Day 1, October 27, 2001
Moderator: Prof. V. Rogiers
Prof. Rogiers welcomed the participants on behalf of the ecopa working group members to the second ecopa workshop on alternative methods and gave a brief introduction to the programme and objectives of the forthcoming two-day meeting.
The intention was to establish ecopa as a EuropeaMon Consensus Platform that would bring all national consensus platforms together, in which the four concerned parties are represented, that is animal welfare, academia, industry and government institutions. The idea was first brought up at the Bologna workshop on alternative methods in 1999, which then lead to the first ecopa workshop, held in Brussels in 2000 where the idea for establishing a European Consensus Platform for Alternative Methods was discussed.
By now, 10 national consensus platforms were fit and willing to join compared to the three that had at first expressed their interest. The time had now come to establish ecopa finally. Yet, it was also made clear by the national consensus platforms that ecopa shall not be a mere association but one that makes a distinct difference with working groups specialising in 3R-matters in order to get alternative methods implemented. It was also stressed that the working basis has to be the 3R’s concept (refinement, reduction, replacement) with particular but not the sole emphasis on replacement.
The New EU Chemicals Policy had been chosen as this year’s main topic since it is a current and really critical issue with respect to animal welfare and the use of alternative methods instead of animal experiments.
Furthermore, gratitude was expressed to the sponsors whose contributions were crucial in the realisation of this year’s workshop, namely the Doerenkamp-Zbinden-Foundation (CH), ZorgOnderzoek Nederland (NL), the Belgian Ministry for Consumer Protection, Public Health and Environment as, the German Federal Ministry of Education and Research as well as the 3R Research Foundation (CH) and the Swedish Fund for Research without Animal Experiments.
Opening: Mrs. M. Aelvoet, Belgian Minister for Consumer Protection, Public Health and Environment
Mrs. Aelvoet expressed her pleasure to take part in the foundation of ecopa since the effective use of alternative methods, the implementation of the 3R’s strategy and animal welfare in Belgium all fall under her responsibility. She personally supports the idea of ecopa, an independent non-governmental organisation, playing a crucial role in the development, promotion and application of alternative methods to the use of experimental animals in research and regulatory testing. As the ecopa strategy is based on a European consensus between the different parties involved, she can fully support this initiative. Moreover, she felt that the founding of such a non-governmental organisation comes at the right time at the right place.
Mrs. Aelvoet saw several areas where ecopa could be of great importance. First of all ecopa could play a major role in assisting to develop expert opinions and recommendations concerning alternative methods and strategies.
A further role was seen for ecopa in its bridging capacity towards the European Parliament. With respect to strengthening this capacity even further she recommended to enlarge the group of national platforms representatives by renowned expert members of other groups with interest in animal welfare and the issues around alternative methods, such as recognised scientists, opinion leaders etc. She felt that the European Parliament as much as herself would be prepared to consider the recommendations made by such a balanced group, backed up by sound science, rather than to listen to individual opinions and biased advice.
Furthermore, she added that an additional major task for ecopa would be in diffusing the vast amount of information on alternative methods throughout the EU. This could be achieved by the individual efforts of the different representatives of the national platforms. Also, picking up new alternative methods in the different member states and bringing these to the attention of local authorities and EU bodies, would be an achievable and desirable objective.
Finally, she stressed that a further important task could be to support the research on alternative methods initiated by the Commission. Since national platforms usually support local research on alternative methods, it would make sense to bundle such efforts and to direct them towards a common goal across Europe.
By summing up the current priorities in animal welfare where ecopa could contribute with expert opinions, bridging efforts, information diffusion and research, she also referred to the threats in conjunction with animal health in intensive farming, the improvement of conditions of long-distance transport of live animals and a workable solution for the integration of the 3R’strategy into safety testing for cosmetics. Major priorities are the new EU Chemicals Policy and finally the research and necessary funding for developing and validating alternative methods.
Closing, Mrs. Aelvoet renewed her support for the initiative and expressed her eagerness to help ecopa in getting a good start. She would therefore try to make it possible that ecopa is invited as an interested party in key meetings with respect to alternative methods and related research issues, the 6th framework programme as well as proposals for 3R’s testing in the international frame.
Dr. J. Vogelgesang: The White Book Strategy for a Future Chemical Policy: Intentions of the Commission
Giving a short overview in regard to the key objectives given in the White Paper that are sustainable development, comprising economic, ecological and social elements, the important issues addressed in the White Book are the protection of health and environment, the innovation and competitiveness of the EU chemical industry, the prevention of fragmentation of the Internal Market, increased transparency, the integration with international efforts and the promotion of non-animal testing.
The promotion of non-animal testing in this regard means that there shall be as minimal animal testing as possible. The key message is therefore that the EU Chemicals Policy is not a testing programme. The intention of the White Paper is not to run a large testing scheme but to gather the necessary information about chemicals that may be readily available with industry, authorities and so on. Only in those cases where sufficient data is not available to assess the risks then testing will be required and evidently one would try the best to use as few animals as possible.
One of the guiding principles in the White Paper was precaution meaning that it is better to look beforehand into the dangerous properties of a chemical so that later the risk can be managed much better. In practice fixing the damages caused by chemicals were normally much more expensive than looking into the dangers and managing the risks properly beforehand. Substitution is another guiding principle of the White Paper.
Giving background information on the initialisation of the White Paper, Dr. Vogelgesang referred to the issue of “existing” and “new” chemicals in the current EU chemicals policy. He outlined that there are about 2800 of such new chemical substances, all of them are basically tested and about 70 per cent are known to be dangerous.
He stressed the need to know the intrinsic dangers properties of chemicals and exposure since only then it would be possible to do the proper risk assessment. It would not be enough to just look at the production volume, the exposure or the use of chemicals as a basis. Only when the risks and dangers are clear, then the respective legislation can be efficient in protecting people from the risks of chemicals.
According to data from the European Chemicals Bureau (ECB), Dr. Vogelgesang pointed out that there is no data available on about 15 per cent of the high production volume chemicals. So, even if there were in practice some data here and there available, it would not be possible to assess the risks of these chemicals, perhaps not even with respect to their acute toxicity.
There is legislation in place but it would not suffice to protect people. The existing problems were that existing substances could be used more or less without testing. Secondly, public authorities would have to prove why a certain chemical was too dangerous. Thirdly, that there was no efficient instrument to ensure the safe use of the most problematic substances and finally, there was also a lack of incentives for innovation, in particular of less hazardous substitutes.
The REACH-System in contrast would provide for a single, coherent system for new and existing chemicals with three elements (Registration, Evaluation and Authorization of CHemicals), thus providing a tiered approach with focus on chemicals in high volumes or of great concern.
There is a registration foreseen for all chemicals being produced which includes a dossier containing such elements as information on its identity and properties, its uses, the envisaged production volume, the labelling, a classification data sheet and a preliminary risk assessment. It is believed that such data will be sufficient for approximately 80 per cent of the chemicals presently on the market.
Regarding chemicals of 1 to 10 tons production volume per year, the White Paper foresees that only in vitro testing should be carried out. The problem at hand was to determine the type of required information and to gather the existing in vitro methods. People argue that there were currently not enough in vitro methods available. Dr. Vogelgesang stressed the importance of not losing time to speed up efforts to develop additional alternative methods.
Concerning chemicals of 100 tons and more or lower giving reasons for concern, evaluation applies as a second step. Authorities will take a much closer look at the data contained in the dossier prior to production or importation. Authorization affects those chemicals with CMR (categories 1 and 2) and POP’s relevance. The idea here is that these chemicals are only produced, marketed or imported once an authorization is granted prior to the producer or importer providing data via a risk assessment that the use of a this substance is safe.
An estimated 2600 substances of high production volume (over 1000 t) shall be registered until 2005, another 2900 substances (100 – 1000 t) until 2008 and finally the rest (20.000 of 1-10 t and 4600 of 10-100 t) until 2012. Modulations could be provided for substances recognised as being of priority, such as CMR (categories 1and 2) substances, where registration might be requested by 2005.
Regarding the benefits of the REACH-Model, Dr. Vogelgesang summarised that it would lead to equal levels of protection as well as equal competitive advantages for new and existing substances. The testing requirements for new substances would be increased to 1 ton to improve innovation but without a significant loss of protection. There would also be equal advantages for producers and importers of products containing hazardous substances. Furthermore, the testing requirements between 1 and 10 tons would generally be limited to in-vitro testing thereby saving animals’ lives.
Dr. Vogelgesang mentioned that the Commission had established a task force comprising 8 working groups to deal with the technical issues. The working group meetings are scheduled to last until February 2002 and further meetings could be held afterwards in order to elaborate guidance documents, where needed. Invited experts from member states, industry, and trade unions as well as green and animal welfare NGOs were supporting them.
He concluded that the benefits of the New Chemicals Policy would be a high level of protection, an improved knowledge, a better tracking of chemicals, a better use of resources, a better reaction to sudden risks, a substitution of most dangerous substances, and it would also encourage innovation and enable better informed choices.
Asked by Dr. Kayser, if the new chemical policy after all wasn’t triggering a lot of additional animal testing, Dr. Vogelgesang replied that it was currently not possible to say how much testing would actually be needed. If there was really all that data available that industry claimed to have then there would probably not be that much testing necessary. But at the present stage that was pure speculation since one could not say for sure whether that data was indeed available.
When asked, if testing requirements should not be reduced in such cases where chemicals would not have any exposure to the environment but only be handled in industry, Dr. Vogelgesang agreed in principle provided that such chemicals are used in a closed system with vigorous containment guaranteed.
Dr. Weber inquired about the state of the art regarding first step exposure models and their acceptance in the EU; Dr. Vogelgesang referred to Dr. Vollmer of the ECB as the expert and asked him to reply. Dr. Vollmer pointed out that such exposure models were elaborated five years ago, that they have been updated just recently and that they are in use.
Dr. B. Garthoff: The European White Book on Chemicals: Start into an Area of Alternatives to Animal Experimentation?
Dr. Garthoff started out by looking at the White Paper in comparison to the 6th Framework Programme that were both released in early 2001. It would have been a perfect opportunity to get both connected in terms of providing funding for the development of those in-vitro methods in the 6th Framework Programme that are lacking to reach the objectives as outlined in the White Paper. Yet, it was not done and the draft version of the 6th Framework Programme did not include any key provision for the funding of alternative methods. When the ecopa working group got knowledge of the draft, the members decided that this was definitely an issue that urgently needed to be addressed publicly, even though ecopa was not officially founded yet.
The working group had therefore prepared a statement that was sent to the Commission and the European Parliament pointing out that no provision was included in the programme and that there was even no mentioning of alternative methods in other key actions. The ecopa-working group therefore called in its statement on the Commission to revise the draft Framework Program in order to include the development of alternative methods as one of its priorities.
Philippe Busquin, Member of the Commission, responded to the statement in which he expressed his gratefulness for the interest that ecopa had demonstrated in the future European research. He responded that the new Framework Programme included several general statements regarding the respect of animal welfare, which concerned all activities of the new Framework Programme, explicitly referring to a footnote on page 18 of the text. This footnote, however, only reads that “as far as possible, animal experiments and testing should be replaced by in vitro or alternative methods. Animal suffering must be avoided or kept to a minimum…”.
Giving examples and quoting representatives of various organisations, Dr. Garthoff continued that the interests of the stakeholders concerned differed and were not necessarily all focused on the issue of testing in the first place. There were different views among the member states of which Sweden saw the need for a fundamental change in the chemicals policy while other countries expressed their concern for the competitiveness of their own chemical industry. Other stakeholders such as animal welfare organisations would focus on the availability of alternative methods and question the need for testing altogether while environmental groups emphasised the need for adequate data to protect the environment and human health. The trade unions were concerned about social aspects while the chemical industry first regarded the whole issue as a nuisance that one needed to get done and over with. Scientists on the one hand were worried about sound science being overridden in favour of political bias while the Commission on the other hand thought that the problem of additional animal experiments was blown out of proportion.
Yet, Dr. Garthoff acknowledged that the White Paper contained a kind of “vision” in regard to alternatives to animal experiments in several places such as the “promotion of non-animal testing” under 2.2 or the “development of alternative methods” under 3.2. But he also emphasised that there was no information on expenses for method development was given in the costs and benefits section.
The White Paper gives no estimate regarding the number of animals that would have to be used. There is only an estimate with respect to the number of substances to be evaluated ranging from 22.500 up to 30.000 that would cost approximately 2.1 billion Euro over an 11 year time period. Other sources, however, suggest that the number of animals used could total 9.6 million or even reach 12.8 million if all 30.000 substances were tested. The total costs could run between 8.0 and 8.68 billion Euro.
Another “vision” to be disputed, was the assumption by Michael Balls (ECVAM) made at the Brussels Stakeholders Conference that “with political and scientific will, it would only take 5 years to validate many alternative methods to lab animal procedures for a variety of effects”. Dr. Garthoff contested here that reality up to this day had proven the opposite. It took several years, respective decades (taking the introduction of HET CAM test a starting point) of developing and validating alternatives to the rabbit eye DRAIZE test, ending with none up to now.
His personal “vision” was that the Commission would fulfil its own obligation of supporting the development and validation of alternatives that it put into the White Paper. The Commission should take the Guideline 86/609 at least as serious as in the past when it created ECVAM. He, therefore, proposed that the Commission should earmark at least 20 million Euros in the 6th Framework Programme for the development and validation of alternatives. The outcome of the seven ongoing working groups was to be fed into a yet to be defined process within the DGs identifying chances and funding schemes for alternative methods development. In that regard, ecopa would offer its assistance for the identification of the process, of the respective experts and for the organisation of an appropriate workshop.
Dr. Sauer mentioned that ECVAM had already produced a document addressing the different endpoints that would be discussed at a stakeholders’ conference and asked what the difference was between an ecopa organised stakeholders’ conference from that of the ECVAM organised one. He replied that if ECVAM were to present a number of validated methods and to show again that there are validated methods already available in certain areas, then that is laudable. But ECVAM is part of the Commission and therefore it cannot deal with political issues. This was where ecopa came in since it could make provocative political statements that ECVAM could never make.
Dr. Vogelgesang added that ECVAM was currently preparing a collection of alternative methods that will be ready early next spring. According to his information, a draft was already available and would be provided to the testing working group that had been installed earlier. Regarding the issue of the estimated 10 to 12 million animals that would be used, Dr. Vogelgesang argued that such a figure would only be imaginable in the case of box-ticking testing but that was not intended. The gathering of existing information and data was essential and the White Book foresaw already conditions for waiving tests. Therefore no realistic estimate regarding the animals to be used can be given but it should surely be much lower than the estimated 10 to 12 million mentioned.
Concerning the costs they would have to be seen in regard to the total yearly turnover of the European chemicals industry to be running at 400 billion Euros. If industry did all the tests as outlined in the White Book and would want to get reimbursed for the costs within one year, estimates were that it would have to raise prices by a mere 0.04 per cent for that one year.
Dr. R. Taalman: View of the (European) Chemical Industry and CEFIC
Dr. Taalman was to focus not only on the view of the chemical industry but would also provide information on what the industry was doing to bridge the gap between science and decision-making with respect to alternative methods.
In the first part he provided background information regarding the history and objectives of the White Paper. Current chemicals policy was based on the Treaty of Rome with two main aspects of chemical control, that is chemical specific control and chemical exposure control. While the first was practiced at the European level the latter was usually done through emission limits and best available practice at the national level.
Also industry felt that the old system was not fit to meet either the expectations or the new challenges. The Commission therefore proposed the White Paper as a step by step approach to phase out and substitute the most dangerous substances, that is those causing cancer, accumulate in the body and in the environment and effect the ability to reproduce. Though industry agrees in principle, it stressed that the focus should be on pre-market rather than on pre-manufacturing in order to save time, money and animals. With respect to the timeframe given in the White Paper, it was too optimistic; it would take much longer to gather all the information and run all the necessary tests. It was thus that industry would have serious doubts concerning the feasibility.
He re-numerated the key points such as the reversal of the burden of proof, the precautionary and the substitution principles, sustainability, a stricter registration system, a tightening of testing deadlines for marketing substances and the stimulation of innovation and competitiveness. Non-animal testing was only one of the White Paper’s subsidiary objectives.
The industry on its part has responded with a global initiative to address emerging and existing health and environmental issues through independent research. This so-called Long Range Research Initiative (LRI) shall provide for information that decision-makers need in this field and help to create a broad consensus for scientific research needs and directions. Its focus is on bridging the gap between research and policy that is to create a research programme that responds and adds to scientific knowledge in the light of regulatory and societal developments.
CEFIC (European Chemical Industry Council) strongly supports all efforts aiming at limiting animal testing to the utmost possible without compromising human health and/or the environment. Industry was working on the development of alternative methods and CEFIC-LRI was funding projects in this area and collaborating closely with academics and regulatory authorities. Industry was committed to testing through consortia to avoid unnecessary duplication. But also harmonisation of regulatory schemes would help to reduce animal testing.
A future chemicals legislation will be based on exposure based, hazard based and risk based decisions. Research in the chemicals sector should thus provide results, which can improve efficiencies and the scientific base within each of the 3 decision mechanisms. It should also inform policy judgements regarding the balance between the 3 decision mechanisms to meet the current and future economic, environmental and societal needs.
CEFIC therefore recommends that with respect to exposure based decisions there was a need for the development of cleaner production methods while for effective exposure control there should be a monitoring of chemical substances in the environment. Besides, early warning systems for subtle eco-system changes should be developed, for example through biomarkers. Concerning hazard and risk based decisions; there should be an improvement and rationalisation of RA procedures as well as an estimation of long-term effects and risks from exposure to chemicals. Dr. This would entail various detailed research needs such as the development of alternative tests or the evaluation of the sensitivities of specific populations.
Research should improve the basis for a balanced risk management. This would entail a study on the total impact of risk management decisions (triple bottom line), the development of methods for decision makers to compare potential health and environment risk reduction measures with economic and societal costs benefits.
In addition to the White Paper, the future would bring an increasing demand for testing due to such issues as HPV, endocrine disrupters and so on. Thus, there was an increasing need for tests that would be resource efficient, globally accepted, and scientifically valid and use fewer animals. Methods for developmental effects in humans and wildlife would have to be improved and additional alternative methods were evaluated, e.g. transgenic animals and QSAR approaches.
With respect to QSAR approaches, the Danish authorities had developed QSAR based advisory classification system for environmental and human health endpoints. LRI had set up a working dialogue with DEPA to foster use of QSARs for C&L and RA. The Netherlands and Canada were now going to initially screen all chemicals in use by QSARs. Future LRI activities would include a workshop on the use of QSARs in hazard and risk assessment and proposals to develop a global system for data depository & hazard assessment prediction would be solicited.
U. Sauer: View of the Animal Welfare Associations
One key element of the White Paper with prime relevance for animal welfare is the promotion of non-animal testing. According to the White Paper, the use of non-animal test methods should be maximised and test programmes minimised while the development of new non-animal test methods would be encouraged. There were a couple of statements on the implementation of these elements with respect to animal welfare. Data of chemicals with production volumes from 1-10 t/yr should basically be derived from non-animal tests. Flexibility was to be applied in the testing strategy and tests omitted when the data obtained was unnecessary.
However, Dr. Sauer questioned whether the White Paper did enough to ensure safety for humans and the environment and to avoid the use of animal tests. Actually, the White Paper contained no specifications on how to maximise the use of alternatives and to minimise the use of animal tests or to achieve flexibility in the testing strategy. In particular, the non-animal testing strategy for low production volume chemicals was not specified and it was not even clear, if that strategy would only apply to those chemicals or others, too. Risk management, safety testing and waiving strategies as well as funding for the development and validation of alternative test methods were to be included.
Risk management strategies would be the appropriate starting point for developing a new chemicals policy. One should decide on actions to be taken when a chemical is found to have certain hazardous properties. Then it was necessary to identify and prioritise the need for particular types of information before the decision is taken on the most appropriate method to obtain this information. Once a risk management strategy was defined it would help to avoid animal tests since it would enable to stop testing at very early stages when specific unwanted effects have been detected.
For safety testing an integrated tiered testing strategy was needed. First of all, the existing information on a substance should be collected and a hazard prediction be made based on its structure (i.e. QSAR). Then physic-chemical properties, persistency and bioaccumulation tests should be made, to be followed by batteries of basic in vitro tests (cytotoxicity, mutagenocity etc.) as well as batteries of specific in vitro tests (cell transformation, specific cell types such as embryonic stem cells, hepatocytes or neurons). Only when all these steps had failed to produce the necessary information, one should consider the option of animal tests. The key element of this tiered approach, however, would be to evaluate the information after each step in order to decide whether a classification was already possible which would render any additional testing obsolete.
She made the case for a waiving mechanism that would serve as a clear strategy with guidelines on when to omit which tests. Official guidelines (decision trees) for the testing strategy were to be developed and the testing tailored to the results of the available information, physico-chemical properties, the use and the exposure to the substance. These guidelines would have to allow for every possible opportunity to avoid animal testing and to classify a given chemical making use of the minimum information necessary for that purpose.
Finally, with respect to the funding of alternative test development and validation immediate action was imperative if significant progress was to be made in time to have an impact. This, however, required a substantial amount of funding. The funding of alternative test development and validation should therefore be prioritised in the 6th Framework Programme. The focus should be on tests with the greatest potential to save animals in regard to registration of existing chemicals. Safety for humans and the environment could be achieved through concrete risk management and new safety testing strategies without animal tests.
Asked by Prof. Maier if she made a distinction between the support of pre-validation/validation studies and the support of so-called 3-R-research she replied that one follows from the other. If there was a method ready for validation then one should start with the validation. If there were a scientific idea then first of all one would need a method that was ready for validation. She felt that this was a stepwise process.
Dr. Kayser asked about the problem of timing for developing and using new alternative methods, Dr. Sauer appreciated the tight timeframe laid out in the White Paper since it would force people to start doing things. On the other hand, however, she felt that time should not be wasted but that one should get started now. One should get started to get things done.
With respect to the timing Dr. Garthoff added that one problem with the given timeframe was that it would raise expectations with the general public that could not be met. It would thus be better to use a more realistic timeframe and inform people of the actual situation in order to avoid disappointment. Needless to say that there was no reason not to get started right away to get things done.
Dr. Bansil expressed his favour for waiving mechanisms as one of the most suitable tools to get rid of redundant animal testing. However, in the past there had been great trouble to get guidelines from the authorities, which he felt was primarily due to reviewers feeling very uncomfortable of putting such guidelines down on paper. He asked Dr. Sauer whether she saw any concrete steps that scientists could take to change attitudes. She was wondering whether the reversal of the burden of proof was a first step into this direction. This would lead scientists in industry to waive tests and to explain the reasons that let to this decision. The reviewers would thus be confronted with issues more often and eventually be forced to provide guidelines for all levels.
Dr. Ph. Botham: View of a Toxicologist
Dr. Botham posed the question whether a new strategy was actually needed, and explained indeed why. A new chemicals policy was needed in order to achieve a better balance between hazard data and knowledge of exposure, to achieve greater transparency and also to ensure that existing data was more widely available and its quality would be reviewed, particularly the pre-GLP studies.
But the White Paper gave not the appropriate strategy to achieve these objectives. There were a number of reasons supporting this view. The White Paper for example would retain tonnage rather than usage as a main trigger for determining testing requirements, set unrealistic timelines and might include endocrine disrupters and possibly also sensitisers in the authorisation process. It would further threaten the competitiveness of the European chemical industry, increase administration costs for the EU and finally increase the number of animals being used as high as 12.8 million.
Dr. Botham illustrated that the base set would have to comprise tests for acute toxicity, skin and eye irritation, skin sensitation, mutagenicity and sub-acute toxicity. Further, level 1 would have to include tests for fertility and teratology studies, sub-chronic and/or chronic toxicity, additional mutagenecity as well as basic toxicokinetics information. Finally, Level 2 would have to comprise tests for chronic toxicity, carcinogenicity, fertility, developmental toxicity and additional toxicokinetics studies as well as additional tests to investigate organ or system toxicity.
Since it was naive to believe that all those tests could be replaced by alternative methods it was sound to believe that the number of animals used in addition would be high. However, there were already a number of possibilities to reduce that figure of 12.8 million animals, even without in vitro alternatives. Quoting from the White Paper, he referred to such provisions as no animal testing for chemicals of 10kg to 1 ton production volume per year or the limitation to in-vitro tests for chemicals of 1 tonne to 10 tonnes production volume per year.
With reference to the USA High Production Volume Chemical Challenge, the US had created a precedent for lower actual animal usage by introducing a so-called “Test Smart” scheme. Based on a voluntarily commitment by the producers to fill the data gap on 2800 chemicals as well as a response by the in vitro community, led by. Johns Hopkins CAAT, Test Smart came into being. Today is was being lauded as an “humane and efficient” approach to collecting data based on OECD-SIDS tests covering the whole range from acute and genetic over developmental to reproductive toxicity. The steps involved in developing Test Smart included an evaluation of existing OECD protocols and what scientifically validated alternatives were not yet approved or adopted by the OECD or needed validation and further research.
The conclusion of Test Smart was that on an individual basis the animal use could be reduced from an average of 440 down to 88 per chemical. This conclusion had been accepted by the Environmental Protection Agency in the USA in 1999 and as matters stood, producers would now be encouraged to use Test Smart in their daily work.
Dr. Botham furthermore explained why and when a toxicologist in industry would feel encouraged to use alternatives. Any alternative method to be accepted by toxicologists would have to provide the same level or even better quality information on hazard or risk to man than animal tests. There was no point in putting forward an alternative method if it did not meet this main requirement. They would be favoured in case they were cheaper and quicker to use and if the regulatory authorities (preferably worldwide) accepted them.
In order to comply with the EU Chemicals Policy and to minimise animal use he suggested identifying the most toxic chemicals to allow prioritisation of risk management and to identify the most important hazard endpoints associated with these chemicals. It should furthermore be evaluated what was in place that could be used right away as well as what could be ready for use in time for the White Paper timetable.
Preliminary conclusions of the ECVAM Chemicals Working Group in this regard were that chemicals should be prioritised in terms of potential bioavailability as well as potential exposure. In vitro based cytotoxicity tests and in vitro metabolism screens should be used as medium throughout screens to predict the most toxic chemicals. Since in vitro tests for skin corrosion and photo toxicity had been validated, they could be used alongside other validated in vivo tests, which would give improvements in the 3R’s, that is for acute oral toxicity and skin sensitisation (local lymph node assay).
Validation and acceptance of in vitro tests for skin irritation (e.g. reconstituted human skin models such as Epiderm and Episkin) and developmental tox and the in vitro micronucleus test should be accelerated and completed within the next three years to allow their use as replacement tests. Development of in vitro test batteries for predicting acute, chronic and reproductive toxicity as well as toxic kinetics and in vitro approaches for predicting skin sensitisation and carcinogen city required significant investment in research that should be funded partly though the 6th EU Framework Programme. Yet, validated tests in these research areas were unlikely for at least another 10 to 20 years.
He concluded that due to exceptions, prioritisation and data sharing; the EU Chemicals Policy would in effect require far fewer than 12.8 million animals to be used. Alternatives would be used, but not always in-vitro alternatives. He also highlighted the need for investment in research, development and validation of alternatives but stressed that it should be based on high quality scientific proposals. As a closing remark, he insisted that the protection of human health was paramount and that the development of alternatives could not be justified on ethical grounds alone.
Dr. Vogelgesang disagreed with Dr. Botham on his conclusion that the White Paper was not the right answer to the chemicals issue. He also stressed that the White Paper did not state anything about including endocrine disrupters in the authorisation process. Dr. Botham clarified that the inclusion of endocrine disrupters was actually not stated in the White Paper but that various people had suggested such a move.
Prof. Rogiers referred to the estimate that for long term testing it would take another 10 to 20 years. She wondered how that would be reflected in the ECVAM scheme since there were statements that problems could actually be solved in 5 years. Dr. Botham, himself serving on the ECVAM chemicals working group, replied that the figure of 10 to 20 years was his personal view which he felt was even an optimistic one.
Dr. Bansil expressed his view that money was not the only issue but that it took basic fundamental research and thus time to come up with new alternative methods. He also pointed out that developing and validating was one side but that acceptance of alternative methods was an equally challenging and time consuming task that required more attention.
Prof. H. Spielmann: View of an Institution for Implementation of Alternatives
Prof. Spielmann illustrated that article 7.2 and 23 of the EU Directive 86/609/EEC formed the basis for developing alternative methods. Meanwhile a number of centres for alternatives to animal testing had been founded in various European countries such as the NCA in the Netherlands, BGVV/Zebet in Germany or the European Centre for the Validation of Alternative Methods (ECVAM) at the IHPC JRC (Joint Research Centre) in Ispra, Italy.
He further explained that ECVAM’s mission according to ESAC (European Science Advisory Council) was 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. As a Commission communication of 1991 outlined the duties of ECVAM were to co-ordinate validation of alternative test methods at the EU level and to act as a focal point for the exchange of information on the development of such methods.
The ECVAM Working Group on the Integrated Use of Alternative Test Methods and Strategies, had proposed immediate action in March 2001 and would be reconvened to consider the implications of the White Paper on A Strategy for a Future Chemicals Policy. A conference involving invited experts and stakeholders would be held before the end of 2001 to consider the proposals made by the ECVAM working group.
Arguing that though there was a number of reasons – scientific, economic, logistical, ethical, legal and political – to further the development and implementation of alternative methods, he stressed that there were various factors affecting progress in this regard. Progress would be affected for instance by the development of candidate new test methods for pre/validation, the provision of adequate funding, and the availability of experienced laboratories as well as trained personnel to design and manage the studies properly. The willingness of industries and regulatory authorities to accept scientifically valid alternative test procedures and testing strategies was another factor to be kept in mind.
Nevertheless there was a list of 10 alternative methods which would be considered to be scientifically valid by ECVAM, for example the EPISKIN and EpiDerm tests for skin corrosivity, the micro mass embryo toxicity test and the 3t3 NRU photo toxicity test for photo toxic potential. Other areas could have validated replacement alternative methods within five years. These included eye and skin irritation, skin sensitisation and penetration, nephro toxicity, hepato toxicity, neuro toxicity, the blood-brain barrier, acute systemic toxicity and chemical carcinogen sis.
He gave detailed examples made by the ECVAM Working Group on the Integrated Use of Alternative Test Methods and Strategies. Regarding eye irritation, a number of tests for the identification of severe irritants were accepted by regulatory authorities in several EU member states: The Bovine Corneal Opacity & Permeability (BCOP) test or the Hen’s Egg Test – Choric-Allantoic Membrane (HET-CAM) test to give a few examples. Yet, the irritation system (formerly Eytex) was not recommended due to the lack of a standardised protocol and poor in vitro-in vivo comparisons. ECVAM would therefore conduct a survey to find out how these methods were used by industry. The survey should specifically request details of any prediction models used.
Concerning skin irritation, two organotopic human skin models were considered to be promising alternatives, namely EPISKIN and the EpiDerm; in addition, an ex vivo method, the Skin Integrity Function Test (SIFT). Prof. Spielmann added that an ECVAM pre-validation study had assessed the relevance and reliability of these tests. The ECVAM Skin Irritation Task Force would currently be re-analysing the data obtained to determine whether minor changes in the protocols and/or prediction models could improve the relevance and/or reliability of these tests. A report was currently being prepared.
With respect to skin corrosion, two kinds of tests had been validated, that is an ex vivo method called the transcutaneous electrical resistance (TER) test and secondly human skin equivalents that meet certain criteria (EPISKIN, EpiDerm). The working group concluded that action in this area was not required urgently, since alternative methods had been validated and accepted by the EU regulatory authorities. However, the development and validation of new humane skin models would increase the range of available alternative tests for skin corrosion.
Regarding skin sensitisation, a refinement animal method – the local lymph node assay (LLNA) – had been endorsed by ESAC and various others were thought to be useful, e.g. the computer based expert system, Deductive Estimation of Risk from Existing Knowledge (DEREK), protein-binding assays and dentritic cells that synthesise and release 1L-1b. The working group acknowledged that a retrospective review of the sensitisation potential of existing chemicals was required and that a common protocol for protein-binding assays was needed.
ICCVAM had held a workshop on alternative methods in 2000 to address the topic of acute systemic toxicity. A number of cytotoxicity assays were available and considered to be sufficient for hazard classification based on rough estimates of LD50 and a pre-validation study was run on the use of 373 cells and human keratinocytes or predicting acute toxicity. ECVAM would participate in a feasibility study on the prediction of human MTD values from in vitro cytotoxicity data.
As far as the repeated dose (28-day) toxicity was concerned, the contribution of the 28-day study to the overall information was currently being evaluated, since this test would not be part of the proposed new base set of testing. There were no widely accepted in vitro systems for repeat dose toxicity testing available. ECVAM was currently involved in the development of in vitro methods for chronic toxicity testing, which may be suitable for pre-validation in the near future.
Regarding mutagenicity, three in vitro tests was recommended, e.g. micronucleus assay, a bacterial mutation assay and mammalian in vitro cytogenetics assay. With respect to carcinogenicity, cell transformation assays were considered to be the most promising alternative, for example the Syrian hamster embryo (SHE) assay or the MSU-1 (human) cell line. Yet, the development of a reliable and relevant cell transformation assay was required. This test should preferably be derived from human cells and should be capable of detecting genotoxic and non-genotoxic carcinogens.
In reproductive toxicity, the animal test covered a wide range of effects, so that a number of alternative tests would be required to replace or significantly reduce the use of the animal test. No methods had been identified that would be suitable for pre-validation in the near future. So far, developing in vitro tests for assessing effects on tissues of the female and male reproductive organs seemed promising (Leydig or ovarian follicle cells).
The White Paper signified a general improvement since data on hazardous chemicals would be obtained earlier than previously. Calling the new concept a realistic one, in vitro tests would be cheaper to conduct and would provide data faster and that costs for industry would be moderate. Within an acceptable time frame the new data would allow both hazard assessment and risk management for existing chemicals. The working group had elaborated and proposed an integrated testing scheme for existing and new chemicals that would indeed emphasise the use of in vitro methods to reduce the number of animals needed.
The White Paper furthermore signified an improvement of ethics and science there would be a higher quality of research to replace testing in animals according to the 3Rs concept of Russell & Burch. The use of human tissue from surgery and genetically manipulated human cells and tissues may raise ethical concern. It would thus be essential to amend the legal framework in Europe to progress in the biological sciences.
Dr. J. Huggard: Policy on Chemicals: Is there a right or wrong?
Over the past decades the notion of risk, though difficult to quantify and to pin down, had become one of the dominant themes in politics as well as public opinion. There was a general public desire to be protected from any kind of visible or potential risk whatsoever. The growing number of pressure groups was evidence to this claim and yet at the same time a sign that people did not want to worry about everything himself or herself but preferred to allocate trust to such interest groups.
This was also true in the case of the EU chemicals policy, which eventually lead to the White Paper. The current EU chemical control laws had grown from a single directive in 1967 into a complex and often confusing network of rules, e.g. the existing Substances Directive, No. 793/93 (ESR) was the target of most of the criticism and indeed it was widely acknowledged that the current system did not work. There was a slow rate of progress regarding risk assessment. By July 2001 the risk assessment had been completed for a mere 47 substances and full results had only been published for 6 substances.
In 1998, the Commission had therefore been asked by the member states to review the EU chemical policy, which then called for an overhaul of this policy. This lead to the current EU White Paper which was adopted by the Commission in February 2001 and presented to a number of councils afterwards, e.g. the environment council, the internal market/consumer affairs/ tourism council and the energy/industry council.
After reviewing the White Paper the energy/industry council had concluded that it was important to ensure European industry’s competitiveness with industries outside the EU. It was thus deemed essential to consider the cost-effectiveness of the new system as well as incentives for innovation. The need was also seen to ensure a balanced burden sharing between upstream and downstream chemical industry and to take into account the interests of small and medium-sized enterprises.
The environment council on its part had concluded that there was a need for a “duty of care” obligation for manufacturers and that the Commission should propose how to deal with substances in finished products manufactured or imported. The council generally supported the registration schedule but wanted the Commission to develop a flexible system allowing for prioritisation for assessment. It furthermore endorsed the principle of authorisation for substances such as PBTs, VPVBs, and known endocrine disrupters with use being permitted only in justified cases.
The Environment Committee of the European Parliament had recently voted and adopted the report by 31 to 21 votes that would seek to strengthen many aspects of the White Paper such as including endocrine disrupters, sensitisers and CMR categories 1,2 and 3 or registering all chemicals with production volumes under 1 tonne as well as those over 1 tonne. It had also been stated that the EU should move towards a qualitative risk assessment.
“A non-toxic Europe”, enhancing innovation and the competitiveness of the industry as well as creating a clear framework for industry were the key promises of the White Paper, though nobody really knew what “a non-toxic Europe” would actually mean. As an impact of the White Paper, the estimated testing costs of Euro 2.1 billion were only the tip of the iceberg and would thus in practice be detrimental to the promise of enhancing competitiveness. Giving the example of testing in the animal health industry he illustrated how the European Regulatory Framework had negatively influenced innovation over the past 10 years leading to business closures, fewer products and the relocation of R&D resources. Therefore, the Commission’s hope that the new chemicals policy would promote innovation was a pious hope based on false assumptions, such as that industry would need this spur to develop more profitable products and that it would be cheaper to innovate than to defend. He thus predicted a loss of marginal chemicals and a more defensive R&D strategy.
Standard sets of data sets, unified testing programmes based on validated protocols and cross jurisdictional acceptance of testing methods are wanted by industry. In addition, an authorisation process that only applied to chemicals classified as hazardous under internationally agreed protocols, as well as a consideration for socio-economic factors. Dr. Huggard asked whether one believed that the new chemicals policy would deliver a “non-toxic Europe” or that there would be a net benefit to European citizens being worth the effort?
Asked by Dr. Garthoff what he would consider a net benefit to the European citizen, Dr. Huggard replied that it was a matter of degree. Looking at the current level of protection, he argued that the present mood was to improve it whilst he wondered if that was really worth the price. He felt that this whole issue had not been well thought through at first and that some points needed to be reconsidered.
Dr. E. Sandberg: A governmental View: Torn between Health and Environmental Concern and Lab Animal Death
Dr. Sandberg provided background information regarding the Swedish policy on chemicals. Faced with such issues as PCB, DDT or mercury – just to give a few examples – and the subsequent negative environmental consequences, the Swedish government and parliament decided that action needed to be taken. Yet, the objective was not only to solve existing problems but also to find a way of dealing with chemicals in a way that neither old nor new chemicals would cause new risks in the future. In 1998, the Swedish government thus presented to the parliament an environmental bill comprising 15 different environmental quality objectives. This bill called “Environmental Policy for a sustainable Sweden” included the creation of “a non-toxic environment” as one of its key objectives.
The Swedish parliament had also tried to define an overall objective that was called the “generation” objective, meaning that the next generation should live in a society in which the main environmental issues were solved. To achieve this objective, however, meant that the environmental problems would have to be solved within the next 10 to 15 years.
The different environmental quality objectives required further definition and clarification. This was the point where the notion of a non-toxic environment came in, meaning that the environment should be free from man made substances and metals that represent a threat to the health and biological diversity. It also meant that the levels of substances that were in the environment should be close to background levels and the levels of man made substances should be close to zero. These and additional clarifications were then included in a follow-up bill that was submitted and passed in 2001.
Due to the given timetable there was a clear need for a speedy evaluation of substances which the existing framework could not provide. The Swedish government acknowledged that data would be required for all HPV and other chemicals. Yet, in order to avoid unnecessary animal testing a tiered approach for risk assessment was chosen.
In Sweden certain substances with certain inherent properties should not be used at all in order to avoid the negative experiences made in the past for example with PVB or DDT. Also substances that are persistent and liable to bio accumulate should not be used at all since they would always pose a risk due to accumulation in the environment. Once a problem arose it would almost be impossible to clean it up again. One should therefore take preventive action. There was also agreement in Sweden that a chemical with a half-life longer than 26 weeks and a bio concentration higher than 5000 should not be on the market at all.
The parliament also suggested that endocrine disrupters and sensitisers should be included in the authorisation process later on. Taking these aspects as a starting point, it would be possible to reduce the number of animal tests right form the beginning. Indeed, it was included in the bill that testing should be done in the best way possible, e.g. with as little animal testing as possible.
Yet, there was a need of data for chemicals that were not known to be persistent and bio accumulative. This tiered approach, however, gave the opportunity for a smart way of testing providing for evaluations after each step and the option to waive further testing once the data obtained was deemed to be sufficient. This stepwise approach should also be part of the Community legislation.
There was a need for improved testing methods as well as additional methods for other endpoints that would not be available today on an agreed basis. In addition, there was a need for improved methods with respect to bioaccumulation and degradability.
The bill also contained a direct reference to the issue of animal testing by stipulating that animal testing should be reduced be means of developing more alternative methods and more accurate models for accumulative properties as well as promoting the validation of such methods.
Since the bill got presented and passed, there had been additional preparatory work resulting in different action programmes and related timeframes. Regarding short-term initiatives, it was decided that the OECD work in the field of alternative methods should be supported strongly. At the request of the OECD, Sweden would organise a conference on alternative methods in 2002 and perhaps second an expert to the OECD. In the medium term, the emphasis would be on developing and validating alternative methods as well as supporting organisations to do such work. The long-term activities would then focus on supporting research at the national and European level as well as providing the respective funding.
The Swedish government would increase spending allocated to the Central Board for Laboratory Animals for animal welfare and alternative methods purposes over the next three years from 5 to 10 and eventually to 15 million SEK.
There was a clear need to know more about the chemicals that are being used today, yet, necessary information should be obtained in a smart way, using information sharing, alternative methods and other means to avoid animal testing as much as possible, ensuring that all the required information was available to take the best decisions to protect the human health and the environment.
Asked by Dr. Garthoff about the timeframe of the Swedish government, Dr. Sandberg replied that it was based on the next generation goal, which actually meant the year 2020. The Swedish timeframe was even stricter than the one proposed in the White Paper due to the fact that the Commission’s proposal was not known yet when the Swedish government submitted its bill to the parliament.
Prof. Thorn asked about the rational of supporting research at the national level in comparison to ECVAM at the European level. Dr. Sandberg replied that the work of ECVAM was highly appreciated by the Swedish government but that there was also a long history of supporting research on alternative methods. Thus, the prevalent view in Sweden was that funding at the national level was still very important and should continue. Indeed, research at the European level should not prevent countries from having their own initiatives. In this regard ecopa could play a constructive role in collecting and disseminating information on such projects in the different countries.
Dr. E. Walum: Possibilities for Pre-screening Alternatives
Dr. Walum focused on presenting MEIC and ECITTS study results that may guide to future developments of in vitro methods for the assessment of acute systemic toxicity.
The MEIC-program, conducted under the auspices of the Scandinavian Society for Cell Toxicology, was a multicenter program to evaluate the relevance for acute human systemic toxicity of in vitro cytotoxicity tests. At the closure of the experimental part of the program in the summer of 1996, 29 laboratories had tested 50 reference chemicals in 61 cytotoxicity assays.
To provide a background to the in vitro/in vivo evaluation, mouse LD50-values were compared with human lethal doses, resulting in a good correlation (R2 0.65). To study the relevance on in vitro results, IC50-values were compared with human lethal blood concentrations (LCs) by linear regression. An average IC50 for the ten 24h human cell line tests predicted peak LCs better (R2 0.74) than other groups of tests. When IC50-values for 32 chemicals, which rapidly enter brain were divided by a factor of 3.2 and 48h IC50-values were compared to 48h human LCs for ten slow-acting chemicals the prediction improved considerably.
Human toxicity was clearly under predicted for only four chemicals, e.g. dioxin, malathion, nicotine and atropine, indicating a high relevance of the human cell line toxicity. All chemicals entering brain induce a CNS-depression, explaining this syndrome as a cytotoxic effect. Multivariate analysis was used to select an optimal combination of assays, resulting in a battery of three 24h human cell line tests (endpoints: protein, ATP and morphology/pH) with good direct prediction of human peak LCs (R2 0.77) The results of the study have been published in ATLA.
Fundamental to the MEIC-program was the idea that the prediction of systemic toxicity from cytotoxicity data may be improved by adding information on bio kinetics. The ECITTS-project would aim at defining the criteria for an integrated approach to the prediction of systemic toxicity using computer-based bio kinetic models and biological in vitro test methods. A first study, aiming at predicting LOELs for selected neurotoxic chemicals had been completed and generated encouraging results on the possible methodologies of risk assessment. A test scheme, using highly differentiated human neuroblastoma cells (SH-SY5Y) was applied (endpoints: protein, morphology, rate of protein synthesis, calcium homeostasis, activity of voltage-operated calcium channels and activity of muscarinic acetyl choline receptors) and combined with kinetic simulations and QSAR analysis.
The discrepancy between estimated and experimental LOELs ranged from a factor of two, for compounds with a low toxicity, to a factor of 10, for compounds with a high toxicity. It should be noted that LOELs of the most toxic compounds (diazepam, parathion and paraoxon) could only be established after consideration of in vitro test results that were derived from the literature.
The results show that the LOEL estimation for acryl amide benefited from an extended testing protocol for this compound. This extra information would allow for an estimation of acute, sub acute and sub chronic toxicity of acryl amide with a high degree of accuracy. Though, for caffeine, phenytoin and lindane LOEL predictions were less accurate, they were still acceptable.
Prof. A. Vedani: In Silico Prediction of Harmful Effects triggered by Chemicals
Prof. Vedani explained that the objective is to establish a virtual laboratory on the Internet to allow for an in silico estimation of harmful effects triggered by drugs, chemicals and their metabolites.
The current database included validated models for five biological targets – the Aryl hydrocarbon, 5HT-2A, cannabinoid, GABA-A, and steroid receptor, respectively. It will be continuously extended to include surrogates for any bioregulator known or presumed to mediate harmful effects.
Free access to this virtual laboratory will allow any interested party to estimate the harmful potential of a given substance prior to its synthesis. This is achieved by generating the three-dimensional structure of the compound and its possible metabolites in the computer, followed by calculating their binding affinity towards each receptor surrogate in the database.
Only compounds/metabolites passing through this surrogate battery without displaying a significant affinity towards any member should be cleared for synthesis and pre-clinical studies.
Prof. Vedani concluded that this way potentially harmful compounds could be withdrawn from the evaluation pipeline before in vivo test were conducted, hence contributing to the reduction of animal testing in chemical and pharmaceutical research and development. Additional information is available on the Internet at www.biograf.ch/ecopa.
Asked by Dr. Garthoff about the structurally more simple compounds, Prof. Vedani replied that any compound could be handled using this model. With the computers currently available it would take about twenty minutes to shuttle a compound through 50 surrogates. It was even possible to download this database from the website and run this simulation on the own computer. The goal was to frequently update this database with receptors for which the immediate toxicity would be known or anticipated.
Prof. Castell asked whether this model would also apply with respect to peptides. Prof. Vedani explained that there were problems with peptides, especially if they were not ring structures since they would come in different shapes. This would in turn cause problems with the five dimensional QSAR that were being used.
Podium Discussion: The Way Forward?
Dr. Bansil moderating this session introduced the speakers, e.g. Dr. Walum, Mrs. Gabrielson, Dr. Vollmer and Prof. Bolt, and opened the discussion by asking whether they believed that the 3Rs had been considered to the fullest extent in the White Paper.
Dr. Vollmer replied that this was a difficult question to answer since he hoped that by the time the White Paper came into effect there would be many more alternative methods available than today. In addition, he thought that reduction did not just mean to use another method but it would also include deciding beforehand if a method was needed at all whether it was an alternative one or based on animal testing. Comparing the current risk assessment that was first introduced in 1993 with the new policy foreseen in the White Paper, he pointed out that a major advantage in the future would be to have data on the use and exposure of all chemicals. Any kind of decision for further testing for instance would thus be based on both the information available right from the beginning but also on use and exposure. A central database would be installed for this purpose. He also complained that usually all assessments were based on animal testing but hardly ever on data derived from accidents with humans though such results could be used and provide valuable information.
Mrs. Gabrielson disagreed and expressed her view that the 3Rs had not been considered well enough in the White Paper. She stressed that the 3Rs had only been included in the White Paper after criticism from different groups and organisations such as ecopa or Eurogroup. And yet there were only words in the White Paper but no hard facts regarding funding and the allocation of resources but that was what was really needed.
Prof. Bolt basically agreed since he felt that the issue itself had been sufficiently addressed in the White Book but he missed an in-depth analysis of the problem. The White Book lacked a very basic thing, e.g. the kind of testing strategy to be applied. He pointed out that there seemed to be a general consensus at this workshop that a series of tiered approach was necessary combining different methods and models to reduce the number of animal testing. From a scientific viewpoint, he added, that there was considerable progress made but that validation and especially the transformation into legislation at the EU and OECD level would still be a major problem to be dealt with.
Dr. Walum said that as long as there was no actual funding provided, one could not say that the 3Rs were taken fully into account. He furthermore believed that for the future the 3Rs would not be a good starting point for the decision. He said that one could not just talk about replacing animal testing and think that replacing in vivo methods would lead forward. Instead, it was necessary at the time to develop methods that provide the basis for decisions on the toxicity for which there were not any animal counterparts available.
Referring to Dr. Walum’s view, Dr. Bansil stressed that the 3Rs did not focus exclusively on replacement but that it also included refinement and reduction. Picking up Dr. Vollmer’s remark about using data derived from accidents, he then asked the speakers whether they considered human experience data a valid alternative for risk assessment.
Dr. Vollmer stressed that there was a need to establish more links to be able to use this information. But in terms of safety data it would not be used as an alternative testing since legislation worked the other way around, e.g. first to use data from animal testing before considering additional data.
Prof. Bolt hinted that there were two major sources, e.g. the material on acute poisonings on the one hand and the occupational toxicology field on the hand. He thought that both for daily practice and research purposes, it was very important to pinpoint the relationship between the animal toxicity data and the human toxicity data whenever possible. Though, one should keep in mind that there was always a chance of unexpected differences as cases in the past had shown, it would be very important to use the data where it was available.
Dr. Botham stressed that there were some basic philosophical differences about the use of human data in the various EU member states. While some countries condoned the use of such data, others outright condemned it. In this regard Dr. Vollmer clarified that he did not imply to run studies with humans but only wanted the already existing and available data to be used more.
Dr. Bansil then asked about the concrete steps that should be taken with respect to a better inclusion of the 3Rs.
Dr. Walum saw a need to emphasise the possibilities for alternative methods and to address the question of the right limiting step in developing and implementing alternatives. He said that there were different views. While some felt that validation was too slow, others regarded the process of acceptance as a major limiting factor. His personal view was that there were tests and that validation worked so that for him acceptance was the key issue.
Prof. Bolt stated that taking the entire menu of toxicological school book testing then with respect to acute toxicity there had already been some development for example in the field of toxic class methods as related to the classical LD50. He also said that such fields as irritation, corrosion, sensitisation and skin absorption tests were important areas that should see practical results with respect to the legal realisation in the relatively near future.
Dr. Vollmer replied that they (the ECB) were waiting for more alternative methods to be brought forward by the member states to get them validated and implemented.
Mrs. Gabrielson stressed there was a need to look at the strategies again in order to reassess how the use of animals could be minimised by such measures as exceptions, waiving and testing requirements and so on. Another step would be to validate existing alternative methods that had not been validated yet. She also saw a need for working groups such as the ecopa and ECVAM ones to identify which methods were ready for pre-validation or validation, needed to be improved or missing and would thus require further research. In addition, she highlighted the necessity of more resources including funding for research, which should become a priority in the 6th Framework Programme allocating 20 million EURO to this purpose. Furthermore, the validation procedures for alternatives should be speeded. Finally, education on alternative methods and their availability should be stepped up with particular emphasis on informing small and medium sized companies since they would often lack the appropriate information to use alternative methods in their daily work.
Asked by Dr. Bansil whether any of the speakers thought that methods, which had just finished its validation, should be used even if they were not legally installed yet, none of the speakers considered this as a viable option.
Dr. Bansil then asked whether the additional funding for research on alternative methods should only come from the Commission or also from other stakeholders such as industry and animal welfare.
Dr. Sauer speaking on behalf of the animal welfare movement replied that animal welfare organisations were non-profit organisations depending on membership fees. She stated that the money available was thus barely enough to finance the organisation’s basic work, e.g. animal shelters and so on. It would thus not be possible for them to contribute financially to such research projects. In contrast, she felt that industry which actually profited from animal experiments should provide funding in addition to government resources if that was desired. The animal welfare movement on its part would be happy to contribute its expertise but no money.
Mr. Aune expressed his view that animal welfare organisations especially in Germany had enough money, which they could and should use to contribute to projects aimed at developing alternative methods.
Dr. Botham speaking on behalf of industry stressed that industry was committed to funding research into alternatives. But he also wanted to make clear that industry could only make money by selling safe products. In this regard it was absolutely mandatory that new alternative methods went hand in hand with obtaining the same or even better quality data to assess the risks of a product and to make the right judgements thereof. There was no point in trying to make industry invest in alternatives just for the sake of it, e.g. reducing the number of animal testing.
Dr. Garthoff also speaking on behalf of industry pointed out that industry was already quite involved in the funding of alternative methods citing the German foundation “set” as one example.
Mrs. Gabrielson felt that all parties concerned as well as the EU member states should contribute according to their means which was not only to be seen in the light of financial funding but of course also included it.
Finally, asked by Dr. Bansil about the flexibility of the proposed testing scheme, Dr. Vollmer replied that the system would be so flexible indeed, since it was not supposed to be a rigid but a living one. Dr. Walum also agreed that the system would be flexible enough to pick up new trends in science regarding alternative methods while Prof. Bolt also agreed in principle pointing to the level of interaction as a decisive factor in daily practice. Mrs. Gabrielson hinted that even though, according to the Commission, the new policy was no testing scheme, yet almost everyone throughout Europe had a quite different perception. She therefore stressed the need to find better ways of getting this message across.
Closing the panel discussion Dr. Bansil summarised that the dialogue had shown that all parties concerned were also mutually committed and had a role to play whether it would be financially, with science, with resource or with support. He added that there was scope in the future to bring more consideration of the 3Rs into the White Paper. In addition, there was a possibility to use other data such as human data but there was also a general agreement for a tiered strategy. It was also pointed out that there was a need for more education on alternatives as well as considerable funding for basic research and validation.
Moderators: Prof. P. Maier (CH) and Prof. J. Castell (E), ecopa-working group
Preparatory Session on the Founding of ecopa: Statutes, Proposals of Working Group
Prof. Castell commenced by explaining that a working group had been approved and installed after the first ecopa workshop in 2000 to develop ideas for launching ecopa as a non governmental organisation (NGO). This working group had met several times throughout the past twelve months discussing the different structures ecopa might have one day.
It was clear right from the beginning that ecopa would be a body that unified the different national consensus platforms but it was also agreed that there should be room for individuals and organisations that wished to participate. It was therefore not easy to draft a structure for an organisation that would enable platforms as well as individuals to take part.
The first question to be dealt with was regarding the best legal form for ecopa. It was discussed and concluded among the working group members that a non-profit organisation would be the best solution and it was also decided that it should be situated in Belgium and thus be organised in compliance with the Belgian laws. Then the statutes were drafted taking into account the input given by the participants of the first ecopa workshop as well as other experts in legal matters. This first draft was then circulated among the interested parties. Then replies had been received from various national platforms up to the beginning of this workshop. A new draft had been prepared incorporating the latest comments and suggestions, had been prepared and distributed prior to the start of this preparatory session.
It would be now up the national consensus platforms to discuss this draft and to agree on a final draft. This draft could be then reviewed by a lawyer to ensure compliance with Belgian laws before it would be submitted for publication in the “Moniteur Belge” marking the formal completion of the ecopa founding process. Prof. Castell pointed out, that agreement on this draft did not mean that the statutes would be fixed once and forever. Changes, amendments and additions would always be possible to accommodate needs that might arise over time when ecopa was a working and evolving organisation. But it was first necessary to agree on a basic set of rules that would serve as the basis for ecopa to work on.
He then explained that the draft statutes would be discussed section by section giving the attending participants the opportunity to voice any comments, remarks or suggestions before agreeing on that particular section and finally on the entire statutes. Afterwards the national consensus platforms willing to join ecopa would be asked to do so.
Regarding Article 4, Dr. Sauer referred to the sentence that ecopa may participate or become a member of other institutions and argued that this would cause problems and conflicts with the national representatives and/or bodies that were already members. She expressed her concern that if ecopa attended or joined other institutions such as the OECD or their expert groups then animal welfare organisations for example could be forced to withdraw to give space for ecopa.
Prof. Maier replied that Article 4 did not imply that ecopa had to join such bodies but only that it would have the option to join if such a situation arose and if such a step was deemed appropriate by the members. He also stressed that the intention of drafting these statutes was to provide for a legal structure that would be as flexible as possible foreseeing the needs of the future. Mrs. Gabrielson added that the decision to join or not to join would be taken on a case-to-case basis. If membership in another organisation indeed caused such problems then ecopa would evidently not join since the national consensus platforms would not accept it. In any case the board would have to consider all possible consequences before accepting or turning down an invitation to participate in or even join any other institution.
Prof. Thorn suggested changing the word order in the first and second sentence from “alternative methods (3-R-methods) to “3-R-methods (alternative methods)” since some scientists would disagree with the notion that alternative methods actually meant all the 3Rs, e.g. reduction, refinement and replacement. Prof. Maier illustrated that this was a difference between the English and German speaking countries and that he agreed with Prof. Thorn in changing the order of words to avoid any misunderstandings. Since there was no objection, this proposal was accepted and the draft statutes changed accordingly.
Also referring to Article 4, Dr. de Greeve suggested adding the words “and to enhance” to the very first sentence changing it to “The purposes of ecopa are to facilitate and to enhance the exchange”. No objections were voiced and the change thus agreed on.
Dr. Beaufays speaking on behalf of the Belgian platform referred back to Article 2 informing the participants that BPAM would be very happy to provide its office in Brussels to serve as the registered seat for ecopa. Concerning Article 4, he felt that the preference on replacement whenever possible should be mentioned clearly. Prof. Castell thanked Dr. Beaufays for the kind offer and explained that the final decision with respect to the organisation’s seat would have to be taken after the official constitution of ecopa. Regarding the notion of replacement, Prof. Castell replied that there would be a problem with emphasising one of the 3Rs due to the fact that there were about ten platforms, which had different opinions or preferences with respect to particular elements. Thus, it would be better not to highlight one of the 3Rs but to value them equally, especially since the adherence to all three elements of the 3-R-concept formed the common working basis for ecopa.
Continuing with Article 5, Dr. Sauer started out by illustrating what the German animal welfare federation in the German foundation “set” had said about the status of associate members. She said that if there were an ecopa then the basis for a trustworthy cooperation would have to exist right from the beginning. Regarding the membership criteria, the German animal welfare federation did not see a need for admitting any associate members if ecopa was to be a combination of European platforms. In this regard, she also argued that in the draft statutes it was foreseen that non-members of the national consensus platforms would also be able to take part in the executive committee thus exercising a considerable and unwarranted amount of power and influence. She therefore wanted the question of associate members to be reconsidered. Prof. Castell replied by explaining that a close look at the proposed structure showed that this was not the case since associate members would not have any voting power, which was exclusively the right of full members.
Dr. Smith asked about a clarification regarding terminology and whether or not there was a deliberate distinction between associate members as mentioned in the statutes and provisional members as written on a slide listing national consensus platforms for qualifying for membership. Prof. Maier replied that in the beginning it should not be a membership exclusion factor if a national consensus platform did not fulfil all criteria completely as outlined in the questionnaire. Yet, after a year the board should re-evaluate the situation to determine if these platforms had finally complied with all criteria and could thus stay a member or would have to become an associate member. In the meantime, the term provisional member would indicate that these national consensus platforms had not yet met all criteria though they were also founding members like those that had already fulfilled all criteria.
Regarding Article 10, Dr. Beaufays suggested to let the general assembly be attended by four representatives from each national consensus platform, e.g. one from each of the four parties concerned as an approach to strengthen the democracy and transparency even further. Prof. Rogiers replied that the working group had deliberately rejected this option on the ground that there should be one vote per platform and thus one representative voting on behalf of that particular platform. This was deemed sufficient since consensus actually meant that issues had first been discussed and decided at home. The representative would then be mandated and trusted to express the view of his or her platform regardless of his or her affiliation to one of the four parties back home. Needless to say that this did not imply that other members could not attend. Of course any member of a national consensus platform was welcome to attend a general assembly but there should only be one representative for each national consensus platform speaking with one voice and exercising one vote.
In addition, she stressed that this decision also had a quite practical reason. Due to geographic distances and the sometimes high travel costs it would be more difficult for some countries to send four representatives to Brussels than for others such as Belgium, Germany or the Netherlands. This would indeed create an unfair situation since some national consensus platforms could exercise their voting right with four votes while others would only have one or two.
Dr. Sauer said that if a trustworthy atmosphere were desired than this would require a balance between the four parties. Pointing to the situation in Germany, she added that there was even a balance between animal welfare on the one side and all other groups on the other side. As far as she was concerned she did not see such a balanced in the proposed structure of ecopa, which she felt would make a trustworthy cooperation impossible.
Dr. Garthoff stressed that the idea of a national consensus platform was that issues were being discussed and consensus decisions taken at the national level first so that the representative of a national consensus platform would express a common viewpoint. Thus, four votes were not needed since this person already spoke on behalf of all four parties. In the case that the parties could not agree on an issue nationally than their representative would not be able to vote on it at the ecopa level since there was no consensus decision found at the national level. He also added that ecopa was not the place for domestic problems to be discussed but to come forward with a common opinion.
Mrs. Gabrielson added that there would only be votes on issues at the general assembly that were on the agenda which was to be sent to the national consensus platforms three months in advance leaving plenty of time to discuss the issues and to decide on a vote.
Prof. Rogiers pointed to the nomination of two representatives of each platform explaining that this was done in order to make sure that there would always be at least one representative from each platform present at the meeting, e.g. to have a substitute in case of sickness and so on. But it was also intended to have some options with respect to the composition of the board to ensure that there would be equilibrium among the four parties. Therefore the call was made for the nomination of two persons from each platform, though only one would vote.
Dr. Boyd endorsed this view on consensus and explained that the discussion in the UK had led to the conclusion that the persons to be nominated should be the most knowledgeable and informed ones speaking on behalf of the entire platform regardless of their affiliation to one of the four parties.
Regarding Article 14, Dr. Sauer said that the difference between the board and the executive committee was not clear and that a board was actually not required according to Belgian law. Since ecopa was supposed to work in an unbureaucratic way, she therefore questioned the necessity for having both a board as well as an executive committee. Prof. Castell replied that though having both bodies was not required by Belgian law, it was deemed useful in a sense that for the daily work it would be better and easier to have a body comprising of 6 or 7 persons instead of one with 20, 30 or even more depending on the number of national consensus platforms joining over time. For practical reasons, it was thus decided to have a smaller sized executive committee in addition to the large board.
Dr. Schlitt, managing executive of the German foundation “set” referred to the 3-R-experts and asked if there was a necessity to furnish them with any voting rights. In the case of having 5 or 6 or more representatives from different platforms on the board, he did not see any need to give experts voting rights in order to balance the equilibrium since the representatives would suffice to reach such equilibrium.
Prof. Rogiers replied that the working group had already checked this on the basis of the nominations submitted by the national consensus platforms prior to this workshop. She explained that in effect there turned out to be an over-representation of science while animal welfare was under-represented. This actually led to the proposal to have the first three experts from animal welfare. In that case, of course, it would also be good if they had voting rights to exercise. In any case, the representatives from national consensus platforms would always outweigh the number of experts by two-thirds. Thus there was no risk of experts imposing any decisions on the actual members.
Dr. Greeve pointed out that experience in the near future would tell if voting rights for experts was necessary or not. Then the members could always decide and change the statutes to ensure a balance as well as an optimal working structure.
Regarding Article 17, Dr. Sauer repeated her already stated view during the discussion of Article 14 that there was no trustworthy cooperation possible as long as there would not be an equal representation on the board, e.g. one representative of each of the four parties from each national consensus platform. She also repeated her example of the German foundation “set” which according to her opinion was balanced since it made a distinction between those that were only interested in animal welfare and those that had additional concerns. Especially referring to Article 17, she strongly objected to the option of electing a president, vice-president or treasurer who was not a member of a national consensus platform.
Speaking on behalf of the German animal welfare federation she declared that on the basis of the current statutes this organisation had given the recommendation that the German foundation “set” should at this stage not participate in the founding of ecopa. She furthermore stated that the foundation of ecopa would cause serious problems if the animal welfare column did not feel adequately represented. The issue would therefore be reconsidered at the level of Eurogroup, the European Coalition as well as “set”. In addition, she declared that the German animal welfare federation was not willing to join ecopa.
However, Dr. Schlitt and Dr. Garthoff of the German foundation “set” explained that there had been a council meeting addressing this question and that a vote had been casted by the members of “set” by ballot with a clear majority in favour of joining ecopa.
Mrs. Gabrielson agreed with Dr. Sauer in principle but also said that one would have to face reality. It meant that there might be a situation where nobody representing a national consensus platform would be willing to serve as a president or vice-president due to the heavy workload that would go with such a function. It was therefore discussed and concluded that there should be an option to take non-members that were interested but even more also qualified and suitable for such a position. This was only an option for more flexibility but never to be misunderstanding as a must. In practice, of course, one would first try to fill these positions with people from national consensus platforms.
Dr. Garthoff added that for an organisation like ecopa to have greater impact it was important to be open to having a president that was a recognised person though he or she may not necessarily be a member of a national platform. Dr. Boyd said that in principle he would support the idea of a national consensus platform having four representatives but in practice this would actually not work.
Regarding Article 24, Dr. Sauer wondered if and how the secretary general should be paid since ecopa would not have any money in the beginning. She preferred the position to be a non-paid one but actually questioned the necessity of having a secretary general at all.
Prof. Castell mentioned that it was common practice to appoint a secretary general and it would be very difficult to find someone that would work for free since this position entailed a considerable workload as outlined in the statutes. He acknowledged that the budget would be rather small in the beginning thus providing very little opportunity for paying a secretary general or any other staff. Yet, it was a matter of flexibility and clarity to include this provision in the statutes, keeping in mind that needless to say any payment or reimbursement for a general secretary would have to take into consideration the budget that was available.
Mr. Potelle pointed out that Belgian law required a president, a treasurer and a secretary general, so there was no point in discussing whether a secretary general was wanted or not. He added that it was also stipulated that the vice-president or president could not fill that position but that it would have to be a different person. The internal regulations regarding Article 24 would thus have to be changed accordingly.
Concerning the budget, Dr. Sauer argued that apart Article 6 speaking of membership fees there was no mentioning of any other financial resources. Yet, the membership fees were and would remain too small to finance the basic expenses or even any special activities of ecopa. Prof. Rogiers and Dr. Garthoff explained that membership fees would never form a significant part of the budget but that sponsoring as well as contributions with respect to projects (EU and others) would have to be the major source of financing the operations of ecopa as shown by organising this workshop. This of course would be an evolving process. It was suggested and agreed to add a paragraph on the finances of ecopa that would address the question of acquiring and handling funds.
Rounding up this session Prof. Castell thanked everyone for their contributions and explained that the statutes would now be updated with the changes and additions discussed and agreed. A lawyer would then revise the draft to ensure compliance with Belgian law. Afterwards, the revised would be circulated among the national consensus platforms for final comments and then be sent to the “Moniteur Belge”.
Prof. Castell then asked the representatives of national consensus platforms that were willing to join ecopa on the basis of these statutes to come forward and to express their wish publicly.
The following representatives expressed their decision to join as full members:
|Prof. Dr. Pfaller||Austria||Under the condition that the statutes would be in compliance with Belgian law.|
|Dr. Beaufays||Belgium||Statement of the Belgian Platform to be taken into account.|
|Dr. Garthoff||Germany||German animal welfare federation expressed contempt.|
|Dr. de Greeve||The Netherlands|
|Prof. Dr. Castell||Spain|
|Prof. Dr. Maier||Switzerland|
|Dr. Boyd||United Kingdom|
The following representatives expressed their decision to join as associate members:
|Dr. Jírová||Czech Republic|
|Prof. Dr. Svendsen||Denmark|
|Prof. Dr. Smith||Norway|
|Prof. Dr. Wasowicz||Poland|
In addition, a list was circulated in which the representatives signed on behalf of their national consensus platforms documenting their decision to join ecopa. (The list forms part of these minutes and the statutes sent to the “Moniteur Belge”.)
Day 2, October 28, 2001
The discussion on the statutes had revealed that according to Belgian law it was impossible to elect the board members prior to the general assembly. Elections would have to take place at the general assembly, so in compliance with Belgian law the board elections were postponed to this end.
After the official launching of ecopa had taken place the day before, the workshop continued on Sunday with Prof. Rogiers informing the participants that Dr. Balls (ECVAM) had also been invited but that he could not attend due to timing problems. Furthermore he had stated that an ECVAM working group was currently preparing a report on the White Paper and that it would thus not be wise to attend a meeting having focus on this issue before the report was finished. He had therefore sent a letter, which he had asked Prof. Rogiers to read out to the participants (See Annex).
Citing the content of this letter, Prof. Rogiers said that ecopa experts would go to ECVAM to have a discussion about the paper currently being prepared by the ECVAM working group. In addition she added that there was already a draft of the mentioned report but that it would not be fair to circulate it at this workshop since this draft was not meant for distribution yet.
Dr. Garthoff added that in effect the visit and joint discussion would be one of the first actions to be taken up by ecopa. Prof. Rogiers agreed and explained that Dr. Balls had already reacted very positively when ecopa was mentioned for the first time during an ECVAM meeting. At this occasion Dr. Balls had stated that ecopa would be a good and effective partner to diffuse information, which was somehow problematic for ECVAM to do. She continued that the other present ESAC members had also expressed interest in ecopa and would regard it as a good way of information dissemination. In this regard, Dr. Garthoff added that ecopa could also serve as a platform for political statements that ECVAM as forming part of the Commission could and would never make.
It was thus concluded that ecopa would respond to Dr. Ball’s letter and accept his invitation for a meeting where ecopa would have a constructive and positive input by making concrete proposals.
Then Dr. Garthoff explained to the participants the basis on which the working group members had determined whether a national consensus platform qualified for ecopa membership or associate membership. He reminded the participants that a questionnaire on ecopa membership criteria had been circulated earlier this year asking interested national consensus platforms to fill in and return. Quite a number of national platforms replied with questionnaires being returned literally up to the last minute prior to the workshop. Based on the questionnaire as well as the replies the working group members evaluated each national consensus platform. Some platforms, such as the UK platform, turned out to meet all requirements right away while for other platforms one or more were not met.
The reasons for not meeting all criteria differed largely from platform to platform. In the case of Belgium there was a lack of information on the platform’s financial background while Finland, was currently reorganising its government-controlled platform into non-profit organisation. Norway, Sweden, and Denmark had bodies organised by government, which would be reorganised into full-fledged national consensus platforms in the following months. Spain was also reorganising its national consensus platform while Italy, the Czech Republic and Poland were in the process of forming such platforms.
Asked by Prof. Smith whether it was a problem if a national consensus platform was government appointed and financed, Dr. Garthoff replied this would indeed pose a problem if only one party appointed all the members of a platform. As far as financing was concerned it was acknowledged that it would be difficult to have a broader basis right from the beginning.
Regarding the ecopa working group, Dr. Garthoff suggested that it would carry on its work with the support of the members and associate members until ecopa was legally installed. The working group would thus in the meantime play a kind of godfather role for ecopa to follow up on the statutes all the way up to publication in the “Moniteur Belge” that would then mark the formal endpoint of establishing ecopa as a full-fledged international non-profit association according to Belgian law. There was no objection to this proposal and agreement expressed by acclamation.
The working group would furthermore see to it that the proceedings of this workshop were prepared, submitted to the participants for comments and finally distributed as well as published on the ecopa website. There was no objection to this proposal either.
The working group would take care of preparing the next meeting of the national consensus platforms before October 2002 as well as the general assembly combined with a workshop in October 2002. It was discussed and agreed that the next meeting could take place at the INVITOX conference in Italy and could actually be an official general assembly provided that all legal requirements were fulfilled with respect to the statutes and so on.
Splitting-up of participants in two groups to work on proposals for ecopa initiatives with guidance by Prof. Spielmann and Prof. Hendriksen
Both groups focused on three issues, which were presented afterwards:
- Chemical White Book,
- 6th Framework Programme as well as an
- Education and information programme on alternatives
Presentation of proposals by group 1
Dr. Bansil presented the results of Group 1 moderated by Prof. Spielmann. He illustrated that the chemical policy was discussed and agreed that the current policy did not work and needed to be changed. But although change was needed, there was a basic problem that the objective was to protect the environment but the focus was very much on human health. He argued that perhaps the objectives had been missed. Regardless of this people were still questioning what kind of information one wanted to get out of the chemicals policy.
The group agreed that focus was needed with respect to targeted risk assessment on the issues instead of simply generating large amounts of hazard data, which would require huge numbers of animals. This idea was brought up due to the fact that many people still regard the White Paper as a testing strategy and not as a data gathering exercise. It would appear to many people as a tick box-testing approach. It was also concluded that existing data should be used to avoid old tests being done over again with the same results but at the expense of animals.
However, the issue was not only testing according to new standards but in many cases there was a lack of technology to answer some of the questions that were posed. There was a strong feeling among the group members that if new technologies were needed to address the questions posed then one should try to develop in vitro methods first rather than more animal models. That would also help to change the mindset of many people who often perceived animal models as easier, cheaper and better to validate.
In the case of in vitro methods they would not only be used by the larger companies but also by many small and medium sized companies. These companies would need a reliable expert source of information on alternative methods since they were more likely to turn to an animal model right away due to a lack of information on other alternatives.
He further stated that the data on exposure should not be left out but used for risk assessment. In addition, one should use quantitative and qualitative structural activity relationships, e.g. by using existing data one should give strategies for everyone to use on risk assessment without animal testing. There should be a clear statement in the White Paper on how to get a derogation, e.g. how to avoid testing simply on the weight of existing data or on similar chemicals.
Furthermore, everyone agreed that a tiered testing structure was needed including a clear guidance on using all the available alternative methods first before resorting to animal testing.
Concerning research funding and referees it was concluded that referees were often a problem resulting in a lack of funding for alternative methods. The group had thus agreed that the selection of referees by free call for tender sending in applications was the best way to do but had proved to be troublesome. It once used to be that referees were selected by the member states without any additional quality control regarding the expertise and respective knowledge and understanding of the matter concerned. It was thus believed that the Commission should ask expert groups such as ecopa for nominees and ecopa in turn for instance would set up a data base with names of experts, the Commission could turn to. Groups like ecopa were suitable since they knew the people in the field.
It would also be very important to get experts to these discussions since in a group of ten people there may well only be one expert on in vitro methods. The generalists who did not fully understand the issue at hand would therefore quite often dilute this score. This was most likely one important reason why so many in vitro proposals had failed so far to receive funding.
It was also felt that in addition to an expert data base the Commission should look for focal points of expertise, for instance in vitro and biotech to make sure that there was a representative or a group of experts from that expert source to participate in all relevant screenings of applications. Experts on fisheries for example should not review applications for research in vitro methods for instance.
But the most important point with respect to in vitro was to earmark money for in vitro research. There was a need for an agreed sum of money set aside exclusively for basic research, screening and pre-validation. This way it could be assured that in vitro funding would not lose out to other more en vogue topics of the moment. Money would have to be put aside, so that in vitro applications would actually compete with in vitro applications but no others. In addition, there should be some criteria for the in vitro studies, which a group like ecopa could set the criteria by which in vitro projects could contribute to in vitro testing science.
Speaking of basic research, there was a basic feeling that a pooled sum of money for basic research to make sure that there would be coordination in the field. As far as money in general was concerned the group agreed that a lobbying document should be produced outlining the reasons for promoting further alternative methods in the EU, e.g. banning animal testing for cosmetics, developing an endocrine disrupters policy, the White Paper and so on. Such a document could be given to the national consensus platforms to lobby at the national level as well as lobby with the regulators at the EU level.
On education, the group stated that ecopa could play a valuable role with respect to educating young scientists for example. ecopa should come up with a lecture that could be used by all ecopa members at the European or national level, e.g. an ecopa endorsed lecture for university students on alternatives. It was furthermore agreed that there needed to be an ecopa website on a reliable server with links to the national consensus platforms and vice versa. But this also meant that someone would have to be responsible for the website and update it. It could either be the ecopa secretariat or one of the companies present at this workshop as one had already offered its resource and expertise to help upgrade and maintain the ecopa website.
Presentation of proposals by group 2
Dr. van der Valk assisted by Prof. Smith presented the results of Group 2. Regarding the White Book it was discussed to collect information on the implications on business, animal welfare etc. as well as other already existing statements in order to produce an own press release. This one could be used by the national consensus platforms at the national level but would also be communicated to the press and especially to scientific journals. National consensus platforms would play an important role due to their generally good contacts with local press.
Though the ecopa working group could start to prepare this press release with input from others, there was a need for an additional working group that would focus on the White Book.
Concerning the issue of alternatives methods, perhaps epidemiological studies could replace some of the testing of existing substances. The working group should discuss this in further detail. Concerning the issue of information the group acknowledged that there were problems with access to the companies’ data – even in the US where there is a Freedom of Information Act. It was concluded that data should be made available, so that one compound would not be tested several times.
An important first step would be to try to increase data sharing but at the same time respect industry’s investments and intellectual property. For future chemicals, post-marketing documentation (not mentioned in the White Book) could also be collected centrally.
With respect to additional funding, Dr. van der Valk illustrated that the White Book did not deal sufficiently with this problem. The cost-benefit conclusions were not good enough – and did not say enough about the cost of validating in vitro alternatives. In addition the group decided that there should be one central open list of funding possibilities for alternatives as an ECVAM workshop had already concluded in 1996! National representatives in the EC who were involved in the 6th framework should also be approached; so the EC made sure that there would be enough money to use predominantly for non-animal methods. A specific amount of money should be foreseen.
Regarding existing substances, the group had argued that there should be a push for a different approach. Delays should be proposed where necessary and ecopa should criticize the tight schedule and the rather rapid choice of experts.
Concerning the 6th Framework Programme it was discussed to collect names of those who were influential in putting the framework together. Furthermore, ecopa could comment on the 5th programme that it had only one program for alternatives that were funded and that the situation with respect to the 6th Framework Programme was even worse. It should highlight that there was still time to change the programme emphasising the need for funding and demanding the 20 million Euros as mentioned during the workshop.
In addition there should now be a focussed plea for alternatives in toxicology, but keeping in mind that toxicology would only account for 10% of animal use in Europe, i.e. this money should not be at the expense of funding other areas. Other areas of focus were for instance disease models or human cell culture methods.
Concerning animal experiments in basic research funded by the EC, the group felt that little consideration was given on how the 3 R’s were attended to here. More 3R expertise should thus be available and application forms should specify this. The explanatory booklet for the framework programme should also specify it. In addition, it was concluded that many of the experts were not alternatives experts. ecopa should therefore lobby to get such experts on the exam boards, for example by proposing particular experts. Ecopa should suggest and create a pool of experts nominated to the EC who would be used whenever 3R topics were discussed.
On education the group also decided that a training course for 3Rs should be established in close cooperation with the national consensus platforms since there was a general lack of information on alternatives available within this area. The ecopa website should contain a list of training courses in Europe.
Besides, the group felt that there was need to raise the status of alternative methods among scientists and to put emphasis on refinement in vivo tests. There should also be a European consensus on the accreditation of lab animal facilities to make sure the 3Rs would be attended to.
In addition, Dr. van der Valk continued that ecopa’s involvement in the harmonisation of education that it could be supportive of other organisations such as FELASA (Federation of European Laboratory Animal Science Associations) for example but it should not duplicate. The group thought that there was no consensus on what a practical and available alternative actually was and that a harmonisation in this regard was needed which ecopa could help to bring about.
Finally, concerning the ecopa website it was stressed that it would require a more reliable server with a more simple web address. The website should contain links to all the national platforms and vice versa as well as other relevant organisations, for example NORINA (Norwegian Inventory of Alternatives). It should also contain a list of ongoing projects and a list of funding organisations.
Taking up the amazingly similar suggestions made by both groups two new working groups were established. One group headed by Mrs. Gabrielson would focus on the issue of animal testing and the use of alternative methods with respect to the EC White Paper for a New EU Chemicals Policy. Volunteers for this working group were Prof. Pfaller, Dr. Kayser, Dr. Salmi, Dr. Weber and Prof. Spielmann.
The second group headed by Dr. van der Valk and assisted by Prof. Smith would concentrate on developing information and education programmes on alternative methods such as a lecture for university students as well as establishing the ecopa website as a main source of information on alternative methods. The national consensus platforms would be asked to suggest additional experts to serve on this working group. With reference to the ecopa website, it was also discussed and agreed to accept Dr. Bansil’s offer to receive expertise and support from P &G (Procter & Gamble). As far as finding a more reliable server was concerned, it was agreed, however, that it should be as neutral as possible to avoid any false conclusions about possible affiliations as a company server for instance might imply.
In addition, the already existing ecopa-working group headed by Prof. Rogiers would continue their work with respect to the 6th EU Framework Programme and aim to get 20 million EURO allotted exclusively for the development of alternative methods. Dr. Salmi and Dr. Bansil would join the working group in this regard.
Closing the workshop, Prof. Rogiers and Dr. Garthoff thanked everyone for their active participation and input. In addition, Dr. Garthoff referring to the next steps in the founding of ecopa explained that the revised statutes would be reviewed by a lawyer to ensure compliance with the Belgian law for international non-profit organisations before submitting them to the national consensus platforms once more. Within the next six months the final statutes should then be published in the Moniteur Belge, which would mark the formal completion of the ecopa founding process. In the meantime, the working group headed by Prof. Rogiers the general assembly as foreseen by the statutes and required by Belgian law. There would be a meeting before October 2002, possibly even as a general assembly in the full legal sense, as well as a general assembly combined with a workshop in October 2002.
END OF DOCUMENT (March 04,2002)