activation of pro-carcinogens, as recommended in an ECVAM workshop held in 1999. To address these important issues, it is strongly recommended that consideration be given to the inclusion of more human carcinogens and an exogenous source of xenobiotic metabolism, such as an S9 fraction, in ongoing and future validation studies. While cell transformation systems detect a high level of NGCs, it is considered premature to rely only on this endpoint for screening for such chemicals, as recently suggested. This is particularly important, in view of the fact that there is still doubt as to the relevance of morphological transformation to tumorigenesis in vivo, and the wide diversity of potential mechanisms by which NGCs are known to act. Recent progress with regard to increasing the objectivity of scoring the transformed phenotype, and prospects for developing human cell-based transformation assays, are reviewed.
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News & Views

ATLA staff writer

Drosophila as a Model for Ayurvedic Medicine
Organ On-a-chip
Neonatal Tissue Culture Model for Vaccine Testing
Endothelial Cells Show Differences
Non-invasive Genotyping of Animals
Brain Tumour Biomarkers Identified
Immune Differences Between Mice and Humans
Computer Model to Predict Side-effects
Cholesterol Research with Zebrafish
Selected ATLA Papers Available on InterNICHE Database
Translation of The Principles into Japanese
Creating 3-D Chips with Human Cells and Tissues

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CAAT News & Views

ATLA staff writer

CAAT-led Consortium to Receive $800,000 Funding for Novel (Developmental) Neurotoxicity Cell Model from NIH
CAAT Pharmaceuticals Information Day — Scientific and Animal Welfare Innovations in Drug Development and Safety Assessment
CAAT Special Lecture by Jesse L. Goodman, MD, MPH, Deputy Commissioner for Science and Public Health of the US Food and Drug Administration
Why Europe Needs the Human Toxome Project
CAAT Information Day: New Approaches to Assessing Countermeasures to Bioterrorism Agents
Kick-off Meeting of the Evidence-based Toxicology Collaboration (EBTC) Europe
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News from the FAL

Rita Seabra

The FRAME Alternatives Laboratory (FAL) was founded in 1983 at the University of Nottingham Medical School. Now under the leadership of Dr Andy Bennett, the FAL is continuing to discover and develop real alternatives to the use of animals in research and testing. Here, Andy outlines another of his current key projects, in a discussion with Rita Seabra.
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2017-01-09T06:38:43+00:00 Tags: |