ATLA 38, 2010

/ATLA 38, 2010

ECVAM News & Views

ATLA Staff Writer

OECD Test Guideline 487 on the in vitro Micronucleus Test: Progress Toward Regulatory Acceptance
The New ECVAM Scientific Advisory Board and its Next Meeting
ECVAM Expert Pool — Call For Experts is in Preparation
European Partnership on Alternative Approaches to Animal Testing: An ECVAM/EPAA Workshop on the Consistency Approach for Quality Control of Vaccines — A Three Rs Opportunity
Online Publication of the ECVAM Kinetic Parameters DataBase & ECVAM Kinetics Calculation Tool
Recent Publications
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2017-01-09T06:38:01+00:00 Tags: |

News & Views

ATLA Staff Writer

First University in the Russian Ural Region Signs a Formal Agreement on Stopping Animal Experiments
Re-issue of Warning Over Bisphenol A
Increasing the Success Rate of Transplants by Using Biomarkers
New Japanese Content Added to Toxicity Testing Resource Centre
An In Vitro Model of Cerebral Arteries for Use in Stroke Studies
Biomarkers Help Improve Drug Testing and Clinical Trials
Southern African Genome Study
Claims that the Medical Potential of IPS Stem-cells has been Exaggerated
Sharing of Malaria Research Data to Help Fight the Disease
Major Clinical Trials for Childhood Peanut Allergy
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2017-01-09T06:38:02+00:00 Tags: |

Application of the Improved BALB/c 3T3 Cell Transformation Assay to the Examination of the Initiating and Promoting Activities of Chemicals: The Second Interlaboratory Collaborative Study by the Non-genotoxic Carcinogen Study Group of Japan

Toshiyuki Tsuchiya, Makoto Umeda, Noriho Tanaka, Ayako Sakai, Hiroshi Nishiyama, Isao Yoshimura, Syozo Ajimi, Shin Asada, Masumi Asakura, Hiroshi Baba, Yasuaki Dewa, Youji Ebe, Yuichi Fushiwaki, Yuji Hagiwara, Shuichi Hamada, Tetsuo Hamamura, Yumiko Iwase, Yoshitsugu Kajiwara, Yasushi Kasahara, Yukihiko Kato, Masayoshi Kawabata, Emiko Kitada, Kazuko Kaneko, Yuko Kizaki, Kinya Kubo, Daisaku Miura, Kaori Mashiko, Fukutaro Mizuhashi, Dai Muramatsu, Madoka Nakajima, Tetsu Nakamura, Hidetoshi Oishi, Toshiaki Sasaki, Sawako Shimada, Chitose Takahashi, Yuko Takeda, Sinobu Wakuri, Nobuhiro Yajima, Satoshi Yajima and Tomoko Yatsushiro

The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two- stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1μg/ml 12-O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the twostage assay (pretreated with 0.2μg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-β1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative — again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the determination of the maximum dose, are adequately considered. The application of this two-stage assay for screening the initiating and promoting potential of chemicals is recommended for consideration by other research groups and regulatory authorities.
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An Estimation of the Extent of Animal Use in Research in Brazil, as Determined by Bibliographic Sampling from Journals Published in the State of Paraná

Vanessa Carli Bones Silla, Elaine Cristina de Oliveira Sans and Carla Forte Maiolino Molento

Animal use in research is an issue of increasing ethical concern. The objective of this work was to investigate animal use in research described in the papers appearing in 18 journals published in the State of Paraná in 2006. The fields used in the bibliographic sampling were: agrarian science, biological science, biological and health science, environmental science, food technology, and health science. Of the 865 papers analysed, 41% involved the use of animals — a total of 3,497,653 animals, of which 216,223 were vertebrates. Procedures which were classified as A or B for degree of invasiveness were involved in 67% of the papers; 571 fish were employed in procedures classified as E. Only 11% of the journals required certificates from Animal Use Ethics Committees. These results suggest that Brazil is important in the context of worldwide animal use for research, in terms of both the total numbers of animals and the numbers of vertebrates used. Bibliographical sampling is a useful method for estimating the extent of animal use in experiments in Brazil. However, there are limitations to this approach, resulting from the geographical distribution of the authors, the existence of papers presenting insufficient information, and the exclusive inclusion of animal experimentation that actually reaches publication. Thus, the introduction of a formal system to record and control laboratory animal use in Brazil, is urgently required.
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Experience with the HET-CAM Method in the Routine Testing of a Broad Variety of Chemicals and Formulations

Arnhild Schrage, Armin O. Gamer, Ben van Ravenzwaay and Robert Landsiedel

Data on eye irritation are generally needed for the hazard identification of chemicals. For the routine testing of a broad variety of chemicals and formulations, we have used the Hen’s Egg Test- Chorioallantoic Membrane (HET-CAM) method. In the course of a tiered-testing strategy, and due to the lack of global regulatory acceptance of the HET-CAM method, we have also performed the Rabbit Eye Irritation test according to OECD Test Guideline 405. Of the 145 substances tested, 76% were classified as non-irritant/mild irritant and 13% were identified as irritant in vivo, according to the EU classification system (61% and 28%, respectively, with the GHS classification). The remaining 11% were severe irritants in vivo, based on the irreversibility of the effects and not due to sufficiently high irritation scores in the three days following application. The retrospective analysis revealed that the overall accuracy of the HET-CAM assay was 65% and the overall rates of false-negatives (FN) and false-positives (FP) were 50% and 33%, respectively. The HET-CAM assay was sufficiently specific (few FP) for water-soluble substances, but failed to identify nearly all the severe irritants within this group. In contrast, it was highly sensitive (no FN) for non-soluble and oil-soluble substances, but the specificity for this group was rather low. Therefore, we conclude that the HET-CAM assay is not useful in our tiered-testing strategy for eye irritation testing. However, for water-insoluble substances, it might be applicable in combination with another in vitro method, provided that regulatory acceptance is gained.
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Laboratory Animal Science in China: Current Status and Potential for the Adoption of Three R Alternatives

Qi Kong and Chuan Qin

This paper aims to describe the development of laboratory animal science in China on the basis of historical evidence and recent national survey data, and to identify the problems facing the adoption of Three R alternatives. The authors undertook a national survey in 2006, by means of a questionnaire sent to 31 provinces, municipalities and autonomous regions, and also compared data from a variety of sources, including several national surveys and published papers. Laboratory animal science in China has developed rapidly over the past 30 years, as a result of a combination of economic, governmental and societal forces. More than 100,000 people work in the field of laboratory animal science, in 2,000 laboratory animal centres, institutes, universities, organisations, and companies. During the year of our survey, more than 19 million laboratory animals were produced from 320 licensed production facilities. Approximately 16 million laboratory animals were used in animal experiments, in 1530 facilities licensed for their use. The scale of the market for the supply and use of laboratory animals is huge, and thus it is very important to improve the level of adoption of these alternatives, in education, research and testing. For China, this presents a significant economic and technological opportunity in the field of biosciences research. The concept of the Three Rs first appeared in China in the 1980s, when the scale of laboratory animal sciences was starting to increase. In the 1990s, the Three Rs concept became commonly accepted among laboratory animal scientists, and began to appear in government documents. In the first decade of the 21st century, the Three Rs principles have become increasingly applied in our day-to-day work. But further time is still needed to achieve the full application of the Three Rs principles, especially the adoption of Three R alternatives. This paper describes the achievements in China relating to laboratory animal science, the use of Three R alternatives, and animal welfare, and shows that there is currently great potential for the adoption of alternatives. The information will help scientists and organisations around the world to gain better insight into the current state of laboratory animal science in China, and hopefully, will enable them to give advice on how we can improve the adoption of Three R alternatives in our country.
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The Use of Organotypic Hippocampal Slice Cultures to Evaluate Protection by Non-competitive NMDA Receptor Antagonists Against Excitotoxicity

Avi Ring, Rita Tanso and Jens Noraberg

There is great interest in testing neuroprotectants which inhibit the neurodegeneration that results from excessive activation of N-methyl-D-aspartate (NMDA) receptors. As an alternative to in vivo testing in animal models, we demonstrate here the use of a complex in vitro model to compare the efficacy and toxicity of NMDA receptor inhibitors. Organotypic hippocampal slice cultures were used to compare the effectiveness of the Alzheimer’s disease drug, memantine, the Parkinson’s disease drug, procyclidine, and the novel neuroprotectant, gacyclidine (GK11), against NMDA-induced toxicity. All three drugs are non-competitive NMDA receptor open-channel blockers that inhibit excitotoxic injury, and their neuroprotective capacities have been extensively investigated in vivo in animal models. They have also been evaluated as potential countermeasure agents against organophosphate poisoning. Quantitative densitometric image analysis of propidium iodide uptake in hippocampal regions CA1, CA3 and DG, showed that, after exposure to 10μM NMDA for 24 hours, GK11 was the most potent of the three drugs, with an IC50 of about 50nM and complete protection at 250nM. When applied at high doses, GK11 was still the more potent neuroprotectant, and also the least cytotoxic. These findings are consistent with those from in vivo tests in rodents. We conclude that the slice culture model provides valuable pre-clinical data, and that applying the model to the screening of neuroprotectants might significantly limit the use of in vivo tests in animals
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Kristie Sullivan, Erin Hill

We invite your readers to support a new scientific society dedicated to the advancement of in vitro, in silico, and other toxicological testing methods, especially as replacements for animal-based tests. The American Society for Cellular and Comp - utational Toxicology (ASCCT) aims to build on the success of similar societies outside the Americas and the growing interest in advancing toxicology for practical, scientific, and ethical reasons.
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2017-01-09T06:38:03+00:00 Tags: |