CAAT Newsletter: Vol. 14, No. 1, Fall 1996

COLIPA Symposium on Alternatives to Animal Testing

By Julia Fentem, Ph.D.

The use of animals in the safety assessment of new cosmetics has probably received the greatest criticism of all types of animal experimentation. Much of the progress made to date with respect to the development and validation of alternative tests has been driven by the requirements of the major cosmetics companies who, to appease their customers, need to be able to manufacture and market new and safe products without undertaking any animal testing. The Sixth Amendment (Directive 93/35/EEC) to the European Union (EU) Cosmetics Directive (76/768/EEC) states that testing on animals of ingredients or combinations of ingredients should be banned as from 1 January 1988, but with the proviso that the proposed ban should be postponed if suitable alternative methods have not been sufficiently validated.

A two-day international scientific symposium organised by the European Cosmetic, Toiletry and Perfumery Association (COLIPA) was held in Brussels on 29-30 November 1995, under the royal patronage of HRH Prince Laurent of Belgium, to review the progress made in developing and validating alternative methods in the context of the cosmetic industry's on-going efforts in this area.

In his plenary lecture on Validation and Safety Assessment, Jacques Leclaire (Head of Life Science Research, L'Oreal, France) gave an excellent overview of the importance and challenges of validation, and of the cosmetic industry's approach to safety assessment. He introduced several points which were also emphasised subsequently by many of the other invited speakers. In particular, Dr. Leclaire outlined the need for cooperation between the cosmetic industry/COLIPA and the European Commission, specifically with DGXXIV and its advisory body, the Scientific Committee on Cosmetology (SCC), and with the European Centre for the Validation of Alternative Methods (ECVAM), with respect to the development, validation and widespread implementation of alternative methods.

The first session, on Validation, was chaired by Fritz Kemper (Professor Emeritus of Pharmacology and Toxicology, Westf. Wilheims-Universitaat, Germany) and included presentations on the concept and challenges of validation, photoirritation, and eye irritation. Bas Blaauboer (Head of Biochemical Toxicology, RITOX, The Netherlands) outlined the basic principles of validation, in the context of reports published in recent years by the European Research Group for Alternatives in Toxicity Testing (ERGATT), ECVAM and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT).

The cosmetic industry's view of validation (as developed by the COLIPA Steering Committee on Alternatives to Animal Testing, SCAAT) and, in particular, the critical role of prediction models, was described by Leon Bruner (Senior Scientist, Procter and Gamble, UK). Dr. Bruner concluded his presentation with a call for better validation of alternatives tests, stating that, at present, the use of alternative methods will not provide the same amount of protection (for the consumer) and that decreased animal use will lead to decreased innovation.

The two presentations on photoirritation were given by Jose Castell (Senior Researcher, University Hospital La Fe, Spain) and Wolfgang Pape (Head of Safety Assessment Centre COSMED, Beiersdorf, Germany). Professor Castell briefly discussed the animal in vitro tests for photoirritation which are currently being used, and outlined the testing strategy proposed by the participants at the ECVAM workshop on phototoxicity. The results of the EU/COLIPA validation study on photoirritation were presented by Dr. Pape.

Rodger Curren (Vice President, Speciality Health and Safety Services, Microbiological Associates Inc., USA) gave an overview of the current situation with respect to eye irritation testing, thereby setting the background for Odile De Silva (Head of External Affairs, Life Science Research, L'Oreal, France) to describe the COLIPA validation study on alternatives to the Draize eye test in the subsequent presentation. A poster on the COLIPA In Vitro eye irritation programme was also on display throughout the symposium. This was the first time that most scientists outside of the cosmetic industry had been afforded the opportunity of seeing the validation approach adopted by COLIPA, and of reviewing the preliminary data which were presented. This complex study, designed to expand upon the EU/ UK Home Office validation study in which only single chemical entities (cf. formulations) were tested, involved assessing the validities of ten in vitro methods.

Central to the study design was the definition of prediction models for each test. Unfortunately, the outcome of the study has been compromised by the failure to include sufficient laboratories for some of the tests; only two laboratories conducted the silicon microphysiometer, tissue equivalent assay (TEA) and fluorscein leakage (FL) methods, precluding proper assessment of the interlaboratory reproducibility of these tests. Determination of interlaboratory reproducibility is considered to be an essential part of any validation study. In addition, the TEA and FL methods were two of the three tests for which the prediction models appeared to be promising.

The Challenge of Validation in Europe was the topic addressed by Michael Balls (Head of ECVAM, Italy) and Mark Chamberlain (Programme Manager for Research, Unilever Research, UK). Professor Balls emphasised the need for all interested organisations and individuals to work together if progress was to be made more quickly, while outlining ECVAM's commitment to both the implementation of alternative tests and testing strategies based on good science, and to improved safety for consumers and manufacturers.

Dr. Chamberlain called for the cosmetic industry to change the way in which it worked. He said that the challenge the industry faced was to find a way to define, in the public domain, the generic rules which currently enable the use of alternative methods for safety evaluation purposes in-house, without compromising confidentiality. In this respect, Dr. Chamberlain emphasised that cosmetics companies must publish to a greater extent in the peer-reviewed literature their approaches and findings, supported by non-confidential data.

The first session concluded with a round-table discussion on regulatory issues chaired by Philip Botham (Head of Regulatory Toxicology ZENECA Central Toxicology Laboratory, UK). The participants were Michael Balls, Frank Baker (Director, Regulatory and Clinical Development, Procter and Gamble, UK), Walter De Klerck (Head of Unit, DGXXIV, European Commission, Belgium), Chris Fisher (Consultant, Eurogroup for Animal Welfare/European Coalition to End Animal Experiments, UK), Maggy Jennings (Head of Research Animals Department, RSPCA, UK), Herman Koeter (Principal Administrator, OECD, France), Yasuo Ohno (Head of Pharmacology Division, National Institute of Health Sciences, Japan), Dagmar Roth-Behrendt (Member of the European Parliament, Germany), and Neil Wilcox (Special Assistant to the Associate Commissioner for Science, FDA, USA).

Each of the participants gave their perspectives on the implications of a potential ban on the animal testing of cosmetics with respect to the validation, acceptance and implementation of alternative methodologies. Not surprisingly, there were some very different opinions expressed by the animal welfare and cosmetic industry representatives. Inhis summary, Dr. Botham emphasised the need for realism in terms of a time-frame for the implementation of alternative methods. He also stated that he felt that the Commission had taken a positive step in establishing ECVAM to coordinate efforts at EU level and thereby facilitate the validation of alternative methods.

The second session, entitled Ongoing Developments, was chaired by Horst Spielmann (Director, ZEBET, BgVV, Germany) and included presentations on percutaneous absorption (Harry Bodde, Associate Professor, Leiden/Amsterdam, Center for Drug Research, The Netherlands; Doug Howes, Manager, Chemical Toxicology Group, Unilever Research, UK), skin compatibility (Ian White, Consultant Dermatologist, St Thomas' Hospital, UK; Walter Matthies, Director of Dermatology, Henkel, Germany) and sensitisation (Conrad Hauser, Head of Allergy Unit, Hopital Cantonal Universitaire de Geneve, Switzerland; Jean-Luc Garrigue, Central Department for Product Safety, L'Oreal, France). The presentation by Dr. Garrigue, on research being conducted as a basis for trying to develop in vitro screens for the detection of potential skin sensitisers, was particularly good.

Frank Baker gave the final presentation of the second session, entitled Industry at the Forefront of Research. He explained that the cosmetic industry's goal was to decrease animal use to the absolute minimum possible, and said that the cosmetic industry was ready to assist the Commission and Member States in meeting their reporting obligations in terms of the requirement of Directive 93/35/EEC relating to the publication of statistics on the number of animals used in cosmetics testing. Dr. Baker then outlined COLIPA's role in organising the cosmetic industry's efforts in the areas of skin compatibility, percutaneous absorption, eye irritation, photoirritation and skin sensitisation testing.

The final session, chaired by Bob Combes (Scientific Director, FRAME, UK), involved discussion of the perspectives of the SCC (Nicola Loprieno, Professor of Genetics, University of Pisa, Italy), the UK (Robin Fielder, Chief Scientific Officer HEF Division, Department of Health and Social Security, UK) and Germany (Eva Schlede, Head of Acute Toxicity Unit, BgVV, Germany) national authorities and industry (Martine Cottin, Deputy Director, L'Oreal, France) on safety assessment. Professor Loprieno mentioned several important initiatives taken by the SCC, in terms of documents and position papers which it had produced on the development and use of alternative methods, and on skin penetration, and in establishing a sub-group on alternatives. He requested that the cosmetic industry provide the SCC with scientific data to support the testing approaches which are now being used in-house. Dr. Fielder clarified the situation with regard to reaching consensus on an acceptable OECD test guideline for in vitro percutaneous absorption studies, an area where there is currently disagreement about the need for using viable skin. This would not appear to be a practical option, or necessary, for routine screening purposes.

In his concluding statements, Frank Fairweather (Chairman, SCAAT) was realistic and positive regarding both the achievements of recent years and possibilities for future progress. He proposed that it was now time to consider a further Three Rs: realism, reassessment and realignment, and called for a strategy to be developed jointly by the cosmetic industry, the SCC, DGXXIV and ECVAM which would make the replacement of animal tests for photoirritation, percutaneous absorption and skin compatibility a real possibility within the next two years.

The presentations given by the invited speakers were complemented by some informative posters which were on display throughout the symposium. These highlighted industry's efforts during the past few years, in particular with regard to the evaluation of alternative methods for eye and skin irritation, photoirritation, percutaneous absorption, skin compatibility and sensitisation testing, and the development of testing strategies to reduce the number of animals used for safety assessment purposes. The full proceedings of the symposium are available from COLIPA (tel: +32 2 227 6610, fax: +32 2 227 6627).

It cannot be disputed that considerable progress has been made in recent years, through the combined efforts of industry and other scientists involved in the development and validation of alternative methods. Nevertheless, there seems to have been a lack of focus, with many related activities being undertaken in parallel and in isolation. If we are to make significant progress as time- and cost-effectively as possible in the future, then it is time to stop the rhetoric about better communication and cooperation, and to actually work together to put these commendable sentiments into practice.