ATLA 28.1, January 2000

//ATLA 28.1, January 2000

News & Views

ATLA Staff Writer

Experimental Animal Use in Germany
Chimps in HIV Experiments
Training in Alternatives
Cell Test for Shellfish Toxins
1997 Canadian Animal Use Statistics
Emerging Biotechnologies and the Animals (Scientific Procedures) Act 1986
ECACC/Sigma-Aldrich Agreement
HSUS Animals & Society Course Awards
Coordinating Research on the Three Rs
APC on Openness and Animal Procedures
Staff Changes in the Editorial Office
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2017-01-09T06:27:03+00:00 Tags: |

Development of a Decision Support System for the Introduction of Alternative Methods into Local Irritancy/Corrosivity Testing Strategies. Development of a Relational Database

Ingrid Gerner, Gabriele Graetschel, Jürgen Kahl and Eva Schlede

For new chemical substances that are notified within the European Union, data sets have to be submitted to the National Competent Authorities. The data submitted have to demonstrate the physicochemical and toxic properties of the new chemical, such as solubility, partition coefficients and spectra, as well as acute toxic properties and the potential to cause local irritant or corrosive effects. In order to minimise testing for notification purposes (for example, animal testing), it is necessary to develop stepwise assessment procedures, including structure-activity considerations, alternative methods (for example, in vitro tests), and computerised structure-activity relationship (SAR) models. An electronic database was developed which contains physicochemical and toxicological data on approximately 1300 chemical substances. It is used for regulatory structure-property relationship (SPR) and SAR considerations, and for the development of rules for a decision support system (DSS) for the introduction of alternative methods into local irritancy/corrosivity testing strategies. The information stored in the database is derived from proprietary data, so it is not possible to publish the data directly. Therefore, the database is evaluated by regulators, and the information derived from the data is used for the development of scientific information about SARs. This information can be published, for example, by means of tables correlating measured physicochemical values and specific toxic effects caused by the measured chemical. This information is introduced to the public by means of a DSS that predicts local irritant/corrosive potential of a chemical by listing socalled exception rules of the kind IF (physicochemical property) A THEN not (toxic) Effect B and so-called structural rules of the kind IF Substructure A THEN Effect B. These DSS rules “translate” proprietary data into scientific knowledge that can be published.
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Local Irritation/Corrosion Testing Strategies: Development of a Decision Support System for the Introduction of Alternative Methods

Stephan Zinke, Ingrid Gerner, Gabriele Graetschel and Eva Schlede

The notification procedure for new chemicals of the European Union (EU) requires protocols on physicochemical and toxicological tests for the evaluation of physicochemical properties and probable toxic effects of each notified substance. In order to reduce the amount of animal testing, alternative methods should be introduced into toxicity testing. Therefore, we have developed a rule-based decision support system (DSS) for the prediction of the local corrosive/irritant properties of new chemicals. To this end, data on more than 1000 substances were examined, which resulted in approximtely 180 “exception-rules” of the kind IF (physicochemical property) A THEN not (toxic) Effect B. In addition, the structural formulae of the chemicals were analysed, which resulted in approximately 160 “structure-rules” of the kind IF Substructure A THEN Effect B. The DSS can predict (based on theoretical structure-activity relationships) whether a chemical produces: a) corrosive effects (i.e. no testing is necessary; b) might have corrosive effects (i.e. no animal testing, in vitro tests are suitable); and c) will produce no effects or only marginal effects (i.e. animal tests are necessary based on current EU legislation for hazard assessment purposes). In addition, the DSS provides reliable data for legal classification and labelling based on a specific result.
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Testing Wound-healing Activity in T15 Fibroblast Cultures: A Morphometric Analysis

Seval Korkmaz, Hülya Zeytinoglu, Melih Zeytinoglu, Süleyman
Aydin, Yusuf Öztürk, and Hüsnü Can Baser

The purpose was to evaluate the use of mouse T15 fibroblast cell cultures for the investigation of wound-healing activity. In order to investigate their mechanisms of action, the effects of drugs with wound-healing activities were compared by using morphometric analyses by microscopy after cell staining. A number of parameters were used to evaluate the effects of titrated extracts from Centella asiatica and dexpanthenol (drugs that have been used in medical practice for their wound-healing activities) on cultured mouse T15 fibroblasts. These parameters were: the total number of cells; the number of T15 cells in mitosis; the percentages of fusiform, polygonal, round and vacuole-containing cells; and the number of intracellular collagen granules. The results indicate that these two drugs exhibit wound-healing activities by activating fibroblast cells, and have cytoprotective effects, although their mechanisms of action on mouse T15 fibroblasts were different. On the basis of our findings, mouse T15 fibroblast cell cultures seem to be useful for the pharmacological screening of compounds with wound-healing activity.
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Development of a Gill Perfusion Apparatus for Studying the Interaction of Fish Pathogens with Gill Tissue

Annemie Decostere, James F. Turnbull, Richard Ducatelle and Freddy Haesebrouck

An isolated perfused gill preparation was developed for the study of the association of gill pathogens with the branchial tissue. The preparation consisted of an excised branchial arch from common carp (Cyprinus carpio L., minimum weight 300g), perfused via the afferent branchial artery. Filtered and heparinised Cortland solution was used as the perfusion fluid and infused by means of a drip (3-litre bag). The average perfusion rate was 1.5ml/minute/arch/kg body weight. The outflowing perfusate was collected from a cannula in the efferent branchial artery. The individual gill arch was suspended in a circular organ chamber filled with Ringer solution, which was aerated and kept at a constant temperature of 20°C. Unperfused gill arches maintained in Ringer solution at the same temperature served as controls. Cortland solution proved to be a satisfactory perfusion fluid, maintaining the perfused gills in a healthy condition for at least 4 hours with no, or only slight, oedema after 90 minutes, and slight or moderate oedema after 4 hours. The unperfused gill displayed excessive necrosis and loss of architecture after 4 hours. The Cortland perfused gill apparatus could thus prove to be an alternative ex vivo model of particular use in the study of the early interaction of gill associated pathogens with the branchial tissue
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Evaluation of Various Immunisation Procedures in Laying Hens to Induce High Amounts of Specific Egg Yolk Antibodies

Michael H. Erhard, Katja Mahn, Peter Schmidt, Susanne Oltmer,
Rudolf Preisinger, Pia Zinsmeister and Manfred Stangassinger

The present study, involving 972 laying hens divided into 162 groups (n = 6), was aimed at the development of an immunisation protocol for laying hens to produce specific egg yolk antibodies. Recombinant bovine somatotropin (rbst), Escherichia coli pilus antigen K88 (K88), human serum immunoglobulin G (IgG), and low density lipoprotein (LDL) were used as antigens, each at four different doses (rbst, K88, LDL: 1μg, 10μg, 100μg, 1mg; IgG: 0.5μg, 5μg, 50μg, 0.5mg). Three subcutaneous or intramuscular immunisations were performed at intervals of four weeks. The adjuvant used was either the lipopeptide Pam3Cys-Ser-(Lys)4 (PCSL) or Freund’s incomplete adjuvant (FIA), in two different doses (PCSL: 0.1 and 0.25mg; FIA: 0.1 and 0.25ml). In the four antigen control groups, hens were immunised without any adjuvant. In two negative control groups, only physiological saline was injected. The mean egg weight and egg yield were not influenced by the immunisation procedures. An antigen dose of 10–100g per injection was sufficient to induce high specific antibody titres in the egg yolk. The adjuvant efficacy of PCSL and FIA was proved to be the same (p < 0.05 versus antigen control). With PCSL as adjuvant, some groups showed a tendency to produce even higher specific antibody titres than did FIA groups. A second booster often caused a further significant increase in the amounts of specific antibodies, especially with PCSL. Subcutaneous administration of the antigen together with 250μg PCSL, resulted in a significantly higher immune response than when FIA was used.[/fusion_toggle] [/fusion_builder_column][fusion_builder_column row_column_index="1_2" type="1_1" background_position="left top" background_color="" border_size="" border_color="" border_style="solid" spacing="yes" background_image="" background_repeat="no-repeat" padding="" margin_top="0px" margin_bottom="0px" class="" id="" animation_type="" animation_speed="0.3" animation_direction="left" hide_on_mobile="no" center_content="no" min_height="none"][s2If current_user_cannot(access_s2member_level0)] You need to register (for free) to download this article. Please log in/register here.[/s2If]

Endocrine Disruptors: A Critical Review of In Vitro and In Vivo Testing Strategies for Assessing Their Toxic Hazard to Humans

Robert D. Combes

Currently, there is much concern that a wide range of both synthetic and naturally occurring environmental chemicals can act as endocrine disruptors (EDs), and can adversely affect humans and wildlife. Many in vivo and in vitro tests have been proposed for screening EDs, and several regulatory agencies, including the US Environmental Protection Agency (EPA), have recommended tier-testing schemes. Unfortunately, most of the proposed toxicity tests have substantial problems, including non-specificity and lack of reproducibility. There is also uncertainty concerning their relevance for generating useful hazard data for risk assessment purposes, in view of the diversity of the possible ED mechanisms of action (for example, receptor binding, steroidogenesis and modulation of the homeostatic processes which regulate endogenous responses to hormones). Moreover, most of the suggested test methods have yet to be validated according to internationally accepted criteria, although the OECD and the US EPA have defined tests for validation, and an interlaboratory “prevalidation” exercise has been initiated by the OECD. All this is compounded by the lack of information regarding human exposure levels to EDs, and a lack of direct evidence for a causal link between exposure and the development of adverse human health effects. In addition, the regulatory testing of EDs has important negative implications for animal welfare, as some of the proposed in vivo tests require large group sizes of animals and stressful procedures. From a detailed analysis of the available published literature, it is concluded that it is impossible to assess the relative values of currently available in vitro and in vivo toxicity tests for EDs, or to recommend any test or test battery. Any plans for the widespread testing of EDs are therefore premature and might be unnecessary, at least for detecting possible human effects. Several recommendations are made for rectifying this unsatisfactory situation, including the postponement of screening programmes pending: a) more information on human exposure; b) further details of the mechanisms of action of EDs; and c) the development of improved tests, followed by their proper scientific validation.
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Biomarkers as Predictive Tools in Toxicity Testing

Diane J. Benford, A. Bryan Hanley, Krys Bottrill, Sarah Oehlschlager, Michael Balls, Francesco Branca, Jean Jaques Castegnaro, Jaques Descotes, Kari Hemminiki, David Lindsay and Benoit Schilter

This is the report of the fortieth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM’s main goal, as defined in
1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals.
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2017-01-09T06:27:08+00:00 Tags: , |

The Three Rs Declaration of Bologna

ATLA Staff Writer

The “Three Rs” of Russell & Burch, reduction, refinement and replacement, had their origin in a project initiated in 1954 by the Universities Federation for Animal Welfare (UFAW), which led to the publication in 1959 of The Principles of Humane Experimental Technique, by W.M.S. Russell and R.L. Burch (1). In 1978, David Smyth used the word alternatives to define the Three Rs (2).
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2017-01-09T06:27:09+00:00 Tags: |

Book Reviews

Pat Coulson

The aim of this book was to provide an overview of ethics for those who work with animals in a scientific environment. It is divided into three parts, the first of which is a general introduction to ethics. The author begins by defining the term ethics and its related vocabulary. This is followed by a chapter that might be best described as a potted history of ethical theories such as absolutism, relativism, utilitarianism and several more “-isms”.
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2017-01-09T06:27:09+00:00 Tags: |