ATLA 41.2, May 2013

//ATLA 41.2, May 2013

ATLA Volume 41, Issue 2

Definition of the Applicability Domain of the Short Time Exposure (STE) Test for Predicting the Eye Irritation of Chemicals

Kazuhiko Hayashi, Takayuki Abo, Yuko Nukada and Hitoshi Sakaguchi

The Short Time Exposure (STE) test is a simple and easy-to-perform in vitro eye irritation test, that uses the viability of SIRC cells (a rabbit corneal cell line) treated for five minutes as the endpoint. In this study, our goal was to define the applicability domain of the STE test, based on the results obtained with a set of 113 substances. To achieve this goal, chemicals were selected to represent both different chemical classes and different chemical properties, as well as to cover, in a balanced manner, the categories of eye irritation potential according to the Globally Harmonised System (GHS). Accuracy analysis indicated that the rates of false negatives for organic/inorganic salts (75.0%), hydrocarbons (33.3%) and alcohols (23.5%) were high. Many of the false negative results were for solid substances. It is noteworthy that no surfactant resulted in a false negative result in the STE test. Further examination of the physical property data and performance showed a significant improvement in the predictive accuracy, when substances with vapour pressures over 6kPa were excluded from the analyses. Our results indicate that several substances i.e. certain solids such as salts, alcohols, hydrocarbons, and volatile substances with a vapour pressure over 6kPa — do not fall within the applicability domain of the STE test. Overall, we are encouraged by the performance and improved accuracy of the STE test.

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The Use of Genetically-engineered Animals in Science: Perspectives of Canadian Animal Care Committee Members

Elisabeth H. Ormandy, Julie Dale and Gilly Griffin

The genetic engineering of animals for their use in science challenges the implementation of refinement and reduction in several areas, including the invasiveness of the procedures involved, unanticipated welfare concerns, and the numbers of animals required. Additionally, the creation of genetically engineered animals raises problems with the Canadian system of reporting animal numbers per Category of Invasiveness, as well as raising issues of whether ethical limits can, or should, be placed on genetic engineering. A workshop was held with the aim of bringing together Canadian animal care committee members to discuss these issues, to reflect on progress that has been made in addressing them, and to propose ways of overcoming any challenges. Although previous literature has made recommendations with regard to refinement and reduction when creating new genetically-engineered animals, the perception of the workshop participants was that some key opportunities are being missed. The participants identified the main roadblocks to the implementation of refinement and reduction alternatives as confidentiality, cost and competition. If the scientific community is to make progress concerning the implementation of refinement and reduction, particularly in the creation and use of genetically-engineered animals, addressing these roadblocks needs to be a priority.

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Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

Dirk Weisensee, Albrecht Poth, Ewald Roemer, Lynda L. Conroy and Walter K. Schlage

In vitro cell transformation assays detect transformed cells that have acquired the distinct characteristics of malignant cells and thus model one stage of in vivo carcinogenesis. These assays have been proposed as surrogate models for predicting the non-genotoxic carcinogenic potential of chemicals. The Bhas 42 cell transformation assay, a short-term assay that uses v-Ha-ras-transfected Balb/c 3T3 cells, can detect the tumour promoter-like activities of chemicals, but has not previously been used with cigarette smoke. The particulate phase of cigarette smoke (total particulate matter [TPM]) is known to induce tumours in vivo in the mouse skin painting assay. Therefore, we investigated the ability of this Bhas cell assay to form morphologically transformed foci in vitro when repeatedly challenged with TPM from a standard research cigarette. TPM induced a dose-dependent increase in Type III foci, and a significant increase (up to 20-fold) in focus formation at moderately toxic concentrations between 5 and 60μg TPM/ml, with a peak at 20μg/ml. Three batches of TPM were tested in three independent experiments. Precision (repeatability and reproducibility) was calculated by using 0, 5, 10, and 20μg TPM/ml. Repeatability and reproducibility, expressed as the relative standard deviation obtained from the normalised slopes of the dose–response curves, were 17.2% and 19.6%, respectively; the slopes were 0.7402 ± 0.1247, 0.9347 ± 0.1316, and 0.8772 ± 0.1767 (increase factor*ml/mg TPM; mean ± SD); and the goodness of fit (r2) of the mean slopes, each derived from n = 6 repeats, was 0.9449, 0.8198, and 0.8344, respectively. This in vitro assay with Bhas 42 cells, which are regarded as already initiated in the two-stage paradigm of carcinogenesis (initiation and promotion), is able to detect cell transformation induced by cigarette smoke in a dose-dependent manner with a high sensitivity and good precision. Because this assay is fast and yields reliable results, it may be useful in product assessment, as well as for further investigation of the non-genotoxic carcinogenic activity of tobacco smoke-related test substances.

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Progress in Promoting the Three Rs in Korea: Efficiency and Consistency

Byung In Choe, Gwi Hyang Lee, Paul G. Braunschweiger and Lynette A. Hart

The Korea National Information Center for the 3Rs was established in August 2011, to enhance humane science and animal welfare in Korea. It is a national Three Rs platform, with the goal of exchanging knowledge and sharing examples of best practice, in order to help replace laboratory animal use in education and training. This paper briefly summarises the progress made and the challenges that have become apparent during the initial operation of the collaborative project. There is a need to recognise and manage the challenges resulting from policy changes, especially misinterpretation of the objectives by the decision makers at the participating academic institutions and the government. The collective power of this type of collaborative project can be used to leverage an ongoing commitment to essentials such as consistent funding for operational and support staff, as well as allocation of the required space.

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Editorial: When Using Animal Tests or Alternative Methods, We are Also Testing Ourselves

Michael Balls

The correlation between the effects measured in a supposedly useful test with a model system (such as an animal or an in vitro system) and the likely effects in the object of interest (such as a human being) must fall between 50% (the equivalent of tossing a coin, so a relationship below this would be useless) and 100% (which is unattainable, given the inevitably of significant differences between the test system and the object system, and variation in the responses in both of them).
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Nomination of Professor Per Artursson as the recipient of the Björn Ekwall Memorial Award 2013

Erik Walum

Professor Per Artursson (M Sci Pharm, PhD) of the Department of Pharmaceutics at Uppsala University, Sweden, was nominated for the 2013 Björn
Ekwall Memorial Award, in recognition of his scientific achievements in the field of drug design and delivery, and for the innovative design and successful implementation of in vitro methods in pharmacology and pharmaceutical studies.
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News & Views

ATLA staff writer

Dietary Studies with C. elegans
Adult Stem Cells from Intestinal Tissue
Stem Cell-derived Cardiomyocytes as Alternatives to Laboratory Animals
Predicting Side-effects of Chemotherapy Treatment
Culture of Zebrafish Cardiomyocytes
In Vitro Gut Bacterial Adhesion Model
3-D In Vitro Model of Ewing Sarcoma
Flies Used for Studies on Depression
In Vitro Methods for Prion Research
Ex Vivo Bone Model
Harvard to Close Primate Centre
Immune Response Studied In Vitro
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CAAT News & Views

ATLA staff writer

CAAT featured in Nature and Nature Medicine
CAAT 2013–2014 Research Grants
Society of Toxicology Enhancement of Animal Welfare Awarded to Martin L. Stephens
CAAT at the Society of Toxicology Annual Meeting
CAAT at the EU Parliament
Lessons learned, challenges, and opportunities: The US Endocrine Disruptor Screening Program
Developing Microphysiological Systems for Use as Regulatory Tools — Challenges and Opportunities
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IIVS News & Views

ATLA staff writer

EPAA and IIVS Sign Memorandum of Understanding
IIVS Shares Poster Award at EPAA Meeting
COLAMA 2012: 1st Latin American Congress of Alternative Methods for Use of Animals in Education, Research and Industry
IIVS Wins the First LUSH Cosmetics Prize for Training
52nd Annual Meeting of the Society of Toxicology
IIVS International Training Programmes
IIVS International Outreach Program (IOP): Training at Beijing Technology and Business University

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Response to the Comment published in ATLA, on the Declaration on Openness on Animal Research

Concordat on Openness on Animal Research

Over fifty organisations involved in biomedical research in the UK have come together to develop a Concordat on how they can all work to be more open and honest about their use of animals in scientific, medical and veterinary research.
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