EU 6 th Framework Programme Project # LSSB-CT-2004-504776
THE IMPACT OF REACH
The report of the CONAM / ecopa Chemical Policy Working Group March 2007
“Copyright 2007 by ecopa (the European Consensus Platform for 3R -alternatives), resp. covered under the regulations of the EU 6 th Framework Programme-Reprint and reference consent to be obtained by the editors”.
Edition ecopa : Report 1, Brussels 2007.
Participants/Contributors : Tonia Devolder , BE Vera Rogiers, BE Bernward Garthoff, DE Horst Spielmann,DE Karsten Müller, DE Simon Webb, UK Marleen Pauwels, BE
Executive Summary
About ecopa and CONAM ecopa is the European Consensus Platform on 3R-Alternatives. It is an international not-for- profit organisation, officially established in April 2004 according to Belgian law. ecopa is the only quadripartite umbrella organisation at the European level concerned with the development and implementation of 3R-alternative methods to animal experimentation. The parties involved are Academia, Industry, Animal Welfare and Governmental Institutes. ecopa is a success thanks to the creation of so-called National Consensus Platforms (NCPs) in the different European Member States. Actually, 13 full member NCPs (Austria, Belgium, Czech Republic, Denmark, Finland, Germany, Hungary, Italy, The Netherlands, Spain, Sweden, Switzerland and the United Kingdom) and 3 associate members (NCPs under formation) exist (Ireland, Norway, and Poland). Recently, Norway and France officially finalised their consensus platform preparations.
As ecopa believes in international networking, exchange of information and good science as a solid basis for alternatives development, the CONAM (Consensus Networking on Alternative Methods within Europe)-project was initiated under FP6 (Project nr. LSSB-CT- 2004-504776), coordinated by ecopa 's chair Prof. Vera Rogiers. Major objectives consist of building new NCPs, creation of a newsletter ( ecopa messenger), website expansion, organisation of scientific workshops and meetings and stimulation of international cooperation.
These goals are accomplished by the activities organised within 4 workgroups, including a workgroup on political/scientific developments within REACH. The latter is at the origin of the in-depth analysis with respect to the impact of the REACH chemical legislation in the EU.
Within the CONAM-Project (EU 6 th FP, Project # 2004-504776), ecopa , its partners 1 and the stakeholder parties involved in the discussion around alternative testing to laboratory animal experiments, addressed the potential impact of the REACH chemical legislation in the EU on the future use of animals and the implementation of alternative methods and strategies. The impact was demonstrated, discussed and analyzed in several workshops and evaluated in a software tool “the ecopa REACH Animal Testing Calculator”.
For the future regulatory implementation on REACH and actual day-to-day practice of the legislation, the following key points and recommendations were identified by the WG:
• The REACH-legislation has changed and evolved over time since the publication of the original EU Chemical Policy White Paper. There is now a much more explicit role within REACH related to the use and promotion of alternative methods. • Based on the outcome of discussions amongst stakeholders at the different ecopa workshops and use of the downloadable ecopa REACH Animal Testing Calculator, the likely minimum number for laboratory animal use under REACH will be at least 6 million (but most likely significantly more, i.e. + 50 - 100%);
1 :The view of of Animal Welfare, represented by the ecopa board member Roman Kolar of Deutscher Tierschutzbund, is given at the end of this report, i.e. on page 60.
ecopa / CONAM report "The Impact of REACH", Mar 2007 1
• The major part (approx. 70%) of these animals will be employed during the testing phase <2014. • Animal use to address reproductive and developmental endpoints will account for >80% of overall animal use. This is significant as these are the endpoints likely to be most resistant to the successful development of replacements. • There is a clear mismatch between the likely development of alternatives (let alone acceptance by regulatory bodies) and the testing timetable of REACH. This is particularly striking, even if one assumes the most optimistic outcome of the FP6 projects addressing alternative testing. The implications of this have to be acknowledged by the Commission and national regulators and should be clearly communicated to the different stakeholders and the European public. • The results of the REACH Implementations Projects (RIPs) and the post-implementation behaviour of all stakeholders will be critical for the “animal testing need” of REACH. • In order to comply with the envisaged resource lack in the EU in regard to regulatory toxicology experts and study capacities, the Member States and the Commission will have an obligation to start not only immediate recruitment, but also initiate an obligatory training programme due to the complexity of REACH. • New alternative approaches should be considered by the REACH regulation as soon as they are validated and accepted by regulators. Each formal and informal method validation applies only to a limited set of test substances, the so-called “applicability domain”. The neglect of this consideration in the process of identifying “suitable” methods would be detrimental for the reputation of alternative methodologies. • While working together under the provisions of the REACH regulation, a certain level of mutual consent between industry and ECHA (European Ch emical Agency) and the competent authorities within the Member States has to be reached as soon as possible. Trust-building has to be facilitated. • The availability of testing resources and capacities (experts, labs, CROs), total number of substances and different chemical classes to be assessed, the outcome of socio- economic analyses etc. are outside the scope of this project. Nevertheless, they are likely to be significant determinants of the implementation of REACH and should not be ignored.. • Therefore, a clear definition, after carefully identifying, of those alternative methods acceptable to the regulatory communities and strategies (meant by “suitable" respectively "adequate” methods) is key in avoiding unnecessary testing on animals.
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Table of contents
1. Introduction...... 4 1.1 Development of REACH ...... 4 1.2 ecopa ’s Role...... 4 1.3 Creation of CONAM (6 th EU Framework Programme Project)...... 5 1.4 Intention of this Report...... 6
2. CONAM / ecopa -supported activities ...... 7 2.1 Animal Use under REACH and the ecopa REACH Animal Testing Calculator...... 7 2.2 CONAM / ecopa w orkshops...... 15 2.3 Conclusions, Propositions...... 23
3. Impact on and influence of relevant institutions...... 24 3.1 Competent Authorities of Member States ...... 24 3.2 EU Scientific Committees...... 24 3.3. "European Toxicologists" ...... 25 3.4 Contract Research Organisations...... 25 3.5 The Future European Chemical Agency...... 25 3.6 ReProTect Consortium...... 26 3.7 epaa ...... 26 3.8 Stakeholders ...... 26 3.9 Industry ...... 26 3.10 ECVAM (European Centre for the Validation of Alternative Methods)...... 27 3.11 ESAC (ECVAM Scientific Advisory Committee)...... 27
4. Summarizing Recommendations...... 28
5. Glossary ...... 31
6. References ...... 34
7. Appendices ...... 36 A. Templates for Assessment, Test Numbers of Studies B. Listing of Issues addressed in ecopa workshops on REACH and SCALE C. Short comment on the CONAM report “the impact of REACH”, March 2007 from an animal point of view by R. Kolar, ecopa Board Member, Deutscher Tierschutzbund
ecopa / CONAM report "The Impact of REACH", Mar 2007 3
1. Introduction
1.1 Development of REACH REACH was created by the European Commission in response to the concerns of European citizens, Member States and NGOs regarding the apparent lack of information on the safety of chemical substances available in the EU marketplace. The process was initiated by publication of The EU Chemical Policy White Paper in 2001 [COM(2001) 88 final] .
The White Paper was focused primarily on the likely procedures and processes to be adopted under implementation of REACH. However, it neglected the impact of REACH in respect to the potential cost of likely testing requirements in terms of both laboratory animal use and financial costs. Once this was recognized, the balance between laboratory animal use and the expected benefits within the European Union as regards worker, consumer and environmental safety subsequently became an important - if not central - element in the ensuing public debate over REACH. Much of this debate has been captured within contemporary editions of the ecopa “messenger” newsletter 2.
1.2 ecopa ’s Role The likely extent of the impact of REACH upon animal use was readily recognized by members of ecopa , who are drawn from the scientific, regulatory, industrial and animal welfare communities. Given the common and collective remit of the members, ecopa responded by initiating the following actions: - Establishing an online petition 3 based on a statement that was made available to the European public via the ecopa website; - Sending letters to appropriate Commissioners supported by the petition; - Organizing annual and specific workshops to provide fora for debate 4; - Alerting the Commissioner for Research (Phillipe Busquin in 2003) that the 6th Framework Programme of the EU did not envisage support for alternative method development necessary to address the needs of REACH and limit the impact of increased laboratory animal use. The Commissioner responded 5 and initiated inclusion of alternative methods within the 6 th FP.
2 Available through http://www. ecopa .eu/ under "Newsletter" (consulted 17 February 2007) 3 Available through http://www. ecopa .eu/ under "Archive/ ecopa news" ;" ecopa Statement in regard to the EU Chemical Policy" and "Statement of ecopa in regard to the EU 6 th Framework Program" (consulted 17 February 2007) 3 Available through http://www. ecopa .eu/ under "Archive/ ecopa workshops" ; see also 3 slides ‘REACH EU chemical policy under REACH chemical workshop ;" 4 Letter of Commissioner Philippe Busquin of July 28, 2003 to ecopa , available through http://www. ecopa .eu/ under "Archive/ ecopa news" .
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1.3 Creation of CONAM (6 th EU Framework Programme Project) A Specific Support Action (SSA) was initiated within the 6 th FP by ecopa and the Commission, called CONAM (Project # LSSB-CT-2004-504776 6). Within this project, ecopa members participated in cooperating and partnering in diverse other projects of FP6 such as ReProTect, Predictomics, ACuteTox, Sens-it-iv, Carcinogenomics 7 etc. and in further promoting the networking of the parties involved in alternative methods development from the scientific, regulatory, industrial, governmental and animal welfare communities. Furthermore, with the creation of an expert Working Group dedicated to Chemical Policy, CONAM served as a focal point for discussion around the impact that REACH was likely to have on animal testing and in the identification of priorities for the rapid development of alternatives to offset this impact. In order to alert governments and public to the evolving debate, CONAM supported by the ecopa -organisation and National Consensus Platforms provided regular reports via the ecopa “messenger” newsletter. Additionally, the Chemical Policy Working Group initiated the development of the “ ecopa REACH Animal Testing Calculator” that was made available for free download 8 . The potential of this tool in helping industry associations, companies, governments, animal welfare organizations, academia etc. to identify the impact of REACH in terms of animal use, has been broadly recognized and acknowledged 9,10,11,12,13 . Over the course of several workshops 14 , CONAM and/or ecopa provided fora in which to discuss REACH and address specific issues such as one substance/one test, data sharing, substitution, endocrine disrupter testing and the importance of reproductive toxicity testing as well as the likely lack of alternatives for this endpoint. Also of note is the inauguration of the European Partnership for Animal Alternatives ( epaa ) in November 2005. The aim of the Partnership is to facilitate cooperation between the European Commission and industry in the promotion of the development of alternative methods 15 . Most members of the CONAM Chemical Policy Working Group have taken an active role within the various structures and working groups of the Partnership.
6 More information through http://cordis.europa.eu/fetch?CALLER=FP6_PROJ&ACTION=D&DOC=1&CAT=PROJ&QUERY=1171726331 461&RCN=75331 (consulted 17 February 2007) 7 Available through http://www. ecopa .eu/ under "Archive/ ecopa news";"Contribution of ecopa in regard to the EU 6 th Framework Program" (consulted 17 February 2007) 8 ecopa REACH animal testing CALCULATOR for free download (2006), available through http://www. ecopa .eu/download.php?file=Animaluse_REACH_calculator.xls (consulted 17 February 2007) 9 Euro Voice for Animal Newsletter #13 available through www.eurogroup animal welfare.org/documents/pdf/issue13.pdf (consulted 23 February 2007); 10 ESTIV Newsletter #19 available through http://www.uta.fi/jarjestot/fincopa/ESTIV%20Newsletter%2019.pdf (consulted 23 February 2007); 11 NCA Newsletter #20 available through http://www.vet.uu.nl/viavet/userfiles/other/NCA_Newsletter_20_april_2006.pdf (consulted 23 February 2007); 12 P&G Forward Focus Newsletter Spring 2006 available through http://www.pg.com/science/PG_Q1_06.pdf (consulted 23 February 2007); 13 ECEAE Testing Times Newsletter #2 available through http://www.prijatelji-zivotinja.hr/pdf/testing_times_2.pdf (consulted 23 February 2007); 14 Details available through http://www. ecopa .eu/ under "Archive" - " ecopa workshops" 15 EPAA (the European Partnership for Alternative approaches to Animal testing); for more information, see http://ec.europa.eu/enterprise/epaa/index_en.htm (consulted 17 February 2007) ecopa / CONAM report "The Impact of REACH", Mar 2007 5
The overall evolution of REACH and related activities are depicted in Figure 1. REACH will be implemented in June 2007 and the European Chemical Agency (ECHA) will be officially established in June 2008.
Request for ecopa Alternative Alternative "Alternative on-line Research" in FP 6 petition Projects in FP6 Projects in FP7
Start Framework REACH Programme 6 Legislation
Foundation Foundation Foundation Chemical Directive ECHA Policy 86/609/EEC White Paper
1986 1991 2001 2002 2005 2006 2007 2008 2013 2018
Fig. 1: Time schedule of REACH events, connection to EU structures and Framework Programmes
1.4 Intention of this Report This report will highlight the accomplishments of the CONAM Chemical Policy Working Group. In particular, the outcome of the Stakeholder Workshop 16 held in 2006 and the learnings derived from application of the Calculator. Together these provide an insight into the likely impact of REACH upon laboratory animal use, as well as allowing the identification of actions that may potentially ameliorate and reduce this impact if implemented by the key actors.
16 REACH Chemical Workshop 2006: "REAlity CHeck: proposals, amendments and conclusions from the alternative point of view", available through http://www. ecopa .eu/ under "Archive", " ecopa workshops" ecopa / CONAM report "The Impact of REACH", Mar 2007 6
2. CONAM / ecopa -supported activities
2.1 Animal Use under REACH and the ecopa REACH Animal Testing Calculator Introduction The risk assessment principles of REACH are generally not different from the ones that are currently applied through existing chemical regulations [92/32/EEC, 99/45/EC]. Data are collected or generated de novo , hazards are identified and risks characterized. Substances are then managed on the basis of this assessment. What is different about REACH is the sheer scope and magnitude. Some 3,000 or so chemical substances have already been subject to regulatory evaluation of one form or another within the EU over the last 25 years. Under REACH over 30,000 substances will have to be studied and registered. REACH will also attempt to deal with this larger number of compounds within a shorter timeframe. It is as a result of this increased scope and consequent associated animal use that there is the current debate over REACH. Given that much has been said and written about likely animal use under REACH by the different stakeholders, the CONAM Chemical Working Group decided to try and develop a tool to estimate potential animal numbers in an objective and transparent manner. This tool would be made available to all parties to use with their own input parameters. The principle of the tool is simple and is based on a knowledge of test requirements under REACH, test protocols, the availability of existing test data and some estimate of the projected need to test for each endpoint under REACH.
Projected Animal use under REACH One of the first studies on projected animal testing requirements under REACH was conducted by the UK Institute of Environment and Health (IEH) [IEH 2001a] and estimated that 7.2 million animals would be required. This did not include pups associated with reproductive toxicity testing. These pups usually account for approx. 50% of the overall animal number (as can be derived by using the ecopa REACH Animal Testing Calculator). A second study from IEH [IEH 2001b] incorporated use of in vitro alternatives and estimated a markedly smaller figure of 1.2 million animals. In 2003 the European Commission provided an assessment of additional testing needs under REACH [Pedersen et al. 2003] . Whilst the focus was on the number of tests and likely implications vis-à-vis projected financial costs, the data included in the study (in terms of numbers of substances to be tested, potential data availability, application of read-across and QSARs, etc.) provided an initial framework which could likewise be employed to estimate animal use. An addendum to the initial report that attempted exactly this was subsequently published in November 2004 [Van der Jagt et al. 2004] . Two estimates of animal use were provided. A figure of 3.9 million additional animals “ as a consequence of the introduction of REACH if the use of alternative methods is not accepted by regulatory authorities ” and a second figure of 2.6 million animals that presumed considerable reduction in animal use based on the broad acceptance of alternative methods. Neither estimate enumerated pups associated with reproductive toxicity testing. The latter figure of 2.6 million corresponds to approximately 240,000 animals a year over the 11 year time period for the implementation of REACH. This was compared to an annual total of 9.8 million vertebrate animals [COM(2003) 19] used per year for experimental and other scientific purposes in the EU. The incremental increase in animal use was explicitly highlighted as an annual increase equivalent to 2 - 3%.
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Following the publication of the initial REACH proposal by the European Commission in September 2003 [COM(2003) 644] , Höfer et al. [2004] provided a comprehensive analysis of potential mammalian testing requirements. The intention was to provide an objective basis for a discussion on the needs for testing. When a consideration of reduction potential (based on the collective expert judgment of the BfR (Bundesinstitut für Risikobewertung, Berlin, DE) co-authors was taken into account the projected total use was 7.5 million animals, with approximately 80% of test animals being used in reproductive toxicology. For the purposes of comparison, the authors also highlighted that if no data were available and all endpoints were to be covered under REACH, total theoretical animal numbers would total 45 million. The latest assessment from the European Commission [JRC 2006] details an analysis based on the previous reports by Pedersen et al. [2003] and Van der Jagt et al. [2004] adapted to the Common Position of the Council [EC 2006/C 276 E/01, 2001] and reviewed with a specially constituted expert panel in July 2006. The number of pups from reproductive toxicity testing was considered in this latest assessment. The starting point was a theoretical maximum of 38 - 42 million animals. If existing data and exposure-based waiving were to be taken into account, this would be reduced to 23 million. “ Reasonable ” use of QSARs, read-across and grouping techniques in line with existing practices would result in a further reduction down to 18 million. Use of available alternative testing approaches would reduce this by a further 5 - 10 million animals down to 8 - 13 million. The estimated best case scenario was 8 - 9 million. However, there was an explicit caveat around this number due to the “ large ” uncertainty associated with the assumptions driving the calculation. This uncertainty is driven by assumptions regarding availability of existing toxicity data, acceptability of test waiving possibilities, potential realization of in silico and in vitro approaches and the impact of emerging technologies. “The general tendency in regulatory field (and in science) to ask for more studies and to make a firm statement on toxicity " was also highlighted. ecopa REACH Animal Testing Calculator The uncertainty over projected animal use associated with REACH is evident. Nevertheless, it should be understood that there is no one “right answer ”, as the output is highly dependent upon input assumptions. Given the importance of REACH, stakeholders collectively need a definitive and common evaluation of the potential impact. Different parties have promoted different numbers at different times for different purposes. This situation tends to complicate any objective debate between stakeholders in respect to the implications of REACH for animal use. What is required is means to evaluate use that is completely transparent with regard to the assumptions that drive the output so that it can be tested by stakeholders. Any global estimate is dependent upon a large number of underlying assumptions relating to factors such as the availability of existing data, the acceptability of methods, approaches and strategies that have the potential to reduce animal use and the likely behaviour of regulators etc. Estimates divorced from a detailed inventory of the underlying assumptions prohibit meaningful comparison. This tends to preclude consensus, which is one of the principle objectives of the CONAM project. CONAM therefore identified the need for a tool that would allow estimation of animal use with complete transparency of the underlying assumptions and initiated the production of the ecopa “REACH Animal Testing Calculator”. It is available as an Excel spreadsheet from the ecopa website. Since January 31, 2006: http://www.ecopa.eu/download.php?file=Animaluse_REACH_calculator.xls
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The calculator requires input information on: • The number of chemicals within each of the testing tiers within REACH; • The potential test requirements associated with each of those tiers; • Safety test method protocols (in terms of numbers of animals required); • The availability of existing data; • An estimate of likely testing need (which is a partial corollary of data availability, as well as the feasibility of the use of methods and approaches permitting a reduction in animal use). This information has been collated within the spreadsheet in a fashion that allows the Calculator to determine potential animal use for any given endpoint within a particular testing tier, as well as a global number for overall animal use. All sources are explicitly acknowledged within the spreadsheet. The Calculator has a user interface that explains operation of the spreadsheet, as well as providing the opportunity to modify all input values including substance number, test requirement, data availability and even animal number per test. This means that the tool can be used for sensitivity analysis as various scenarios are developed and tested. The tool also allows for graphical representation of the results. It is important to emphasize that the input assumptions employed when using the calculator are key to the output. Two baseline scenarios are included in the Calculator to assist the user and to be used as starting point for tailored modifications. One is based on available data where all the gaps are filled (available data need scenario, see Fig. 2a). A second scenario assumes that reduced testing is possible based on opportunities for read-across, grouping, QSAR etc. (see Fig.2b). Data availability and testing need for each endpoint within the default scenarios is taken from Pedersen et al. [2003] , which in turn are based upon data from the US EPA and ICCA HPV Programmes, IUCLID, VCI Voluntary Initiative (Germany) etc. In order to illustrate the output of the Calculator, projections from the more “ optimistic ” of the two default scenarios i.e., “ Reduced Data Need ” (Fig 3a) and of the more conservative “Available Data ” scenario (Fig 3b) are presented here. The results imply a total of 6.25 and 16.7 million animals respectively. The initial figure can probably be considered as a de minimis estimate. It is clear for this scenario that animal use is predominantly associated with REACH Annex X substances (i.e., >1,000 tonnes/annum). Whilst the absolute numbers may not be correct, the Calculator can clearly provide a rational basis to highlight areas that will most benefit from efforts to reduce overall animal use. For example, in the “ Reduced Data Need ” scenario, the overwhelming importance of the 2-generation reproductive study is very evident accounting for 71% of animal use. When all reproduction or developmental tests are considered together, this equates to >80% of animal use (see Fig.3a).
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(a) (b)
Reduced Data Need Scenario Available Data Scenario
Annex VII Annex VII 7% Annex X 5% 25%
Annex VIII Annex X 31% 47% Annex VIII 46%
Annex IX Annex IX 24% 15%
Fig. 2: Percentages of animal use allocated to the different REACH Annexes under (a) the Reduced Data Need Scenario or under (b) the Available Data Need Scenario Annex VII: standard information requirements for substances manufactured or imported in quantities of 1 tonne or more Annex VIII: standard information requirements for substances manufactured or imported in quantities of 10 tonnes or more Annex IX: standard information requirements for substances manufactured or imported in quantities of 100 tonnes or more Annex X: standard information requirements for substances manufactured or imported in quantities of 1000 tonnes or more
ecopa / CONAM report "The Impact of REACH", Mar 2007 10
Repro/Developmental Toxicity Screening in vivo Mutagenicity Sensitisation LLNA
Developmental Toxicity
Early Life Stage Fish Bioaccumulation Acute Inhalation Toxicity Carcinogenicity Repeated Dose 90d Repeated Dose 28d Repeated Dose 365d Other
2-Generation Reproductive Toxicity
Animal Use Reduced Data Need Scenario
Repeated Dose 365d
Repeated Dose 28d
Repeated Dose 90d
(a) Carcinogenicity
Acute Inhalation Toxicity
Bioaccumulation
Early Life Stage Fish
Developmental Toxicity
Sensitisation LLNA
in vivo Mutagenicity
Repro/Developmental Toxicity Screening
2-Generation Reproductive Toxicity
0 500,000 1,000,000 1,500,000 2,000,000 2,500,000 3,000,000 3,500,000 4,000,000 4,500,000 5,000,000
Sensitisation LLNA in vivo Mutagenicity Developmental Toxicity Repro/Developmental Toxicity Screening Early Life Stage Fish Bioaccumulation
Acute Inhalation Toxicity
Carcinogenicity
Repeated Dose 90d
Repeated Dose 28d
Repeated Dose 365d
Other
2-Generation Reproductive Toxicity Animal Use Available Data Need Scenario
Repeated Dose 365d
Repeated Dose 28d
Repeated Dose 90d
(b) Carcinogenicity
Acute Inhalation Toxicity
Bioaccumulation
Early Life Stage Fish
Developmental Toxicity
Sensitisation LLNA
in vivo Mutagenicity
Repro/Developmental Toxicity Screening
2-Generation Reproductive Toxicity
0 2,000,000 4,000,000 6,000,000 8,000,000 10,000,000 12,000,000 14,000,000 16,000,000 18,000,000 20,000,000
Fig. 3 : Distribution of overall animal use by study and endpoint under (a) the Reduced Data Need Scenario or (b) the Available Data Need Scenario
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A further interesting observation from the output of the Calculator, relates to the likely timing of animal test needs. REACH is envisaged such that higher tonnage materials are evaluated as a priority. When one considers likely REACH timings (see Fig.4), effective testing windows can be determined. For example, all data generation for Annex X substances needs to be conducted within 5.5 years of the start of REACH. Test windows for lower tonnage bands are longer. When considered collectively, this implies testing and animal use that is markedly skewed towards the early years of REACH (i.e., <2014). For the first 5.5 years of REACH, even under the most optimistic Reduced Data Need Scenario, annual animal use will amount to 788,000, falling to 249,000 for 4 years and then down to 153,000 for the remaining 6 years (see Fig.5). This can be compared to a current use of approximately 140,000 per annum for toxicological evaluations of compounds that would partly fall under REACH. The latter number represents an estimation based on statistics from the Member States ( 4th Report on Animal Numbers [COM(2005) 7] ), which by itself are generated under non-harmonized procedures and standards. In this context it is important to note that testing under REACH will not be exhaustive. Besides regular REACH-testing, there will also be a continued safety testing that accounts for assessing the relevance of toxicity mechanisms or for exposure-driven changes in the safety assessment strategy for existing chemicals. This will hold true during and in particular after REACH. REACH therefore represents a marked increase in animal use compared to the current baseline. Even if the absolute numbers are not correct, this skew will essentially remain unchanged. This is significant because the major part of testing needs are skewed towards 2009 – 2014 and related to those endpoints (i.e., reproductive toxicity) for which the availability of alternatives is least likely. The practical scope for any marked reduction in overall animal use via application of alternative methods or strategies is therefore constrained.
Mandatory Sharing of Vertebrate Data
>1-100t/y + Registration +11 Evaluation + 15 Testing Window 2024 Q2
Registration +6 Evaluation +9 >100-1000t/y Testing Window
Reg +3 >1000t/y Evaluation +5 + CMR 1&2 >1 t/y + R50/53 >100 t/y Testing Window
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Fig. 4 : Registration, evaluation and testing time frames for the different tonnage group chemicals.
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Annex VII, Annex VII, Annex VII & VIII 800,000 VIII, IX & X VIII & IX Reduced Data 700,000 Need Scenario 5.5 years 600,000 788,000 4 years Total 6.25 million per 249,000 500,000 6 years annum per 153,000 annum 400,000 per 300,000 annum
Animal Number per Annum Animal per Number 200,000 142,000 100,000 69% 16% 15%
2009 2014 2018 2024 Q2 Q2 Q2
Fig. 5 : Animal use per year in the reduced data need scenario compared to the baseline level of 142,000 animals for toxicological safety testing industry, household & cosmetics (according to the 4 th Report on Animal Numbers [COM(2005) 7] ). Annex VII: standard information requirements for substances manufactured or imported in quantities of 1 tonne or more Annex VIII: standard information requirements for substances manufactured or imported in quantities of 10 tonnes or more Annex IX: standard information requirements for substances manufactured or imported in quantities of 100 tonnes or more Annex X: standard information requirements for substances manufactured or imported in quantities of 1000 tonnes or more
CONAM reliability check of Available Data and Reduced Data Need Scenarios The publication of Pedersen et al. [2003] is a comprehensive and structured compilation and remains the definitive publication from the Commission on testing requirements under REACH. It provides the basis for the default assumptions employed in the Calculator. For this reason and in the absence of a more recent study by the Commission, an evaluation of the underlying assumptions as to their reliability and relevance was undertaken. This focused on: (i) the rationale in terms of plausibility and transparency regarding the information used to substantiate an assumption and (ii) the extent to which the supporting data is appropriate vis-à-vis extrapolation to REACH.
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Details of this evaluation are found in Appendix A. Data adequacy criteria were attributed to the different estimations through the following scores:
Score Criteria 1 "Specifically Relevant " Plausible description of rationale and methodology employed. Sources cited and readily accessible. Rationale based on empirical evaluation of a pre-existing data-set specifically relevant to the endpoint/species and the full range of substances (in terms of tonnages and chemical class etc.). Highest confidence in the adequacy of the parameter value.
2 "Partially Relevant " Plausible description of rationale and methodology employed. Rationale based on empirical evaluation of a pre-existing data-set partially relevant to the endpoint/species and/or the range of substances under consideration. Parameter value supplemented with expert judgement.
3 "Expert Judgement Alone " Parameter value based on expert judgement alone.
For example, a score of 1 (“ Specifically Relevant ”) is attributed to the estimation employed by Pedersen et al. (2003) for the likely availability of in vivo mutagenicity data for substances >1,000 tonnes/annum (Annex X). The figure of 38% employed to determine the “ Available Data ” scenario is based on the reported data availability from IUCLID for 2,465 EU HPVCs and is cited as coming from Allanou et al. (1999). This is clearly based on a pre-existing empirical data set specific for the endpoint and tonnage range that is explicitly cited and readily accessible. Accordingly, a score of 1 was applied. A score of 2 (“ Partially Relevant ”) is attributed to the estimation employed by Pedersen et al. (2003) for the likely availability of 2-generation reproductive toxicity data for substances >1,000 tonnes/annum (Annex X). The figure of 26% employed to determine the “ Available Data ” scenario is based on the reported data availability from IUCLID for “ toxicity to reproduction ” for 2,465 EU HPVCs and is cited as coming from Allanou et al. (1999). Given that “toxicity to reproduction ” relates to a broad set of reproductive endpoints and rather than exclusively to a 2-generation reproductive toxicity test, a score of 2 was applied – even though the tonnage range was relevant. A score of 3 (“ Expert Judgement Alone ”) was attributed to the estimation employed by Pedersen et al. (2003) for the likely availability of carcinogenicity data for substances >1,000 tonnes/annum (Annex X). The figure of 4% test need employed in the “ Reduced Data Need ” scenario is not substantiated in any way and was therefore characterised as having a score of 3. What is evident, is that whilst greater confidence can typically be associated with the assumptions employed for the highest tonnage tier (i.e., Annex X >1000 tonnes/annum), there is still a very large degree of uncertainty associated with the assumptions employed in the two default scenarios when taken as a whole. This particularly applies to the “ Reduced Data Need ” scenario. This should not be a surprise as the likely acceptability of QSARs, read-across and exposure-based waiving under REACH will be impossible to predict with a high degree of confidence, even by “ expert judgement ”. This is also explicitly acknowledged in the latest assessment based on the expert review [JRC 2006] .
ecopa / CONAM report "The Impact of REACH", Mar 2007 14
2.2 CONAM / ecopa w orkshops ecopa /CONAM organized a REACH Stakeholder meeting in February 2006 in Brussels, further referred to as "REAlity CHeck 17 ". This was in addition to several ecopa Annual Workshops that have likewise been devoted to the theme of REACH, most lately in November 2006. “REAlity CHeck” specifically focused on the impact of REACH in terms of the numbers of animal studies likely to be required under the new regulation and the overall number of animals that would be used in such tests. The input and views of all relevant stakeholders were actively solicited and presented in the workshop. A round table discussion also provided an opportunity for an interactive debate. All the presentations are summarized in Table 1 by mentioning the key points addressed by each of the speakers. Their full content can be viewed and downloaded through the ecopa website 18 . Estimates of animal use numbers associated with REACH from several authors and studies available at the time of the “REAlity CHeck” meeting were likewise summarized and provided on the ecopa -website 19 . Prior to the meeting it had become apparent that any assessment of the potential impact of REACH on animal use was likely to be subject to continuous change as a function of ongoing discussions within committee and plenary sessions of the European Parliament, between the services and agencies of the European Commission and at the Council. The “ ecopa REACH Animal Testing Calculator” proved to be a useful starting point for discussions in the workshop and as a tool to identify likely priorities for the development of alternatives. The calculator has subsequently also proved useful for education training courses and in substance portfolio planning studies within companies. The tool was further updated and presented at the 2006 ecopa Annual Meeting in November 2006 and helped to inform and stimulate a fruitful discussion. The estimates of likely final overall animal use under REACH as discussed at the 2006 Annual Workshop of ecopa have also been placed on the ecopa website 20 . At the same time, the JRC of the EU updated their view on impact figures [JRC 2006] . Since the November 2006 ecopa Annual Meeting also addressed the topic of REACH, the summarized presentations of the stakeholders presenting their views in that meeting have equally been taken up in this report. They can be found in Table 2.
17 REACH Chemical Workshop 2006: "REAlity CHeck: proposals, amendments and conclusions from the alternative point of view" 18 http://www. ecopa .eu/ under "Archive" - " ecopa workshops" 19 http://www. ecopa .eu/ under "Archive" - " ecopa workshops" 20 7th ecopa Annual Workshop 2006, available through http://www. ecopa .eu/ under "Archive" - " ecopa workshops" ecopa / CONAM report "The Impact of REACH", Mar 2007 15
Taking both 2006 meetings together, it becomes clear that all concerned parties were given the opportunity to express their views through individual presentations and round table discussions. The spectrum varied from: (i) Animal Welfare with contributions of Kirsty Reid and Ursula Sauer (Eurogroup) focusing on the proposed amendments that have not been included though continue to be requested, as well as on actions envisaged for the time when REACH comes into force (ii) Industry with representatives such as Gernot Klotz (Platform Sustainable Chemistry) with emphasis on achievements within REACH, Jean-Claude Lahaut (CEFIC & ICCA) with a focus on data sharing and Ian Ragan (Eli Lilly, EFPIA) exemplifying the IMI- initiative and the ICH-approach. (iii) In a round table session, a representative of an Environmental NGO , Ninja Reineke (WWF) was able to equally provide her view, while (iv) the likely perspectives of the academic community including the independent advisors of the EU Commission in the Scientific Committees were mirrored in remarks of Jim Bridges (University of Surrey, SCENIHR). (v) The potential of the epaa (European Partnership between Commission and Industries) to promote development of alternatives was addressed via a presentation and participation in a round table by Colin Humphries (CEFIC, epaa ), while some criticism was expressed the vis-à-vis the organization of the epaa with regards to insufficient participation of academia and national regulators from Hasso Seibert and Vera Rogiers.
Finally, the representatives of ecopa focused in their presentations on the “political” basis of REACH, how to achieve the "right" balance between environmental and animal welfare concerns and requirements, the feasibility of REACH regulations and implementation as well as potential contribution of the 5 th /6 th /7 th FP projects. ecopa addressed in several presentations the “political” issues (Bernward Garthoff, Vera Rogiers), but also in round tables (Odile de Silva) and covered the animal testing data issue in much detail (Karsten Müller, Simon Webb). It also presented ecopa ’s solution to the problems and its major contributions to the solution by assisting, partnering in and chairing a major part of the EU FP’s projects (José Castell, Vera Rogiers, and Bernward Garthoff). The potential of these projects, the fit respectively rather mismatch of the REACH timing scheme with these was identified and outlined in detail in these contributions.
All the above-mentioned presentations can be downloaded from the ecopa website 21 by clicking on the speakers' names.
21 Available through http://www. ecopa .eu/ under "Archive" - "CONAM WGII Report" ecopa / CONAM report "The Impact of REACH", Mar 2007 16
The major controversies identified during the many workshops organized around REACH are displayed in Figure 5:
Figure 5: Listing of areas of conflict, ethical issues, controversies between REACH actors.
For completeness, Appendix B offers an overview of all presentations addressed in ecopa workshops.
ecopa / CONAM report "The Impact of REACH", Mar 2007 17
Table 1: Overall listing of stakeholder comments during REAlity CHeck REACH Chemical Workshop, February 2006
Issue Stakeholder Group Author Key points addressing it "Current status of REACH DG Environment, Mark Blainey • current chemical management system inefficient legislation and European Commission • lack of stakeholder confidence in chemicals implementation" • need to balance protection health/environment versus protection laboratory animals "REACH - Outcome and Chair of SCENIHR, Jim Bridges • prioritisation based on tonnage does not fully implementation aspects" previously Chair of reflect risk CSTEE • alternatives not adequate for risk assessment • potential lack of availability of expertise in risk assessment • need for integration of learnings on an ongoing basis to improve risk assessment process, e.g. to improve ITS • rather neglected role of EU scientific committees "ICCA Global Policy - Basis" International Council of Jean-Claude Lahaut • experiences with and learnings from the ICCA Chemical Associations HPV initiative (CEFIC) • consideration of intellectual property with regard to data sharing • need to reduce ambiguities in language employed in the REACH text that may have legal implications • need to consider competitiveness and innovation under REACH "The Alternative Point of Eurogroup for Animal Kirsty Reid • importance of avoiding duplicating of testing and View" Welfare the obligation to share data • emphasis on development of testing strategies • hypothecation of testing fee for development of alternatives • the need for consultation of stakeholders during the evaluation of testing proposals
ecopa / CONAM report "The Impact of REACH", Mar 2007 18
Table 1 (cont'd) : Overall listing of stakeholder comments during REAlity CHeck REACH Chemical Workshop, February 2006
Issue Stakeholder Group Author Key points addressing it "What has been achieved EU Platform for Gernot Klotz • need for regulatory involvement in development under REACH?" Sustainable Chemistry and implementation of alternative testing strategies • need for REACH to address public trust issues • optimisation of resource use for ITS • need to share responsibility along the supply chain • decisions must be based on validated methods "ecopa REACH Animal Use ecopa Karsten Müller & • presentation of the ecopa calculator Calculator" Simon Webb • explanation of principles behind calculator • presentation of examples of projections "Societal Aspects of Institute for Public Law, Kurt Fassbender • consideration of societal dimension in REACH REACH and Alternatives to University of Bonn, debate Animal Experiments" Germany • need to recognize conflict between protection of human health and environment and protection of laboratory animals "Alternative methods Institute for Health and Thomas Hartung & • importance of ITS in terms of savings of animals already in existence for the Consumer Protection ECVAM Team and costs REACH implementation" (IHCP), Ispra (Va), Italy • need for a more coherent industry contribution • need to facilitate the validation process to meet the needs of REACH • role of evidence-based toxicology and potential limits of current animal studies • importance of focusing on reproductive toxicity
ecopa / CONAM report "The Impact of REACH", Mar 2007 19
Table 2: Overall listing of stakeholder comments during ecopa Annual Meeting, November 2006
Issue Stakeholder Group Author Key points addressing it "REACH and alternative DG ENTR Katinka van der Jagt • limitations of existing chemical legislation: data testing: the REACH gaps, unacceptable length of the process, need information requirements for shift of burden of proof and the perspectives to use • features of REACH: data sharing, authorisation, alternatives to animal burden of proof on industry, ... experimentation" • animal tests still needed as part of REACH • need to submit animal testing proposals in order to limit animal use • promotion of non-animal testing throughout REACH "Test Requirements of ecopa Bernward Garthoff • highlighting uncertainty around total animal use in REACH on the Long term REACH vs. Basis of New • need to balance protection of human health and Methodology" environment with protection of laboratory animals • need for constructive dialogue between stakeholders • current lack of availability of alternative methods/strategies • need for support for development of alternatives in future Framework Programmes "REACH & epaa : The way EU Commission, Christian Wimmer • importance of innovation, research and education to innovate by dual DG RTD in the EU partnership? The view from • presentation of the epaa the EU Commission." • Framework Programme 6 and 7 instruments and budgets for alternative methods • introduction of different EU platforms dealing with alternative methods • development of alternative methods via the 5 th and 6th Framework Programmes and its partner projects
ecopa / CONAM report "The Impact of REACH", Mar 2007 20
Table 2 (cont'd) : Overall listing of stakeholder comments during ecopa Annual Meeting, November 2006
Issue Stakeholder Group Author Key points addressing it "REACH & epaa : The way epaa Colin Humphris • complexity of REACH vis-à-vis animal testing to innovate by dual CEFIC • potential role of epaa to address regulatory toxicity partnership? The view from needs industry" • potential of cooperation between industry and with the Commission to achieve progress "REACH and epaa : the way University Medical Hasso Seibert • necessity of more intense academic contribution in to innovate by dual School Schleswig- the development of alternatives Partnership? The view from Holstein, Germany • potential limitations of in vitro methods and outside: Academia" extrapolation to in vivo conditions • limitations of single in vitro systems "Impact of REACH on ecopa Simon Webb • increased scope and magnitude of animal testing Animal Use" under REACH driving the debate; de minimis use of animals under REACH > 6 million • presentation of updated version of the calculator • how input assumptions drive animal use and the importance of reproduction toxicity • mismatch of timing of testing needs and likely availability of alternatives • influence of behaviour of key actors in REACH implementation upon ultimate animal use "REACH and current Institute for Health and Thomas Hartung & • importance of focusing on reproductive toxicity alternative methodological Consumer Protection ECVAM Team • potential of modular approach for validation approaches in (IHCP), Ispra (Va), Italy • potential of Framework Programme 6 projects to (pre)validation" deliver alternatives • importance of ITS and RIPs to reduce overall animal numbers
ecopa / CONAM report "The Impact of REACH", Mar 2007 21
Table 2 (cont'd) : Overall listing of stakeholder comments during ecopa Annual Meeting, November 2006
Issue Stakeholder Group Author Key points addressing it "Outcome of the 6 th FP ecopa Vera Rogiers • feasibility and realistic timing of delivery of Projects, help for REACH?" Framework Programme 6 projects on alternatives • timeline and magnitude of animal testing needs under REACH • mismatch of delivery of Framework Programme 6 project results and the needs of REACH "The Innovative Medicines Eli Lilly and EFPIA Ian Ragan • experiences with the 3Rs in pharmaceutical Initiative: Implications for development the Development of 3R- • potential of genomics and biomarkers Alternatives" • concerns over safety and efficacy failure of animal studies to predict effect in man and the implications for clinical development • importance of data sharing under the Innovative Medicines Initiative "Expectations from animal Eurogroup Ursula Sauer • need for concrete provisions to promote the welfare" development and acceptance of non-animal tests • need for mandatory rules to make available and share existing data • need for evaluation of all testing proposals • need for replacement of animal test methods by non-animal testing
ecopa / CONAM report "The Impact of REACH", Mar 2007 22
2.3 Conclusions There are some clear conclusions that can be readily drawn as a consequence of the insights provided by the activities organized under the aegis of CONAM: • There is no generally accepted interpretation of the need for safety testing for the diverse endpoints. Opinions will differ amongst the various actors on the need for testing, the scope for exposure-based waving, use of QSAR and interpretation of other supporting data. This creates a high overall level of uncertainty around the likely impact of REACH on global animal use; • Based on the outcome of discussions amongst stakeholders at the workshops and use of the ecopa Calculator, the likely minimum number for laboratory animal use under REACH will be at least 6 million (and most likely significantly more i.e.,+ 50 - 100%). Moreover, in all calculation scenarios, the numbers of animals needed for carcinogenicity, developmental neurotoxicity, endocrine disrupter testing etc. have not been included. They will, however, be considered by the regulatory authorities on a case by case basis. For all these endpoints, no validated alternatives are available. • The major part (approx. 70%) of these animals will be employed before <2014. This may be the case because under “real life” working conditions, companies will be inclined to initiate testing earlier in order to avoid any delays or complications in the registration process. However, the time-consuming consultation of stakeholders is opponent to this; • Animal use to address reproductive and developmental endpoints will account for >80% of overall animal use. This is significant as these are the endpoints likely to be most resistant to the successful development of replacements; • The outcome of the 6 th Framework Programme Projects intended to support the replacement and overall reduction of animal testing were judged unlikely to be available in time to significantly impact animal use during the early stages of REACH (even assuming complete success). Nevertheless, they may still be helpful in the later stages; • There is a clear mismatch between the likely development of alternatives (let alone acceptance by regulatory bodies) and the testing timetable of REACH. The implications of this need to be acknowledged by the Commission and national regulators and clearly communicated to stakeholders; • In addition to communication, concrete measures are required to address this mismatch. Immediate additional research to balance the situation is needed. And reduction in funds for alternative test method development under the 7th Framework Programme will not be accepted by stakeholders; • The inauguration of the epaa and resulting activities may have some impact on overall animal use. This will need to be evaluated on an ongoing basis. • The results of the REACH Implementations Projects (RIPs) and the post-implementation behaviour of all stakeholders will be critical for the animal need of REACH.
ecopa / CONAM report "The Impact of REACH", Mar 2007 23
3. Impact on and influence of relevant institutions
An additional remaining uncertainty is the post-implementation behaviour of the major actors and this will consequently be critical in determining the final actual overall impact of REACH. Several institutions will affect the way in which REACH will be implemented in practice, some are considered below.
3.1 Competent Authorities of Member States Actual animal use will be highly dependent upon the interpretation of test needs by regulators. There is a concern amongst some parties that the behaviour of regulatory authorities is often predisposed towards increasing animal use under REACH. Regulators are vested with the responsibility to ensure human and environmental safety. As such, their interpretations of data needs and safety assessments are often perceived as favouring a degree of caution. Experiences with SPORT (Strategic Partnership on REACH Testing) 22 have demonstrated that many cases of “ non-compliance ” resulted from non-acceptance by Member States Competent Authorities of waiving or grouping arguments put forward by industry. If this apparent lack of mutual understanding concerning the interpretation of the requirements is replicated following the implementation of REACH, this would tend to increase animal use. Such observations have led to dialogue about the need for ” intelligent testing strategies ” (ITS) and the need to avoid “ overly conservative ” or “ tick-box ” approaches. To some extent, changes in the behaviour of regulatory authorities are therefore implicit in any expectations around ITS. But this will require “ buy-in ” from regulatory authorities, something that perhaps is best achieved by their participation in the development of ITS. Attitudes may well evolve over time with the increasing experiences in the day-to-day implementation of REACH. An ever expanding database will likely increase comfort and permit acceptance of arguments and approaches aimed at limiting animal use. Familiarity with new methods - including in-vitro derived data - will likewise increase with time. Time gets short, because, as pointed out above, most animals will be needed in the initial period.
3.2 EU Scientific Committees The SCCP, SCHER and SCENIHR (or their antecedent bodies) have often been called upon to advise on the applicability of alternative methods to animal testing in relation to safety assessment. These committees have often identified limitations and this may have been interpreted by some stakeholders as reflecting opposition to the implementation of alternatives to animal experimentation as a matter of principle. The Inter Committee Coordination Group of Scientific Committees (ICCG) has published a position statement that refutes such an interpretation and maintains that any critical concerns of the Scientific Committees on the validity of 3R alternatives are not based on any inherent opposition to alternatives per se [ICCG/1/06] . On the contrary, they agreed that the ongoing development and validation of alternatives is to be encouraged. Nevertheless, the future stance of the various Scientific Committees on acceptability (or otherwise) of individual alternative methods and approaches undoubtedly has the potential to impact overall animal use under REACH.
22 See http://www.sport-project.info/report.htm (Consulted 17 February 2007) ecopa / CONAM report "The Impact of REACH", Mar 2007 24
3.3. "European Toxicologists" In October 2005, a group of senior European toxicologists publicly expressed their reservations about potential provisions within REACH that would diminish reliance on in vivo studies in favour of non-animal methods based on considerations of cost reduction and protection of animals rather than protection of human health and the environment [Greim et al. 2006]. Their prime concern related to repeated dose studies and the inability to identify thresholds of effects and NO(A)ELs essential for risk characterisation via in vitro studies. They were explicitly concerned that the debate around REACH was increasingly centered on ways in which well-established in vivo methods for risk assessment could be by-passed. They additionally highlighted their belief that evidence that available alternatives could support such replacement was weak and that exaggerated claims for progress in alternatives is damaging their development. It is self-evident that the confidence of the European academic, regulatory and industrial toxicologist in alternative methods will impact overall animal use. Further, the short REACH deadlines urge all actors to get more toxicologists engaged than available. The degree of toxicological education is critical for proper safety assessments and points out to the necessity of training courses for safety assessors. The potential use of alternative methods, with their strengths and weaknesses, must be explained in relation to the complexity of the different annexes to REACH.
3.4 Contract Research Organisations The implementation of REACH will entail a marked increase in animal use. As a consequence the availability of testing capacity with industrial laboratories or contract research organisations (CRO's) needs to be understood. The number of animal studies required under the Reduced Data Need (RDN) scenario is >33,000. Given the substantial uncertainties associated with this scenario, this may well be an underestimate. Of these >33,000 studies, over 2,000 would be 2-generation reproductive toxicity studies. This study is particularly resource intensive in terms of time, cost, human capital and animal use. The number of such studies conducted in recent decades is probably of the order of 200. As such, a projected total of >2,000 is somewhat likely to be infeasible from a simple test logistics perspective. In a similar fashion it has also been suggested that “ availability of (an) appropriate number of laboratories being skilled in alternative testing ” might also be problematic [JRC 2006]. Test capacity and/or expertise may well come to constitute a barrier to the effective implementation of REACH.
3.5 The Future European Chemical Agency At Community level, a European Chemicals Agency (ECHA) for managing the technical and administrative aspects of the REACH system in a harmonised fashion is created. Work is underway to establish this central co-ordinating body which will be based in Helsinki, Finland. ECHA will scrutinise all testing proposals submitted with a registration dossier, with the duty to ensure no unnecessary animal testing is carried out. Additional testing may also be requested on the basis of national authorities' evaluation. Practices and interpretation on the part of ECHA will therefore have a central role in determining the number of animals used under REACH.
ecopa / CONAM report "The Impact of REACH", Mar 2007 25
3.6 ReProTect Consortium Amongst toxicity testing under REACH, reproductive toxicity has the highest impact on the number of animals used for safety assessment. According to the ecopa “REACH Animal Use Calculator”, approximately 80% of all animals in the safety testing of chemicals will be used to assess whether a substance is affecting fertility of females and males or development of embryo, fetus and offspring. To accomplish this, a broad variety of individual parameters have to be investigated. Animal studies cover the complexity, but non-animal methods are inevitably split up into separate assessment of parameters like e.g. spermatogenesis, folliculogenesis, nidation, organogenesis, and lactation. The EU funded integrated project ReProTect (IP 503257) 23 is following these lines and represents the biggest programme in this area. The work of the 35 partners -including ecopa - started in 2004 and will run until 2009. Most parameters are in a R&D stage and will have to be fed into the validation process. The validation of every single assessment of a reproductive process as well as validation of the overall testing strategy will potentially take upwards of 5 years, i.e. year 2014. Obviously, the weakness of splitting reproduction to single processes is that every process will have to be validated successfully to make the strategy workable. Each failure places in doubt the overall objective of an integrated battery of in vitro based testing of reproduction.
3.7 epaa The overall objective of the epaa is to promote the development, validation and acceptance of alternative methods. Separate working groups are devoted to speeding up the validation process, identifying research priorities, optimising interpretation of regulation, dissemination of best practice and making up an inventory of industry use of alternatives. If successful in its objective, the epaa may impact animal use under REACH.
3.8 Stakeholders Some further issues will result from the potential to delay testing proposals submitted to the authorities during the proposed comment or consultation period. This will give ample opportunities to stakeholders to attempt to influence the testing process for individual compounds. Inputs on many – if not all - test proposals are likely from different parties on different grounds. Some will call for more testing, others will question the need for any testing at all. Overall this will potentially delay the processing of testing proposals as resources (which are finite) will have to be dedicated to address stakeholder inputs.
3.9 Industry REACH foresees that only 5% of submitted dossiers will be evaluated by the ECHA. The burden of proof for the risk assessment of chemicals will more than ever be placed on industry. This may tend to influence the approach adopted within industry. There may be a tendency for some parties in some situations to propose more comprehensive testing than necessary to demonstrate safety. This may be for reasons of expediency in order to avoid any potential delays or hightened caution due to the shifted burden of proof.
23 See http:// www.reprotect.eu (Consulted 17 February 2007) ecopa / CONAM report "The Impact of REACH", Mar 2007 26
3.10 ECVAM ( European Centre for the Validation of Alternative Methods ) ECVAM was created in 1991 as a part of DG JRC through Directive 86/609/EEC with the task to validate novel alternative methods to animal testing. In this regard it supported the 6 th FP projects directed to the REACH legislation. During the REACH legislative process, ECVAM assumed the additional role of bringing in "suitable methods" in addition of validated methods.
3.11 ESAC (ECVAM Scientific Advisory Committee) ESAC consists of scientific experts and representatives out of the European Community, Member States, trade associations and NGOs. The role of ESAC is to ensure that alternative methods are based on robust science and ready to be recommended to regulators worldwide once validated. Therefore, in the future discussions, ESAC as well as its supporting experts, including those of ecopa , have a very important role to play in the current REACH implementation phase and later stages.
ecopa / CONAM report "The Impact of REACH", Mar 2007 27
4. Summarizing Recommendations
On the current basis of the REACH legislation [EC 1907/2006/EC, 2006] and REACH implementation projects (RIPs) 24 (as of end of 2006), the following observations and recommendations have beeen made by the CONAM Working Group: • The REACH-legislation has changed and evolved over time since the publication of the original Chemicals Policy White Paper. There is now a much more explicit role within REACH related to the use and promotion of alternative methods. • The manner in which the Member States - especially their authorities - and the new European Chemicals Agency (ECHA) will deal with the registration documents and testing proposals submitted by industy will be critically important. To that end, it is recommended to have an advisory committee of scientists in place reviewing in a neutral and objective manner the decisions of ECHA and national authorities. This should especially be the case in regard to requests for additional testing, in particular regarding additional laboratory animal testing studies. • In order to comply with an envisaged resource lack in the EU, the Member States and the Commission will be obliged to start an immediate recruitment and training programme for toxicologists. Additional toxicology curricula, student recruitment (even from abroad outside EU) and training courses for further development in areas such as in vivo regulatory toxicology, alternative method R&D and validation, chemical knowledge including QSAR-methodology and reliability of it and other topics have to be pursued. • It is essential that the Executive Director of the ECHA to be appointed by June 1, 2007 has knowledge in regulatory toxicology, in chemical testing, laboratory animal testing and above all alternative method development (3 Rs) as well as a strong scientific background. Similarly, this should also be required from her/his staff, especially from the evaluating toxicologists in order to have quality assessments and reduced animal study requests. Industry has to submit testing proposals to ECHA. It depends on the toxicological experience within ECHA to have a proper assessment and evaluation of the necessity to perform higher tier and animal consuming tests. Stakeholders and Member State authorities may use a time period designated for comments. In contrast to substance evaluation, it is a primary task for ECHA to evaluate testing proposals. Unfortunately, there are yet no official flow charts available that can illustrate the processes behind Articles 40, 41 and 51 of the final REACH text of Dec 18 th , 2006 [EC 1907/2006/EC], at least not by the time this report was edited. • New alternative approaches should be considered by the REACH regulation as soon as they are validated and accepted by regulators.
24 For more detail on REACH Implementation Projects, see http://ecb.jrc.it/reach/rip/ (Consulted 17 February 2007) ecopa / CONAM report "The Impact of REACH", Mar 2007 28
• The approach of potentially reducing the test numbers by applying “suitable methods” based on screening methodology used in industries, bears some risk, i.e., - creating second class testing documents submitted to agencies (“alternative documents”); - diminishing the “trust” of authorities inside and outside of the EU in results and test methods designated as “alternatives”; - making it even more costly for companies, since they might additionally be asked to perform in vivo -studies on top. This would be even harmful for winning acceptance of alternative methodologies; - expanding the use of a specific alternative test to chemical structures, where the predictive value and reliability are insufficient (i.e., outside the applicability domain). Each formal and informal method validation applies only to a limited set of test substances, the so-called applicability domain. The negligence of this parameter in the process of identifying a “suitable” method would be detrimental for the reputation of screening methodologies. The applicability of test methods already used in industries, but not necessarily fully validated, is currently under evaluation in one of the Working Groups of the epaa . These methods, most of them developed for screening purposes, are certainly valid for their initially intended application, but claims regarding their usefulness for registration purposes - including REACH applications – must be considered carefully.. On the other hand, screening tests have been proven to provide useful information, often sufficient for internal decision-making processes, and, when combined with additional available information, sometimes even decisive for selected endpoints. This holds true for special cases where the strengths and weaknesses of the test method as well as the applicability domain have been thoroughly assessed. Unfortunately, experience and ongoing discussions in the RIPs indicate that negative results (i.e. results indicating the absence of a dangerous property) of such screening tests are rarely accepted by regulatory authorities.The substance may still be classified out of precaution or the corresponding animal test may still be demanded. Although it is acknowledged that screening studies alone might not generate the required level of information for a final hazard assessment, ecopa advises against discouraging them on the sole basis of distrust. Combined with other test results from well-performed studies, screening studies may in some cases give a robust and sufficient indication that classification is not required. In the light of reducing animal numbers, this should be considered. • There is a perception amongst certain parties that ECVAM and the Commission tend to overlook some of the the concerns of the regulatory agencies and the Commission’s own toxicological experts regarding the validation and/or acceptability of alternatives for safety assessment. In the past, independent toxicology experts advising the Commission have addressed the issue of acceptability of alternative methods in 3 documents [CSTEE 2004, SCCNFP/0834/04, ICCG/1/06, Greim et al. 2006].
• The premature support for non-validated methods might sometimes be even contra- productive. If authorities turn down in dossiers submitted for REACH or other submissions on this basis, “trust” is lost and unfortunate precedents are set. In that context, it was interesting to note that during the first annual meeting of the epaa- Partnership in December 2006 in Brussels, representatives of EMEA (the European Medicines Agency) used the word “trust” when commenting on the process that will determine whether their agency will be induce to make decisions based on alternatives i.e., “whether we will accept an alternative, depends on whether we can trust the results, and the method used for it. ” Until now, the “trustfulness” of a method as an alternative test to animal experiments is dependent upon ESAC, a scientific evaluating committee of Member States representatives and those of relevant associations and NGOs (including ecopa ). If that is to be changed, then the Commission will have to make an official ecopa / CONAM report "The Impact of REACH", Mar 2007 29
announcement via the Chemical Agency. The recent example of a politically and economically driven recommendation (by ECVAM by-passing ESAC) for a test system proposed by a German SME, does not support the concept of “trust”, required by regulatory authorities. • Above all, the issue of reproduction toxicology has to be addressed in much more comprehensive fashion, preferably involving all the regulatory authorities. Most studies on reproductive toxicity will be demanded by REACH for substances produced or imported above 1000 tonnes per year and 100 - 1000 tonnes per year. The corresponding registration phases and the proposals for tests will run until November 30th, 2008 and May 31st, 2013, respectively. As indicated previously, replacement in vitro alternatives will certainly be too late. Reproduction toxicology studies will account for approximately 70% of animal testing needs under REACH. A partial solution has been identified that aims to limit testing to a “one”, or “one and a half” – generation study. The savings in animal numbers would be substantial, but the acceptance in the regulatory (and therefore, industrial world) may well be low given the current state of knowledge. A small group of major companies (working under the aegis of the epaa and in conjunction with ECVAM) is currently trying to validate the extended protocol of the 1- generation reproduction study and to implement a tailored testing regime.
• The methods that have been or will be developed may be of importance to elucidate the mechanisms of toxicity or to assist in choosing one out of several related substance candidates with identical mechanism (screening or optimization purposes). Hence, their role will also be to assist in intelligent testing strategies (ITS) that are designed to reduce animal testing. Given the timeframe, ITS will be of more influence on animal numbers than direct replacement methods and should be implemented consistently. REACH explicitly introduces waiving criteria that can be targeted. However, all such methods mentioned above have already been considered in the ecopa animal use calculator in the “ Reduced data need ” scenario. • While working together under the provisions of the REACH regulation, a certain level of mutual consent between industry and ECHA and the competent authorities within the Member States has to be reached as soon as possible. If this is not achieved, industry will perform more testing to satisfy presumably conservative regulators and conversely regulators will tend to ask for more tests from industry that they consider as trying to manage with less. Consent and trust will be a powerful measure to reduce animal numbers required for safety testing. Openness and personal contact will be a prerequisite for a fruitful collaboration. Considering the number of chemicals that are currently assessed by authorities and industry (e.g., 120 new chemicals across Europe per year), this may well not be practicably achievable under REACH. • The availability of testing resources and capacities (experts, labs, CROs), total number of substances and different chemical classes to be assessed, the outcome of socio- economic analyses etc., have been highlighted, but not fully evaluated in this study.
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5. Glossary
3R Refinement, Reduction, Replacement Alternative methods All those procedures which can completely replace the need for animal experiments, which can reduce the number of animals required, or which can reduce the amount of pain and stress to which the animal is subjected in order to meet the essential needs of humans and other animals CEFIC European Chemical Industry Council CMR Carcinogenic, Mutagenic, toxic to Reproduction CONAM COnsensus Networking on Alternative Methods CRO Contract Research Organisation CSTEE Scientific Committee on Toxicity, Ecotoxicity and the Environment DG Directorate-General DG ENTR Directorate-General Enterprise DG RTD Director General for Research EC European Community ECB European Chemicals Bureau ECHA European CHemicals Agency ecopa European Consensus Platform on 3R-Alternatives ECVAM European Centre for the Validation of Alternative Methods EEC European Economic Community EFPIA European Federation of Pharmaceutical Industries Associations EMEA European MEdicines Agency EP European Parliament epaa European Partnership for Alternative approaches to Animal testing ESAC ECVAM Scientific Advisory Committee EU European Union Fig. Figure FP Framework Programme HPV(C) High Production Volume (Chemical) ICCA International Council of Chemical Associations ICCG Inter-Committee Coordination Group IEH Institute of Environment and Health IHCP Institute for Health and Consumer Protection
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In silico test method Method making use of a computer or a computer simulation on the basis of existing related data In vitro test method Biological method : using organs, tissue sections and tissue cultures, isolated cells and their cultures, cell lines and subcellular fractions Non-biological method : such as computer modelling, chemical interaction studies, receptor binding studies, … In vivo test method Test method using living (experimental) animals IP Integrated Project ITS Intelligent Testing Strategies IUCLID International Uniform Chemical Information Database JRC Joint Research Centre NCA Nationaal Centrum Alternatieven voor dierproeven (The Netherlands) NCP National Consensus Platform NGO Non-Governmental Organisation NO(A)EL No Observed (Adverse) Effect Level : the highest dose or exposure level within a specific test system, where no (adverse) treatment-related findings are observed OECD Organisation for Economic Co-operation and Development QSAR Quantitative Structure-Activity Relationship R&D Research & Development Read-across Endpoint information for one chemical is used to make a approach prediction of the endpoint for another chemical, which is considered to be similar RDN Reduced Data Need REACH Registration, Evaluation and Authorization of CHemicals RIP REACH Implementation Project SCCP Scientific Committee on Consumer Products SCENIHR Scientific Committee on Emerging and Newly Identified Health Risks SCHER Scientific Committee on Health and Environmental Risks SME Small and Medium-sized Enterprise SPORT Strategic Partnership on REACH Testing "Suitable" method A method that is sufficiently well developed according to internationally agreed test development criteria (e.g. the ECVAM criteria for the entry of a test into the prevalidation process) US EPA United States Environmental Protection Agency
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Valid method A technique that has not necessarily gone through the complete validation process, but for which sufficient scientific data exist demonstrating its relevance and reliability. Validated method A method for which the relevance and reliability are established for a particular purpose (in most cases according to the criteria established by ECVAM, taking into account that a prediction model needs to be present from the start of the validation procedure). These methods are taken up in Annex V to Directive 67/548/EEC (Dangerous Substances) and/or published as OECD Technical Guidelines*. VCI (German) Verband der Chemischen Industrie e.V. WG Working Group WWF World Wide Fund for Nature
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6. References
92/32/EEC - Council Directive 92/32/EEC of 30 April 1992 amending for the seventh time Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal L 154, 05/06/1992 p.1 . 1999/45/EC - Directive 1999/45/EC of the European Parliament and of the Council of 31 May 1999 concerning the approximation of the laws, regulations and administrative provisions of the Member States relating to the classification, packaging and labelling of dangerous preparations. Official Journal L 200, 30/07/1999 p.1 . Allanou R , Hansen B, van der Bilt Y (1999). Public Availability of Data on EU High Production Volume Chemicals. European Commission, DG JRC, IHCP, Document EUR 18996. Available through http://ecb.jrc.it/Data-Availability-Documents/datavail.pdf (consulted 17 February 2007). COM(2001) 88 final (2001) - White paper: Strategy for a future Chemicals Policy. Commission of the European Communities. Brussels, February 2001. COM(2003) 19 final (2003)- Third Report from the Commission to the Council and the European Parliament on the statistics on the number of animals used for experimental and other scientific purposes in the Member States of the European Union. Commission of the European Communities. Brussels, 22.01.2003. COM(2003) 644 final (2003) - Proposal for a Regulation of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency and amending Directive 1999/45/EC and Regulation (EC). Commission of the European Communities. Brussels, 29.10.2003. COM(2005) 7 Final (2005° - Fourth Report from the Commission to the Co uncil and the European Parliament on the Statistics on the number of animals used for experimental and other scientific purposes in the member states of the European Union. Available through http://ec.europa.eu/environment/chemicals/lab_animals/statistics_reports_en.htm (consulted 17 February 2007). CSTEE (Scientific Committee on Toxicity, Ecotoxicity and the Environment) (2004) Opinion of the Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE) on the BUAV-ECEAE report on "The way forward - action to end animal toxicity testing" Doc. C7/VR/csteeop/anat/08014 D(04), European Commission. EC 1907/2006 - Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. OJ L396, 1-849, 30 December 2006. EC 2006/C 276 E/01 - Common Position (EC) No 17/2006 adopted by the Council on 27 June 2006 with a view to adopting Regulation (EC) No …/2006 of the European Parliament and of the Council of… concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC of the European Parliament and of the Council and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. OJ C276E, 14 November 2006, 1-251. Greim H, Arand M, Autrup H, M. Bolt H, Bridges J, Dybing E, Glomot R, Foa V, Schulte-Hermann R (2006) Toxicological comments to the discussion about REACH. Arch.Toxicol. 80:121-124. Höfer T , Gerner I, Gundert-Remy U, Liebsch M, Schulte A, Spielmann H, Vogel R and Wettig K (2004). Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation. Arch Toxicol. 78(10):549-64.
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ICCG/1/06 - Inter Committee Coordination Group of Scientific Committees (ICCG) Position Statement “Alternatives to animal tests”. Adopted by the ICCG during the ICCG meeting of 3 July 2006 after consultation of each of the non-food Scientific Committees. IEH (Institute of Environment and Health) 2001a - Testing Requirements for Proposals under the EC White Paper ‘Strategy for a Future Chemicals Policy’ (Web Report W6), IEH, Leicester, UK, July 2001, available through http://www.silsoe.cranfield.ac.uk/ieh/pdf/w6.pdf (consulted 17 February 2007). IEH (Institute of Environment and Health) 2001b - Assessment of the feasibility of replacing current regulatory in vivo toxicity tests with in vitro tests within the framework specified in the EC White Paper ‘Strategy for an EU Chemicals Policy’ (Web Report 10), IEH, Leicester, UK, December 2001; available through http://www.silsoe.cranfield.ac.uk/ieh/pdf/w10.pdf (consulted 17 February 2007). JRC (Joint Research Centre) 2006 - Briefing note on number of animals expected to be used under reach summary of re-assessment performed by the JRC, October 2006, European Commission Directorate General JRC, Institute for Health and Consumer Protection, available through http://ihcp.jrc.ec.europa.eu/docs/ecb/REACHanimalfigures.pdf (consulted 17 February 2007). Pedersen F , de Bruijn J, Munn S & van Leeuwen K (2003). Assessment of additional testing needs under REACH – effects of (Q)SARs, risk based testing and voluntary industry initiatives. JRC Report EUR 20863 EN, available through http://ecb.jrc.it/DOCUMENTS/REACH/PUBLICATIONS/ (Consulted February 2007). SCCNFP/0834/04, Final (2004) - Opinion concerning "Report for establishing the timetable for phasing out animal testing for the purpose of the cosmetics directive" issued by ECVAM (30/04/2004), adopted by the SCCNFP on 1 July 2004 by means of the written procedure. van der Jagt K , Munn S, Tørsløv J and de Bruijn J (2004). Alternative approaches can reduce the use of test animals under REACH. JRC Report EUR 21405 EN, available through http://ecb.jrc.it/DOCUMENTS/REACH/PUBLICATIONS/ (Consulted February 2007).
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7. Appendices
Appendix A
Templates of Assessment Test Numbers of Studies
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CONAM Evaluation Templates
Endpoint in vivo Mutagenicity (OECD 474) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) 3 3 7 38 Available Data Scenario 97 97 93 62 (100 – available data %) Reduced Data Need Scenario (%) 23 23 22 15 Comments Available Data • Availability of data 1 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 37.89% (934) of 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 33.8% for “ mutagenicity ” in US HPV (US-EPA, 1998);
Reduced Data Needs • Principal source employed: Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 91% (US EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 74% of needs at >1 t/a will be meet by waiving; • Assumption that 74% of needs at >10 t/a will be meet by waiving; • Assumption that 71% of needs at >100 t/a will be meet by waiving; • Assumption that 47% of needs at >1000 t/a will be meet by waiving;; • Studies triggered by positive in vitro quantified as 45% based on ESR/OECD – assumes 30% for REACH; • EURAM 8% in vitro positives (1007 substances) and 35% in vivo positives (314 substances) ( Allanou et al., 1999 ); Overall Adequacy AD 2 2 2 1 Overall Adequacy RDN 2 2 2 2
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Endpoint Carcinogenicity (OECD 451) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA NA NA 44 Available Data Scenario NA NA NA 56 (100 – available data %) Reduced Data Need Scenario (%) NA NA NA 4 Comments NA Available Data
Reduced Data Needs • Principal source employed Pedersen et al. (2003) ; • Assumption that 0% of needs at >1000 t/a will be meet by QSAR/RA and 52% by waiving; • Requested for substances that are mutagenic category 3 (assume 30%) or causing concern based on repeat dose studies (assume 10%); Overall Adequacy AD NA NA NA 3 Overall Adequacy RDN NA NA NA 3
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Endpoint Skin Sensitisation LLNA Assay (OECD 429) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) 17 17 22 48 Available Data Scenario 83 83 78 52 (100 – available data %) Reduced Data Need Scenario (%) 37 37 34 23 Comments Available Data • Availability of data 1 – 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 48.32% (1,191) of 2,465 EU HPVCs ( Allanou et al., 1999 );
Reduced Data Needs • Principal source employed Pedersen et al. (2003); • Optimal use of QSAR/Grouping/RA for this endpoint 60% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 37% of needs at >1 t/a will be meet by QSAR/RA and 9% by waiving; • Assumption that 37% of needs at >10 t/a will be meet by QSAR/RA and 9% by waiving; • Assumption that 35% of needs at >100 t/a will be meet by QSAR/RA and 9% by waiving; • Assumption that 23% of needs at >1000 t/a will be meet by QSAR/RA and 6% by waiving; • Assumption of adaptation of test requirement due to physico-chemical properties within QSAR/RA evaluation – but toxicological properties not considered; Overall Adequacy AD 2 2 2 1 Overall Adequacy RDN 3 3 3 3
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Endpoint Acute Oral Toxicity, Acute toxic class method (OECD 423) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) 17 17 22 75 Available Data Scenario 83 83 78 25 (100 – available data %) Reduced Data Need Scenario (%) 9 9 8 0 Comments Available Data • Availability of data 1 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 76.96% (1,897) of 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 49.4% for “ acute toxicity ” in US HPV (US-EPA, 1998);
Reduced Data Need • Principal source employed: Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 92% (US EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption 1 – 10 t/a equivalent to 10 – 100 t/a (in CONAM model); • Assumption that 25% of needs at >10 t/a will be meet by QSAR/RA, 2% by waiving and 48% from “ promised ” data; • Assumption that 23% of needs at >100 t/a will be meet by QSAR/RA, 2% by waiving and 45% from “ promised ” data; • Assumption that 23% of needs at >1000 t/a will be meet by QSAR/RA, 0% by waiving and 2% from “ promised ” data; • Assumption that studies will not be conducted for substances that are corrosive or flammable – but not quantified; Overall Adequacy AD 2 2 2 1 Overall Adequacy RDN 3 3 3 3
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Endpoint Reproduction/Developmental Toxicity Screening Test (OECD 421) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 17 22 48 Available Data Scenario NA 83 78 52 (100 – available data %) Reduced Data Need Scenario (%) NA 18 17 0 Comments NA Available Data • Principal source employed Pedersen et al. (2003) • Availability of data 10 – 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability for “ developmental toxicity/teratogenicity ” 32% (789) of approx 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability for “ developmental/reproductive toxicity ” 22.8% in US HPV (US-EPA, 1998); • Annex X available data 48% inconsistent with 32% from EU HPVC;
Reduced Data Needs • Principal source employed: Pedersen et al. (2003); • Optimal use of QSAR/Grouping/RA for this endpoint 86% (cited US-EPA in Pedersen et al., 2003 ); • Assumption that 58% of needs at >10 t/a will be meet by QSAR/RA and 7% by waiving; • Assumption that 55% of needs at >100 t/a will be meet by QSAR/RA and 7% by waiving; • Assumption that 45% of needs at >1000 t/a will be meet by QSAR/RA and 7% from “promised ” data; • Assumption that the test is not required for 10% of cases >10 t/a where relevant human exposure is excluded for highly controlled substances; • Assumption that US HPV will cover all data for this endpoint for 1000 substances >1,000 t/a; Overall Adequacy AD NA 2 2 3 Overall Adequacy RDN NA 3 3 3
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Endpoint 2-Generation Reproductive Toxicity (OECD 416) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 3 7 26 Available Data Scenario NA 97 93 74 (100 – available data %) Reduced Data Need Scenario (%) NA 12 11 47 Comments NA Available Data • Availability of data 10 – 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 26% (641) for “ toxicity to reproduction ” of approx 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported 22.8% data availability for “ teratogenicity/reproductive toxicity ” in US HPV (US-EPA, 1998);
Reduced Data Needs • Principal source employed Pedersen et al. (2003) ; • Assumption that 0% of needs at >10 t/a will be meet by QSAR/RA and 85% by waiving; • Assumption that 0% of needs at >100 t/a will be meet by QSAR/RA and 82% by waiving; • Assumption that 0% of needs at >1000 t/a will be meet by QSAR/RA and 27% by waiving; • Assumption (not supported by specific information) that the test will be required after a positive result in 15% of repeated dose toxicity studies for >100 t/a; • Estimate for overall 80% data need for >1000 t/a substances based on assumption that 17% of HPVs are petroleum compounds classified as carcinogenic and will not require testing; Overall Adequacy AD NA 2 2 2 Overall Adequacy RDN NA 3 3 3
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Endpoint Developmental Toxicity (OECD 414) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 3 7 32 Available Data Scenario NA 97 93 68 (100 – available data %) Reduced Data Need Scenario (%) NA 10 57 37 Comments NA Available Data • Availability of data 10 – 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 32% (789) of approx 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 22.8% for “ teratogenicity/reproductive toxicity ” in US HPV (US-EPA, 1998);
Reduced Data Needs • Principal source employed Pedersen et al. (2003); • Optimal use of QSAR/Grouping/RA for this endpoint is 25% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 15% of needs at >10 t/a will be meet by QSAR/RA and 73% by waiving; • Assumption that 14% of needs at >100 t/a will be meet by QSAR/RA and 22% by waiving; • Assumption that 21% of needs at >1000 t/a will be meet by QSAR/RA and 10% by waiving; • Assumption (based on Reuter et al., 2003 ) that the test will be required after a positive result in 15% of developmental toxicity screening studies for >100 t/a; • Assumption that 90% of substances at >100 t/a will be tested; Overall Adequacy AD NA 2 2 1 Overall Adequacy RDN NA 3 3 3
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Endpoint Repeated Dose Toxicity: 28 Day Short Term Rodent Test (OECD 407) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 20 29 60 Available Data Scenario NA 80 71 40 (100 – available data %) Reduced Data Need Scenario (%) NA 17 13 0 Comments NA Available Data • IUCLID data availability for “ chronic toxicity ” 58.17% (1434) of approx 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported availability 13.9% for “ chronic toxicity ” in US HPV (US-EPA, 1998); • Assumption of distribution of 75% & 25% of substances for 28d and 90d tests at >100 t/a & >1000 t/a;
Reduced Data Needs • Principal source employed Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint is 92% (US EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 56% of needs at >10 t/a will be meet by QSAR/RA and 7% by waiving; • Assumption that 50% of needs at >100 t/a will be meet by QSAR/RA and 9% by waiving; • Assumption that 37% of needs at >1000 t/a will be meet by QSAR/RA and 3% from “promised ” data; • Assumption (not supported by specific information) that the test will not be required for 10% of substances at 10 - 100 t/a which are highly controlled and human exposure is excluded; Overall Adequacy AD NA 3 3 2 Overall Adequacy RDN NA 3 3 3
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Endpoint Repeated Dose Toxicity: 90 Day Subchronic Rodent Test (OECD 408) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 3 7 14 Available Data Scenario NA 97 93 86 (100 – available data %) Reduced Data Need Scenario (%) NA 6 13 12 Comments NA Available Data • Availability of data 10 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability for “ chronic toxicity ” 58.17% (1434) of approx 2,465 EU HPVCs ( Allanou et al., 1999 ); • Assumption of distribution of 75% & 25% of substances for 28d and 90d tests at >100 t/a & >1000 t/a; • Reported availability 13.9% for “ chronic toxicity ” in US HPV (US-EPA, 1998);
Reduced Data Needs • Principal source employed Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint is 40% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 68% of needs at >10 t/a will be meet by QSAR/RA and 23% by waiving; • Assumption that 28% of needs at >100 t/a will be meet by QSAR/RA and 52% by waiving; • Assumption that 26% of needs at >1000 t/a will be meet by QSAR/RA and 48% by waiving; • Assumption (not supported by specific information) that the test will not be required for 10% of substances 10-100 t/a which are highly controlled and human exposure is excluded; Overall Adequacy AD NA 3 3 2 Overall Adequacy RDN NA 3 3 3
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Endpoint Acute Eye Irritation/Corrosion (OECD 405) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 17 22 73 Available Data Scenario NA 83 78 28 (100 – available data %) Reduced Data Need Scenario (%) NA 11 11 2 Comments Available Data • Availability of data 10 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 72.9% (1,806) of 2,465 EU HPVCs ( Allanou et al., 1999 );
Reduced Data Need • Principal source employed: Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 40% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 11% of needs at >10 t/a will be meet by QSAR/RA, 5% by waiving and 48% by “ promised ” data; • Assumption that 10% of needs at >100 t/a will be meet by QSAR/RA, 5% by waiving and 45% by “ promised ” data; • Assumption that 2% of needs at >1000 t/a will be meet by QSAR/RA, 1% by waiving and 20% by “ promised ” data; Overall Adequacy AD NA 2 2 1 Overall Adequacy RDN NA 3 3 3
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Endpoint Acute Dermal Irritation/Corrosion (OECD 404) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 17 22 73 Available Data Scenario NA 83 78 28 (100 – available data %) Reduced Data Need Scenario (%) NA 11 11 2 Comments Available Data • Availability of data 10 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 73.27% (1,806) of 2,465 EU HPVCs ( Allanou et al., 1999 );
Reduced Data Need • Principal source employed: Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 80% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 21% of needs at >10 t/a will be meet by QSAR/RA, 3% by waiving and 48% by “ promised ” data; • Assumption that 20% of needs at >100 t/a will be meet by QSAR/RA, 3% by waiving and 45% by “ promised ” data; • Assumption that 4% of needs at >1000 t/a will be meet by QSAR/RA, 1% by waiving and 20% by “ promised ” data; Overall Adequacy AD NA 2 2 1 Overall Adequacy RDN NA 3 3 3
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Endpoint Acute Inhalation Toxicity (OECD 403) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 17 22 75 Available Data Scenario NA 83 78 25 (100 – available data %) Reduced Data Need Scenario (%) NA 20 19 0 Comments Available Data • Availability of data 10 – 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 50.75% (1,252) of 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 49.4% for “ acute toxicity ” in US HPV (US-EPA, 1998): • Annex X available data 75% inconsistent with 51% from EU HPVCs;
Reduced Data Needs • Principal source employed Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 92% (US EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 58% of needs at >10 t/a will be meet by QSAR/RA and 5% by waiving; • Assumption that 55% of needs at >100 t/a will be meet by QSAR/RA and 5% by waiving; • Assumption that 23% of needs at >1000 t/a will be meet by QSAR/RA and 2% from “promised ” data; • Assumption that studies will not be conducted for substances that are corrosive or flammable – but not quantified; Overall Adequacy AD NA 2 2 3 Overall Adequacy RDN NA 3 3 3
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Endpoint Acute Dermal Toxicity (OECD 402) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 17 22 73 Available Data Scenario NA 83 78 28 (100 – available data %) Reduced Data Need Scenario (%) NA 11 11 2 Comments Available Data • Availability of data 1 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 73.27% (1,806) of 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 49.4% for “ acute toxicity ” in US HPV (US-EPA, 1998); • Annex X available data 75% inconsistent with 53% from EU HPVCs;
Reduced Data Need • Principal source employed: Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 80% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 11% of needs at >10 t/a will be meet by QSAR/RA, 3% by waiving and 48% by “promised” data; • Assumption that 10% of needs at >100 t/a will be meet by QSAR/RA, 5% by waiving and 45% by “promised” data; • Assumption that 2% of needs at >1000 t/a will be meet by QSAR/RA, 1% by waiving and 20% by “promised” data; • QSAR/RA/waiving 1 – 10 t/a deemed equivalent to 10 – 100 t/a (in CONAM model); Overall Adequacy AD NA 2 2 3 Overall Adequacy RDN NA 3 3 3
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Endpoint Fish Bioaccumulation (OECD 305) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA NA 7 30 Available Data Scenario NA NA 93 86 (100 – available data %) Reduced Data Need Scenario (%) NA NA 12 9 Comments NA Available Data • Availability of data 100 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 29.94% (738) of approx 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 30.4% for “ ecotoxicity ” in US HPV (US-EPA, 1998);
Reduced data Needs • Principal source employed Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint is 80% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 18% of needs at >100 t/a will be meet by QSAR/RA and 63% by waiving; • Assumption that 13% of needs at >1000 t/a will be meet by QSAR/RA and 48% by waiving; • 60% of organic species Log Kow <3 so low potential for bioaccumulation (DK EPA, 2003 cited Pedersen et al., 2003 ); Overall Adequacy AD NA NA 2 1 Overall Adequacy RDN NA NA 2 2
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Endpoint Early Life Stage Fish Toxicity Test (OECD 210) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 3 7 14 Available Data Scenario NA 97 93 86 (100 – available data %) Reduced Data Need Scenario (%) NA 3 5 5 Comments NA Available Data • Availability of data 10 – 100 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 13.71% (338) of approx 2,465 EU HPVCs ( Allanou et al., 1999 );
Reduced Data Needs • Principal source employed Pedersen et al. (2003); • Optimal use of QSAR/Grouping/RA for this endpoint is 45% (DK EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 29% of needs at >10 t/a will be meet by QSAR/RA and 65% by waiving; • Assumption that 28% of needs at >100 t/a will be meet by QSAR/RA and 60% by waiving; • Assumption that 26% of needs at >1000 t/a will be meet by QSAR/RA and 55% by waiving; • Assumption that 5% of substances at <100 t/a and 10% at >100t/a will be tested; Overall Adequacy AD NA 2 2 1 Overall Adequacy RDN NA 3 3 3
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Endpoint Chronic Bird Toxicity (OECD 206) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA NA NA 1 Available Data Scenario NA NA NA 99 (100 – available data %) Reduced Data Need Scenario (%) NA NA NA 1 Comments NA Available Data
Reduced data Needs • Principal source employed Pedersen et al. (2003) ; • Assumption that 99% of potential needs at >1000 t/a will be meet by waiving; Overall Adequacy AD NA NA NA 3 Overall Adequacy RDN NA NA NA 3
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Endpoint Acute Toxicity in Fish (OECD 203) Annex Annex VII Annex VIII Annex IX Annex X Tonnage Band 1 – 10 t 10 – 100 t 100 – 1000 t >1000 t Available Data (%) NA 17 22 62 Available Data Scenario NA 83 78 38 (100 – available data %) Reduced Data Need Scenario (%) NA 14 13 0 Comments Available Data • Availability of data 10 - 1000 t/a based on survey of associations/manufacturers by RPA & Statistics Sweden 2002 (cited in Pedersen et al., 2003 ); • IUCLID data availability 67.95% (1,675) of 2,465 EU HPVCs ( Allanou et al., 1999 ); • Reported data availability 30.4% for “ ecotoxicity ” in US HPV (US-EPA, 1998);
Reduced Data Needs • Principal source employed Pedersen et al. (2003) ; • Optimal use of QSAR/Grouping/RA for this endpoint 85% (US EPA, 2003 cited in Pedersen et al., 2003 ); • Assumption that 41% of needs at >10 t/a will be meet by QSAR/RA, 4% by waiving and 24% from “ promised ” data; • Assumption that 39% of needs at >100 t/a will be meet by QSAR/RA, 3% by waiving and 22% from “ promised ” data; • Assumption that 33% of needs at >1000 t/a will be meet by QSAR/RA, 0% by waiving and 5% from “ promised ” data; Overall Adequacy AD NA 2 2 1 Overall Adequacy RDN NA 3 3 3
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Appendix B
Listing of issues addressed in ecopa workshops on REACH and SCALE
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2005
Presentations of the 6 th ecopa Annual Meeting 2005 Brussels, Sheraton Airport, December 17-18, 2005
Subject/Issue Title Presenter Stephane Hogan, Head of Unit - "New technology and Applied Genomics & Biotechnology, FP 7 competitiveness" Health Directorate, DG Research, European Commission "New Technologies: Threat or Bernward Garthoff, DVM, Bayer New Technologies and Alternative Chance for Alternative Method CropScience AG, Monheim, Methods Development" Germany Thomas Hartung & ECVAM Team, "ECVAM efforts in nano- and Test Programmes/Validation Institute for Health and Consumer biotechnology" Protection (IHCP), Ispra (Va), Italy Horst Spielmann, National German Centre for the Documentation and Evaluation of Alternative Methods Project ReProTect "Integrated Project ReProTect" to Animal Experiments (ZEBET), Federal Institute for Risk Assessment (BfR), Berlin, Germany Cecilia Clemedson, Scientific ACuteTox Project "ACuteTox - IP EU 6FP" Coordinator, Expertradet, Sweden "Conam: Activities within Conam Vera Rogiers, Dept. of Toxicology, CONAM Project project" Vrije Universiteit Brussel, Belgium Erwin L. Roggen, Science "Novel Testing Strategies for In Testing Allergens Manager, Immunology, Novozymes Vitro assessment of Allergens" AS "Optimisation of liver and intestine Pharmacokinetics and – dynamics Flavia Zucco, LIINTOP - LIver, in vitro models for pharmacokinetic in vitro INTestine OPtimisation, Italy and pharmacodynamic studies" "Carcinogenomics - Development of Joost van Delft, Dept. of Health a high throughput genomics-based Risk Analysis & Toxicology, Carcinogenomics Project test for assessing genotoxic and Maastricht University, carcinogenic properties of chemical The Netherlands compounds in vitro "
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2004
Presentations of the 5 th ecopa Annual Meeting 2004 Sheraton Airport Brussels, Belgium, November 26 - 28, 2004
Subject/Issue Title Presenter "Impact of ‘European legislation on Yvon Slingenberg, Dep. Head European Safety Legislation Europe's consumer safety, Chemicals Unit, DG Environment, B environment and competitiveness" SCALE it right: animal testing vs. New Technologies and Animal Bernward Garthoff, Bayer alternative method development for Experiments in SCALE CropScience AG, Monheim, D human health Endocrine disrupting chemicals: Poul Bjerregaard, University of S. Endocrine disruption testing What can we learn from the use of Denmark, Odense, DK nonmammalian tests? Which overlaps of SCALE do exist Lucianne Licari, Reg. Adv., WHO- SCALE, REACH Overlap with CEHAPE, REACH etc.: The Reg. Office EU, I Budapest results Existing OECD-guidelines and Drew Wagner,OECD, Principal OECD-Guidelines those underway on a global scale Administrator, Paris, F Validated methods and Thomas Hartung, ECVAM, JRC Validated Methods methodology currently validated by Ispra, I ECVAM in this area View of Academia: The view of academia and Lisbeth Knudsen, University of on Alternative Methods environmental organisations Copenhagen, DK Marylou Heinen, Eurogroup for View Animal Welfare The view of animal welfare Animal Welfare, Brussels, B Gernot Klotz, Bayer AG, View of Industry The view of the industry Leverkusen, D
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2003
Presentations of the 4 th ecopa Annual Meeting 2003 Sheraton Airport Hotel, Brussels, November 29 - 30, 2003
Subject/Issue Title Presenter Abraao Carvalho, DG Enterprise, EC-Support for Alternatives Opening address Head of Unit F3, DG ENT, BE Basic Research and Development Bernward Garthoff, Treasurer Basic Research in Alternatives Work on Alternative Methods: We ecopa , Bayer CropScience, are falling short of News! Monheim, D Running European Pre- and Thomas Hartung, ECVAM, DG Pre- and Validation Pipeline Validation-Studies, Pipeline and JRC, I Future Impact Hermann Koëter, former Princ. Other Alternatives in the Making on Administrator, Environment Alternative Guidelines OECD a worldwide Basis, Summary of the Directorate, OECD, presently: Dep. OECD Exec. Dir./ Dir. Of Science, EFSA, Brussels, B Does the Set-Up of the EU 6 th Framework Programme help to Beatrice Lucaroni, Sci. Off., Set-up of 6 th FP address the need for new DG RTD, B/EU approaches? ecopa -initiated projects resp. José Castell, Vice president ecopa , projects with ecopa -participation Valencia,E
- Predictomics (José Castell, E) Projects in the 6 th FP - CONAM (Vera Rogiers, B) - Reprotect (Introduction) (Thomas Hartung, I & Rita Cortvindt, B) - SensaCellTox (David Cowell, UK) - Edit (Cecilia Clemedson, S) Genotoxicity testing in vitro . The Novel Approaches in Genotox Nicola Loprieno, Pisa, I future for oxidative hair dyes Cosmetics Cosmetic Industry Odile de Silva, Paris, F Academia Academia Peter Maier, Münsingen, CH IVTIP IVTIP & National Platforms Joan-Albert Vericat, Madrid, E Alternative Non-Animal Testing and Skin in-vitro -Testing Tissue Models Bart De Wever, Nice, F Risk Assessment: CSTEE Joint Non-animal Testing and Risk Working Group on Alternative Non- Erik Dybing, Oslo, N Assessment Animal Testing Funding vs. Politics” - Are we on the right track to “REACH the Tom Feijtel, Procter&Gamble, Funding station” of Cosmetics Guideline and London , UK EU Chemical Policy without animal testing?
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2002
Presentations of the 3 rd ecopa Annual Meeting 2002 Sheraton Airport Hotel, Brussels, November 08-10, 2002
Subject/Issue Title Presenter J. Tavernier, Belgian Minister for National Guidelines Opening Consumer Protection, Public Health and Environment, BE Development of Guidelines: Policies and Technical Procedure: H. Koëter(c), Princ. Administrator, OECD Process for Guidelines on Slow Process at OECD? Environment Directorate, OECD, Alternatives Approaches by New Testing Paris, F Strategies vs. Validation Guidelines for Alternatives: Does it Process for Alternative Methods B. Garthoff, ecopa working group, Require Decades? The Need for Acceptance BCS AG, D Research! View of the Animal Welfare M. L. Stephens (c), Secretariate of Animal Welfare View Associations / ICAPO ICAPO, USAD, USA Industrial Toxicology View View of an Industrial Toxicologist D. Esdaile (c), ECETOC, F View of a Governmental Institution Governmental Institution View H. Spielmann, Zebet, D for Implementation of Alternatives View of a National Coordinator: D. Blakey, Environmental Health National OECD-Coordinator View Canada Science, Ontario, CND J. Küllmer, German federal Ministry Out of the View of the Authority for the Environment, Nature Authorities Governing the National Coordinator Conservation and Nuclear Safety, D Governmental View: State’s National State Involvement E. Bengtsson, KemI, S Involvement: Sweden The Scientific View: Alternatives to be Introduced 6th Framework Programme: Follow- B. Lucaroni, Sci. Off. DG Research, Science Commission View up on the Commission B/EU Stakeholders Meeting of 9-10 July, Brussels Small Scale Pre-validation Studies in Industry: The Way Forward P. Vanparys, Johnson & Johnson New Test Methods Proposal for the Reduction of PR&D, B Animal Use in Routine in vivo Micronucleus Testing Speeding up Implementation of Speeding up Process of Alternative Methods in OECD and O. de Silva, L’Oréal, F Implementation other worldwide guidelines: Ideas for a speedy process
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2001
Presentations of the 2 nd ecopa Annual Meeting 2001 Sheraton Airport Hotel, Brussels, October 27 - 28, 2001
Subject/Issue Title Presenter M. Aelvoet, Belgian Minister for Country Support for Alternatives Opening Consumer Protection, Public Health and Environment, B The Whitebook Strategy for a G. Vogelgesang, The Chemical Whitebook Future Chemical Policy: Intentions DG Environment, B of the Commission The European Whitebook on chemicals: Start into an Area of B. Garthoff, ecopa working group, The Chemical Whitebook Alternatives to Animal BCS AG, D Experimentation ? View of the (European) Chemical The Chemical Whitebook R. Taalman, CEFIC, B Industry and CEFIC View of the Animal Welfare U. Sauer, EUROGROUP for Animal The Chemical Whitebook Associations Welfare, D The Chemical Whitebook View of a Toxicologist Ph. Botham, ECETOC, UK View of an Institution for The Chemical Whitebook H. Spielmann, Zebet, D Implementation of Alternatives J. Huggard, Chemical Policy View of Environmental Associations Weinberg Consultants, B A governmental View: Torn E. Sandberg, Ministry of Chemical Policy between Environmental Concern Environment, S and Lab Animal Death ? Possibilities for prescreening Pre-screening E. Walum, Stockholm University, S alternatives In silico prediction of harmful effects In silico A. Vedani, CH triggered by chemicals Podium Discussion: The Way The new EU Chemical Policy L. Bansil, P&G, UK Forward ?
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Appendix C
Short comment on the CONAM report “the Impact of REACH”, March 2007 from an animal welfare point of view
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Some comments on the report from an animal welfare point of view: by Roman Kolar, ecopa Board member, Deutscher Tierschutzbund 19 March 2007.
Already in the course of the legislative procedure of the EU REACH Regulation, animal welfare organisations made clear that they did not consider an increase in research animal use to be unavoidable or necessary to ensure that human health and environmental protection are adequately met by the new chemicals legislation. Furthermore, they revealed numerous ways and initiatives to be taken up in order to avoid animal testing for the purposes of REACH.
It is against this background that from an animal welfare perspective the CONAM report “The impact of REACH” of March 2007 does not adequately address means that are available to overcome the foreseen increase in animal use under the REACH system. Moreover, for instance, the estimations in the CONAM report concerning the selection of “suitable methods”, the contributions that in silico , read across or in vitro methodologies can make in reducing animal use under REACH and the CONAM report’s estimation of the role of ECVAM in this context do not seem appropriate from an animal welfare point of view.
Furthermore a critical evaluation of the scientific relevance and reliability of animal test methods necessary for an objective estimation of the likely impact of REACH is lacking in the CONAM report. However such a balanced evaluation would be necessary in determining appropriate testing methods aiming at scientifically sound risk assessment and risk management measures.
Finally, the position taken in the CONAM report in regard to the impact of the stakeholder commenting period to testing proposals laid down in the REACH Regulation clearly contradicts the position animal welfare organisations have repeatedly expressed in this context.
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