ATLA 37.4, September 2009

//ATLA 37.4, September 2009

News & Views

ATLA Staff Writer

FRAME at the 7th World Congress
Patrons of Animal Welfare in the Life Sciences
Concern Over Further Increase in Laboratory Animal Use in the UK
New Genes from Non-coding DNA
REACH Legislation May Require More Animals and Funds than Previously Estimated
New Altweb Website Launched
Publication of the Alternative Testing Strategies Progress Report 2009 — Genomics and Biotechnology for Health
Development of a Human Brain Model
Biological Warfare in Bacteria Offers Hope for New Antibiotics
Daylight Could Help Weight Control
Dieter Lütticken Award 2008
Video of EpiDerm Skin Irritation Test (SIT) Method Now Available
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2017-01-09T06:37:46+00:00 Tags: |

IIVS News & Views

ATLA Staff Writer

Alternatives Highlights — the First Half of 2009
Practical Methods for In Vitro Toxicology Workshop 2009
BCOP and ICE Test Guidelines
SCCS Position Statement
Meeting Report — Forinvitox: From Innovation to Market Success
OECD Draft Guideline for Skin Irritation
EFSA Presents Strategy to Reduce Animal Testing
Recent IIVS Presentations
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Can Drug Safety be Predicted and Animal Experiments Reduced by Using Isolated Mitochondrial Fractions?

Susana P. Pereira, Gonçalo C. Pereira, António J. Moreno and Paulo J. Oliveira

Mitochondrial toxicity has resulted in the withdrawal of several drugs from the market. One particular example is nefazodone, an anti-depressant withdrawn in the USA due to hepatoxicity caused by drug-induced mitochondrial dysfunction. Drug development and safety testing can involve the use of large numbers of laboratory animals, which, without a decisive pre-screening for mitochondrial toxicity, are often unable to pre-empt higher mortality rates in some patient groups. The use of isolated mitochondria as a screening tool for drug safety can decrease the number of laboratory animals used in pre-clinical studies, thus improving animal welfare and healthcare outcomes and costs. Novel techniques involving highthroughput methods can be used to investigate whether a molecule is a mitochondrial toxicant. Moreover, these screens are mechanistically-based, since the effects of the drug on oxidative phosphorylation, calcium homeostasis and mitochondrial genetics can be assessed. This review is intended to demonstrate that isolated mitochondrial fractions are suitable for predicting drug and general chemical safety in toxicological screenings, thus contributing to the refinement and reduction of animal use in laboratory research.
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Twenty-first Century Challenges for In Vitro Neurotoxicity

Robert A. Smith

During the last 40 years, studies incorporating in vitro methodologies have greatly advanced our understanding of human nerve cell biology. Attempts have been made to apply these to investigations of neurotoxicity. Due to the complexity of the nervous system, underpinned by an array of integrated interactions between a host of cell types, it is concluded that, at present, alternative neural models are most successful in determining the underlying mechanisms which can cause perturbation of normal functioning of the nervous system, both in adults and during the embryonic period. The use of tiered batteries of test models has been proposed in screening programmes for neurotoxicity, with the generation of much encouraging data in laboratories across the globe. This review aims to discuss the development of neural alternatives, considers the various model systems available, and highlights specific neuronal endpoints which can be tested, in addition to the cytotoxic evaluation of neuronal viability. Developments in molecular and stem cell biology, which are appropriate to neural tissue, and which offer the prospect of exciting advances for the next decade, are cited.
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The Use of the Integrated Discrete Multiple Organ Coculture (IdMOC®) System for the Evaluation of Multiple Organ Toxicity

Albert P. Li

The application of the Integrated Discrete Multiple Organ Co-culture (IdMOC®) system in the evaluation of organ-specific toxicity is reviewed. In vitro approaches to predict in vivo toxicity have met with limited success, mainly because of the complexity of in vivo toxic responses. In vivo properties that are not well-represented in vitro include organ-specific responses, multiple organ metabolism, and multiple organ interactions. The IdMOC system has been developed to address these deficiencies. The system uses a ‘wells-within-a-well’ concept for the co-culturing of cells or tissue slices from different organs as physically separated (discrete) entities in the small inner wells. These inner wells are nevertheless interconnected (integrated) by overlying culture medium in the large outer containing well. The IdMOC system thereby models the in vivo situation, in which multiple organs are physically separated but interconnected by the systemic circulation, permitting multiple organ interactions. The IdMOC system, with either cells or tissue slices from multiple organs, can be used to evaluate cell type-specific or organ-specific toxicity.
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Immunotoxicology: Opportunities for Non-animal Test Development

Emanuela Corsini and Erwin L. Roggen

At present, several animal-based assays are used to assess immunotoxic effects such as immunosuppression and sensitisation. The use of whole animals, however, presents several secondary issues, including expense, ethical concerns and relevance to human risk assessment. There is a growing belief that non-animal approaches can eliminate these issues without impairing human safety, provided that biological markers are available to identify the immunotoxic potentials of new chemicals to which humans may be exposed. Driven by the 7th Amendment to the EU Cosmetics Directive, the new EU policy on chemicals (the REACH system), proposals to update the European legislation on the protection of animals used in research, and emerging visions and strategies for predicting toxicity, such in vitro methods are likely to play a major role in the near future. The realisation that the immune system can be the target of many chemicals, resulting in a range of adverse effects on the host’s health, has raised serious concerns from the public and within the regulatory agencies. Hypersensitivity and immunosuppression are considered the primary focus for developing in vitro methods in immunotoxicology. However, in vitro assays to detect immunostimulation and autoimmunity are also needed. This review of the state-of-the-art in the field of in vitro immunotoxicity, reveals a lack of cell-based immunotoxicity assays for predicting the toxicity of xenobiotics toward the immune system in a simple, fast, economical and reliable way.
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An Examination of Chimpanzee Use in Human Cancer Research

Jarrod Bailey

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human genomic studies. Papers describing potential new cancer therapies noted significant concerns regarding the chimpanzee model. Other studies described interventions that have not been pursued clinically. Finally, available evidence indicates that chimpanzees are not essential in the development of therapeutic monoclonal antibodies. It would therefore be unscientific to claim that chimpanzees are vital to cancer research. On the contrary, it is reasonable to conclude that cancer research would not suffer, if the use of chimpanzees for this purpose were prohibited in the US. Genetic differences between humans and chimpanzees, make them an unsuitable model for cancer, as well as other human diseases.
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