ATLA 26.5, September 1998

//ATLA 26.5, September 1998

Biopharmaceuticals — From Animals or Plants?

Gill Langley

Human insulin and growth hormone, launched commercially in the early 1980s, were among the first therapeutic proteins produced from genetically engineered bacteria and cell cultures. Today, 34 protein-based biopharmaceuticals are on the market, ranging from various interferons, tissue plasminogen activator and erythropoietin, to hepatitis B antigen and blood-clotting factors VIII and IX.
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:26:46+00:00 Tags: |

Non-animal Tests for Evaluating the Toxicity of Solid Xenobiotics

Bice Fubini, Ann E. Aust, Robert E. Bolton, Paul J.A. Borm, Joachim Bruch, Gabriela Ciapetti, Ken Donaldson, Zoé Elias, Julie Gold, Marie Claude Jaurand, Agnes B. Kane, Dominique Lison and
Hartwig Muhle

This is the report of the thirtieth 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. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures.
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:26:46+00:00 Tags: , , |

Progress in Toxicological Testing: Reduction and Refinement Issues

Kim Tichias, Julia Fentem, David Basketter, Philip Botham, Paul Brooker, Leon Bruner, Peter Evans, Steve Fairhurst, Elisabeth Fassold, Robin Fielder, Frank Gerberick, Paul Harvey, Herman Koëter, Paul Parsons, Eva Schlede, David Shannon and Horst Spielmann

This is the report of a meeting organised jointly by the UK Government and the European Centre for the Validation of Alternative Methods (ECVAM), a unit of the European Commission (EC) Joint Research Centre, based at Ispra, Italy.
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:26:46+00:00 Tags: |

Comparative Evaluation of In Vitro and In Vivo Assays for the Detection of Avian Infectious Bronchitis Virus as a Contaminant of Live Poultry Vaccines

Emiliana Falcone, Edoardo Vignolo, Livia Di Trani, Simona Puzelli and Maria Tollis

A reverse transcriptase polymerase chain reaction (RT-PCR) assay specific for identifying avian infectious bronchitis virus (IBV) in poultry vaccines, and the serological response to IBV induced by the inoculation of chicks with a Newcastle disease vaccine spiked with the Massachusetts strain of IBV, were compared for their ability to detect IBV as a contaminant of avian vaccines. The sensitivity of the IBV-RT-PCR assay provided results which were at least equivalent to the biological effect produced by the inoculation of chicks, allowing this assay to be considered a valid alternative to animal testing in the quality control of avian immunologicals. This procedure can easily be adapted to detect a number of co
You need to register (for free) to download this article. Please log in/register here.

A Germination Bioassay as a Toxicological Screening System for Studying the Effects of Potential Prodrugs of Naproxen

Mario Gonzalez-de la Parra, Carlos Ramos-Mundo, Manuel Jimenez-Estrada, Claudia Ponce-de Leon, R. Castillo, Veronica Tejeda, Karla G. Cuevas and Raul G. Enriquez

A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β−2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+)-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-β−methyl-2-naphthaleneethyl 6-methoxy-α−methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus.
You need to register (for free) to download this article. Please log in/register here.

Alternative Approaches and Tests in Ecotoxicology: A Review of the Present Position and the Prospects for Change, Taking into Account ECVAM’s Duties, Topic Selection and Test Criteria

Colin H. Walker

The objectives of this review are to summarise the present position concerning the use of vertebrates in ecotoxicity testing, giving particular attention to tests that cause suffering, and to discuss in some detail, alternatives to them, and the prospects for change. The report has been written with the objectives of the European Centre for the Validation of Alternative Methods (ECVAM) in mind, and some recommendations for action have been made at the end of the discussion section. The first section of the review describes the present requirements within the European Union for the ecotoxicity testing of industrial chemicals in general, and for pesticides in particular, and the very limited documentation of the tests that are actually carried out. The next four sections describe the many different assays and systems used to evaluate the harmful effects of chemicals on free-living organisms and natural populations, and the extent to which they might be suitable alternatives to vertebrate toxicity tests that cause suffering. Attention is drawn to certain assays and strategies that can already be used as satisfactory alternatives, and thus provide the basis for short-term change. Included here are nondestructive assays on vertebrates which are available for certain types of chemicals, and which provide a direct and relatively uncomplicated approach to the problem. Other approaches are described which still require development, but hold considerable promise in the longer term. The growth of knowledge in the broad field of biochemical toxicology and the development of related technologies should lead to the development of better and more-sophisticated alternatives in the future. In vitro assays employing vertebrate cell systems are of particular interest here. The last section of the review deals with conclusions and recommendations. The recommendations are made with a view to the activities and responsibilities of ECVAM.
You need to register (for free) to download this article. Please log in/register here.

A Study on UV Filter Chemicals from Annex VII of European Union Directive 76/768/EEC, in the In Vitro 3T3 NRU Phototoxicity Test

Horst Spielmann, Michael Balls, Jack Dupuis, Wolfgang J. W. Pape, Odile de Silva, Hermann-Georg Holzhütter, Frank Gerberick, Manfred Liebsch, Will W. Lovell and Uwe Pfannenbecker

In 1996, the Scientific Committee on Cosmetology of DGXXIV of the European Commission asked the European Centre for the Validation of Alternative Methods to test eight UV filter chemicals from the 1995 edition of Annex VII of Directive 76/768/EEC in a blind trial in the in vitro 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) test, which had been scientifically validated between 1992 and 1996. Since all the UV filter chemicals on the positive list of EU Directive 76/768/EEC have been shown not to be phototoxic in vivo in humans under use conditions, only negative effects would be expected in the 3T3 NRU PT test. To balance the number of positive and negative chemicals, ten phototoxic and ten non-phototoxic chemicals were tested under blind conditions in four laboratories. Moreover, to assess the optimum concentration range for testing, information was provided on appropriate solvents and on the solubility of the coded chemicals. In this study, the phototoxic potential of test chemicals was evaluated in a prediction model in which either the Photoirritation Factor (PIF) or the Mean Photo Effect (MPE) were determined. The results obtained with both PIF and MPE were highly reproducible in the four laboratories, and the correlation between in vitro and in vivo data was almost perfect. All the phototoxic test chemicals provided a positive result at concentrations of 1µg/ml, while nine of the ten non-phototoxic chemicals gave clear negative results, even at the highest test concentrations. One of the UV filter chemicals gave positive results in three of the four laboratories only at concentrations greater than 100µg/ml; the other laboratory correctly identified all 20 of the test chemicals. An analysis of the impact that exposure concentrations had on the performance of the test revealed that the optimum concentration range in the 3T3 NRU PT test for determining the phototoxic potential of chemicals is between 0.1µg/ml and 10µg/ml, and that false positive results can be obtained at concentrations greater than 100µg/ml. Therefore, the positive results obtained with some of the UV filter chemicals only at concentrations greater than 100µg/ml do not indicate a phototoxic potential in vivo. When this information was taken into account during calculation of the overall predictivity of the 3T3 NRU PT test in the present study, an almost perfect correlation of in vitro versus in vivo results was obtained (between 95% and 100%), when either PIF or MPE were used to predict the phototoxic potential. The management team and participants therefore conclude that the 3T3 NRU PT test is a valid test for correctly assessing the phototoxic potential of UV filter chemicals, if the defined concentration limits are taken into account.
You need to register (for free) to download this article. Please log in/register here.

Letter from CAAT

Lisa A. Libowitz

For anyone interested in the third of the Three Rs — refinement — Washington, DC, USA is the place to be this November, for a special workshop on pain and distress in laboratory animals.
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:26:47+00:00 Tags: |