ATLA 27, 1999

/ATLA 27, 1999

The Use of Human Keratinocytes in the EU/COLIPA International In Vitro Phototoxicity Test Validation Study and the ECVAM/COLIPA Study on UV Filter Chemicals

Richard Clothier, Angie Willshaw, Helen Cox, Michael Garle, Helen Bowler and Robert Combes

The EU/COLIPA in vitro phototoxicity study involved the testing of 30 chemicals in Phase II, and the ECVAM/COLIPA study on UV filter chemicals involved the testing of 20 chemicals, for which in vivo human and/or animal data were available. Primary human keratinocytes, from four separate male donors, were not found to be sensitive to the 5J/cm2 UVA produced by the SOL500 lamp when assayed by using the neutral red uptake endpoint, as employed with the 3T3 cells used in these international interlaboratory validation studies. The primary human keratinocytes tested in one laboratory alongside the 3T3 fibroblasts gave consistent indications of phototoxicity with all the phototoxicants tested in the Phase II and UV filter studies. The one exception was bithionol, which was predicted to be non-phototoxic in both studies. None of the non-phototoxic chemicals resulted in a positive reaction with the Photoirritation Factor (PIF) version of the prediction model. However, when the Mean Photo Effect (MPE) prediction model version was applied (with a cut-off point of 0.1), one sunscreen agent, octyl salicylate, was deemed to have phototoxic potential. The entire set of negative rated chemicals included in Phase II and in the UV filter study were also rated as non-phototoxic by the MPE prediction model.
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Selective Induction of Interleukin-12 in Reconstructed Human Epidermis by Chemical Allergens

Emanuela Corsini, Elena Limiroli, Marina Marinovich, Catherine
Cohen, Roland Roguet and Corrado L. Galli

Keratinocytes play an important role in skin inflammatory and immunological reactions through the release of cytokines and response to them. These cells have been shown to direct T-cell priming by producing cytokines such as interleukin (IL)-10 and IL-12. The purpose of this work was to explore the potential use of IL-12 production to discriminate between skin irritants and contact allergens in vitro. Initially, a reconstituted human epidermis was treated with a known human skin irritant, sodium lauryl sulphate (SLS), and a known human contact allergen, 1-chloro-2,4-dinitrobenzene (DNCB). The expression of IL-12p40 was assessed at specific time intervals by the semi-quantitative reverse transcriptase-polymerase chain reaction (rt-PCR). The data obtained indicated that only DNCB induced an up-regulation of IL-12p40. This up-regulation occurred after exposure to DNCB for 3 hours. Importantly, the application of SLS or vehicles did not induce IL-12 mRNA up-regulation. An increase in total IL-12 protein content was detected in supernatants of allergen-stimulated, but not vehicle-stimulated, reconstituted epidermis. To confirm these results, the effects of benzalkonium chloride, oxazolone and eugenol were assessed. At concentrations that resulted in equivalent IL-1α release, only contact allergens increased IL-12 expression, which confirmed the previous results. These data suggest that IL-12, which is crucial for T-helper type 1 cell responses, could be a useful marker for discriminating between contact allergens and irritants.
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Alternative Methods for Assessing Biocompatibility and Function of Implant Materials

Malgorzata Lewandowska-Szumiel

Biocompatibility testing is used to evaluate the host response to implantable materials and to assess their ability to perform in applications in which they are intended to interact with biological systems. In compliance with international and/or national standards, such assessment is based mainly on the results of experimental implantation into animal tissues. However, the development of in vitro experimental techniques creates new opportunities to observe and to understand the interaction of biomaterials with host tissue. The state-of-theart application of alternative methods in biocompatibility testing is presented in this review article. It is discussed with respect to the Three Rs concept (reduction, refinement, replacement) of Russell & Burch. Perspectives on alternative methods in biocompatibility studies are discussed with regard to the possible role of biomaterials in tissue engineering.
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Lack of Effect of Medium Supplementation With Pyruvate and Hormones on Cytochrome P450-mediated Activity of Rat Hepatocytes in Primary Culture

Porntip Wirachwong and Jeffrey R. Fry

The loss of cytochrome P450 (CYP)-dependent activity continues to be a problem in the use of cultured hepatocytes in xenobiotic toxicity studies. It has been reported that the inclusion of pyruvate and various hormones in the culture medium improves the maintenance of various hepatic functions, including that of CYP2C11 mRNA expression. We have studied this further, by investigating the effects of the addition of pyruvate and hormones on various CYP-dependent enzyme activities and on the CYP-dependent toxicity of precocene II in rat hepatocyte cultures. No beneficial effects of this medium supplementation could be demonstrated.
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Letter from CAAT

Lisa A. Libowitz

Animal Testing (CAAT) is coordinating an initiative to examine the current status of alternative methods for Screening Information Data Sets (SIDS) endpoints, and to make recommendations about the use of these methods in the High Production Volume (HPV) Challenge Program. This effort, dubbed “TestSmart”, began with funding provided by a Heinz Foundation grant awarded to the Environmental Defense Fund (EDF), the University of Pittsburgh, Carnegie-Mellon University, and CAAT.
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2017-01-09T06:26:55+00:00 Tags: |

Conference Reports

ATLA Staff Writer

This meeting, held in Vienna on 16–17 November 1998, was organised by the Austrian Federal Ministry of Science and Transport, during the Austrian Government’s first Presidency of the European Union (EU). Animal testing represents a sensitive issue throughout the EU, and culture and animal protection are inseparably linked. The level of responsible treatment of animals within research in general, and during animal testing in particular, reflects the degree of humanity within society.
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2017-01-09T06:26:55+00:00 Tags: |

Book Review

David Morton

This book aims to provide basic information on the anatomy, physiology, genetics, behaviour, husbandry, common techniques, anaesthesia, postoperative care, common disease profile, therapeutics and humane methods of killing of several commonly used laboratory animals (mice, rats, gerbils, hamsters, guinea-pigs, chinchillas, rabbits, ferrets and non-human primates). It is a well referenced book, from a laboratory animal science point of view, and gives valuable guidance on technical aspects, making it potentially very useful. There is also a section on US law concerning the care and use of laboratory animals, and tables provide some haematological and biochemical data.
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2017-01-09T06:26:56+00:00 Tags: |

New Measures on Animal Experimentation in the UK Will Improve Animal Welfare and Scientific Research

Robert D. Combes

On reading the lead article, The Increasing Burden of Regulation, in the April 1999 issue of RDS News,1 I experienced a mixture of emotional states, ranging from disbelief and annoyance to frustration and sadness. In this article, the Executive Director of the Research Defence Society, Mark Matfield, claims that the new measures introduced by the Labour Government to the existing legislation controlling animal experimentation in the UK will improve animal welfare but hinder scientific research. Dr Matfield asserts that the degree of regulation now facing investigators “is seriously impeding some areas of science in the UK”. He believes that the increased focus on animal welfare is not justified in terms of the likely resulting loss of scientific benefits.
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2017-01-09T06:26:56+00:00 Tags: |