ATLA 26, 1998

/ATLA 26, 1998

The Production of Genetically Modified Animals and Humans: An Inescapable Moral Challenge to Scientists and Laypeople Alike

Michael Balls

This issue of ATLA contains the report of an ECVAM workshop on the use of transgenic animals. 1 It is a courageous attempt to consider all aspects of the potential benefits, welfare implications and ethical dilemmas inherent in one of the fastest growing areas of biomedical research — the modification of animals by the artificial introduction of genetic material into their germlines.
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Issues Relating to the Release of Proprietary Information and Data for Use in the Validation of Alternative Methods

Martin Todd, Bernward Garthoff, Wilfried Bernhardt, Gerd Bodé, Spencer Farr, Roman Kolar, Cyndy Lumley, Moniek Pieters, Vera Rogiers, Ursula Sauer, Horst Spielmann, Joseph Straus and Lars Warngard

This is the report of the twenty-seventh 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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The Use of Transgenic Animals in the European Union

T. Ben Mepham, Robert D. Combes, Michael Balls, Ottavia Barbieri, Harry J. Blokhuis, Patrizia Costa, Robert E. Crilly, Tjard de Cock Buning, Véronique C. Delpire, Michael J. O’Hare, Louis-Marie Houdebine, Coen F. van Kreijl, Miriam van der Meer, Christoph A. Reinhardt, Eckhard Wolf and Anne-Marie van Zeller

This is the report of the twenty-eighth 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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A Quantitative Structure-toxicokinetic Relationship Model for Highly Metabolised Chemicals

Patrick Poulin and Kannan Krishnan

The aim of the present study was to develop a quantitative structure-toxicokinetic relationship (QSTkR) model for highly metabolised chemicals (HMCs). The proposed QSTkR model is essentially a physiologically based toxicokinetic (PBTK) model, in which the blood:air and tissue:blood partition coefficients (PCs) are predicted from the molecular structure of chemicals, and the liver blood flow rate (Ql) is used to describe hepatic clearance. Molecular structure-based prediction of the blood:air and tissue:blood PCs was performed from the n-octanol:water and water:air PCs of chemicals obtained with the conventional fragment constant methods. The validity of incorporating Ql instead of metabolic rate constants, as the hepatic clearance factor, in PBTK models for HMCs (extraction ratio > 0.7) was verified by comparing the simulations of venous blood concentration (Cv) profiles obtained with both the QSTkR and PBTK model approaches for 1,1-dichloroethylene, trichloroethylene and furan in the rat. Following the validation of this alternative approach for describing hepatic clearance of HMCs, a QSTkR model for dichloromethane was constructed. This model used molecular structure information as the sole input, and provided simulations of Cv for human exposure to low concentrations of dichloromethane. The QSTkR model simulations were similar to those obtained with the previously validated, conventional human PBTK model with experimentally determined PCs and metabolic rate constants (Vmax, Km and Kf) for dichloromethane. The present methodology is the first validated example of a mechanistically based prediction of the inhalation toxicokinetics of HMCs made solely from information on molecular structure.
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The Neutral Red Uptake Assay: Comments on the Results of the Istituto Superiore di Sanità in the EC/HO Validation Study

Annalaura Stammati, Franco Zampaglioni and Cristiana Zanetti

The neutral red uptake (NRU) assay was included, among others, in a validation study sponsored by the European Commission/British Home Office (EC/HO) study, for its reliability as an in vitro alternative to the Draize eye irritancy test. The test was performed in parallel by four laboratories (Istituto Superiore di Sanità [ISS], Microbiological Associates, Hatano
Research Institute and Kurabo Industries) on 60 selected chemicals. The results obtained by the ISS are reported in this paper. A poor rank correlation was obtained between the in vivo endpoint and the ISS in vitro results for the full set of chemicals and for the subsets, with the exception of surfactants, by an independent statistics group. The same unsatisfactory results were obtained by the ISS group when the rank correlation was calculated for compounds divided into chemical groups. The performance of the NRU assay, as an alternative to the Draize eye irritancy test, is discussed.
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Letter from the NCA

Jan van der Valk

Recently, I received the Masters thesis of Carlo Jochems on the “Use, Trade and Harvest of Livestock Sera”. In his report, Jochems describes the harvesting, trade and use of fetal bovine serum (FBS), also often expressed as fetal calf serum (FCS).
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Conference Reports

Caren Broadhead and Anne-Marie van Zeller

In 1995, the Animal Procedures Committee (APC) reported its considerations on the means by which local ethical review processes (ERPs) could be improved. It reviewed a variety of published material, the most relevant being reports by the Boyd Group and the RSPCA. In response to the APC report, the Home Office invited Certificate Holders to consider whether their establishment would benefit from the implementation of one or other of a variety of ERPs described.
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